Unlocking the Power of Modern Therapeutic Regimens for Prostate Cancer: Experts Put the Pressure on Key Evidence and Real-World Strategies to Optimize Patient Care
PeerView
17 views
93 slides
Jun 20, 2024
Slide 1 of 93
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
About This Presentation
Chair and Presenters, Karim Fizazi, MD, PhD, Pedro C. Barata, MD, MSc, FACP, Kim N. Chi, MD, FRCPC, and Alicia K. Morgans, MD, MPH, discuss prostate cancer in this CME/MOC/NCPD/AAPA/IPCE activity titled “Unlocking the Power of Modern Therapeutic Regimens for Prostate Cancer: Experts Put the Pressu...
Slide Content
Unlocking the Power of Modern Therapeutic
Regimens for Prostate Cancer
Experts Put the Pressure on Key Evidence and
Real-World Strategies to Optimize Patient Care
Karim Fizazi, MD, PhD
Professor of Medicine
GETUG President
Department of Cancer Medicine
Institut Gustave Roussy
University of Paris Saclay
Villejuif, France
Pedro C. Barata, MD, MSc, FACP
Miggo Family Chair in Cancer Research
Co-Leader Genitourinary (GU) Disease Team
Director of GU Medical Oncology Research Program JB
University Hospitals Seidman Cancer Center
Associate Professor of Medicine
Case Western Reserve University
Case Comprehensive Cancer Center
Cleveland, Ohio
2
Kim N. Chi, MD, FRCPC
BC Cancer
Vancouver Prostate Centre
University of British Columbia
Vancouver, British Columbia, Canada
Alicia K. Morgans, MD, MPH
Associate Professor of Medicine
Harvard Medical School
Medical Director, Survivorship Program
Dana-Farber Cancer Institute
Boston, Massachusetts
Go online to access full CME/MOC/NCPD/AAPA/IPCE information, including faculty disclosures.
Copyright © 2000-2024, PeerView
El
Regimens for Prostate Cancer
Experts Put the Pressure on Key Evidence and
Real-World Strategies to Optimize Patient Care
Karim Fizazi, MD, PhD
Professor of Medicine
GETUG President
Department of Cancer Medicine
Institut Gustave Roussy
University of Paris Saclay
Villejuif, France
Pedro C. Barata, MD, MSc, FACP
Miggo Family Chair in Cancer Research
Co-Leader Genitourinary (GU) Disease Team
Director of GU Medical Oncology Research Program JB
University Hospitals Seidman Cancer Center
Associate Professor of Medicine
Case Western Reserve University
Case Comprehensive Cancer Center
Cleveland, Ohio
2
Kim N. Chi, MD, FRCPC
BC Cancer
Vancouver Prostate Centre
University of British Columbia
Vancouver, British Columbia, Canada
Alicia K. Morgans, MD, MPH
Associate Professor of Medicine
Harvard Medical School
Medical Director, Survivorship Program
Dana-Farber Cancer Institute
Boston, Massachusetts
Go online to access full CME/MOC/NCPD/AAPA/IPCE information, including faculty disclosures.
Copyright © 2000-2024, PeerView
El
PeerView.com/YWU827
Our Goals for Today
Augment your understanding of the rationale and evidence for
modern treatment options in the management of patients with
prostate cancer
Equip you with strategies for incorporating various therapeutic
regimens into management plans
Provide guidance on how to mitigate and manage treatment-related
AEs and educate patients to optimize outcomes
Our Goals for Today
Augment your understanding of the rationale and evidence for
modern treatment options in the management of patients with
prostate cancer
Equip you with strategies for incorporating various therapeutic
regimens into management plans
Provide guidance on how to mitigate and manage treatment-related
AEs and educate patients to optimize outcomes
Peer Pressure Rules
Competing in the challenge!
+ The first to hit the buzzer will have a chance to answer
+ Faculty contestants who answer correctly will receive 100 points
« Faculty contestants who answer incorrectly will lose 100 -
+ If a contestant answers incorrectly, the other contestants have a chance to
steal for 100 points
PeerView.com/YWU827
Competing in the challenge!
+ The first to hit the buzzer will have a chance to answer
+ Faculty contestants who answer correctly will receive 100 points
« Faculty contestants who answer incorrectly will lose 100 -
+ If a contestant answers incorrectly, the other contestants have a chance to
steal for 100 points
PeerView.com/YWU827
Prostate Cancer Challenge
What year was the first ASCO annual meeting held?
1. 1988
1968
1974
1964
PeerView.com/YWU827
What year was the first ASCO annual meeting held?
1. 1988
1968
1974
1964
PeerView.com/YWU827
Prostate Cancer Challenge
What was the HR for MFS in the phase 3 EMBARK trial demonstrating the
benefit of combination therapy over LHRH monotherapy for patients with
nmHSPC?
0.42
0.51
0.73
0.88
PeerView.com/YWU827
What was the HR for MFS in the phase 3 EMBARK trial demonstrating the
benefit of combination therapy over LHRH monotherapy for patients with
nmHSPC?
0.42
0.51
0.73
0.88
PeerView.com/YWU827
Focus on Localized Prostate Cancer
and Biochemical Recurrence
Alicia K. Morgans, MD, MPH
Associate Professor of Medicine
Harvard Medical School
Medical Director, Survivorship Program
Dana-Farber Cancer Institute
Boston, Massachusetts
Copyright © 2000-2024, Peerview
and Biochemical Recurrence
Alicia K. Morgans, MD, MPH
Associate Professor of Medicine
Harvard Medical School
Medical Director, Survivorship Program
Dana-Farber Cancer Institute
Boston, Massachusetts
Copyright © 2000-2024, Peerview
Defining High-Risk Localized and
Locally Advanced Prostate Cancer!
Patterns of Presentation Increased Mortality in
High-Risk Prostate Cancer
nigh tek High-Risk Feature 15-Year PCSM, %
Intermediate risk PSA >20 ng/mL 22
Gleason 8-10 34
a cT3 E
Regional High-risk disease 19
Cancer Diagnoses, %
o3883882388
+ Patients with high-risk disease have an increased risk of biochemical recurrence (BCR),
metastases, and death from prostate cancer
* 20% to 40% of patients with high-risk localized disease who undergo RP and/or RT
develop BCR
1. Cooperberg MR etal. J Cin Oncol, 2010:28:1117-1123. 2. MeKay RR etal Am Soe Cin Oncol Educ Book. 2020:40:1-1. 3, Taplin ME, ASCO GU 2022. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
Locally Advanced Prostate Cancer!
Patterns of Presentation Increased Mortality in
High-Risk Prostate Cancer
nigh tek High-Risk Feature 15-Year PCSM, %
Intermediate risk PSA >20 ng/mL 22
Gleason 8-10 34
a cT3 E
Regional High-risk disease 19
Cancer Diagnoses, %
o3883882388
+ Patients with high-risk disease have an increased risk of biochemical recurrence (BCR),
metastases, and death from prostate cancer
* 20% to 40% of patients with high-risk localized disease who undergo RP and/or RT
develop BCR
1. Cooperberg MR etal. J Cin Oncol, 2010:28:1117-1123. 2. MeKay RR etal Am Soe Cin Oncol Educ Book. 2020:40:1-1. 3, Taplin ME, ASCO GU 2022. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
Unmet Needs in Localized Disease
Downloadable
Resources
10 years following definitive therapy, 20%-50% of patients experience
disease recurrence characterized by rising PSA levels!
Limited level 1 clinical data exist for the treatment of patients with BCR
Patients with high-risk BCR are at increased risk
of prostate cancer-specific mortality?
Evidence from phase 3 clinical trials demonstrated that
treatment intensification with ARSI consistently improved patient
outcomes across the prostate cancer continuum*?
1. Kupelan PA et al. Cancer 2002:95.2302-2307. 2 Kupelan PA et al. Urology. 2006:68:503-508. 3. Freecland Set al. JAMA. 2005:204:433-430,
4. Freediand SJ et al. J Cin Oncol, 2007:25:1765-1771. 6, Markowski MC et al in Gentourin Cancer. 2019.17:470-471, 6. Scher Hl et a. N Engl Med.
2012:367:1187-1107. 7. Beer TM eta N Eng J Med, 2014:371:424-433, 8, Hussain M et al N Eng! J Med. 2018;378:2465-2474, 9, Armstrong Al etal. A
‘I Gin Oncol 2019;37-2974-2986. 10. Davis ID et al. N Engl J Med, 2019,381:121-131. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Downloadable
Resources
10 years following definitive therapy, 20%-50% of patients experience
disease recurrence characterized by rising PSA levels!
Limited level 1 clinical data exist for the treatment of patients with BCR
Patients with high-risk BCR are at increased risk
of prostate cancer-specific mortality?
Evidence from phase 3 clinical trials demonstrated that
treatment intensification with ARSI consistently improved patient
outcomes across the prostate cancer continuum*?
1. Kupelan PA et al. Cancer 2002:95.2302-2307. 2 Kupelan PA et al. Urology. 2006:68:503-508. 3. Freecland Set al. JAMA. 2005:204:433-430,
4. Freediand SJ et al. J Cin Oncol, 2007:25:1765-1771. 6, Markowski MC et al in Gentourin Cancer. 2019.17:470-471, 6. Scher Hl et a. N Engl Med.
2012:367:1187-1107. 7. Beer TM eta N Eng J Med, 2014:371:424-433, 8, Hussain M et al N Eng! J Med. 2018;378:2465-2474, 9, Armstrong Al etal. A
‘I Gin Oncol 2019;37-2974-2986. 10. Davis ID et al. N Engl J Med, 2019,381:121-131. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Role of Treatment Intensification in the
High-Risk Localized/Locally Advanced Setting
Combining ADT with docetaxel or second-generation hormone treatment (abiraterone,
apalutamide, or enzalutamide) improves outcomes in metastatic prostate cancer
Has treatment intensification changed the standard of care in the high-risk
localized/locally advanced setting?
STAMPEDE Meta-Analysis!
Analyzed new data from two randomized controlled phase 3 trials from a multi-arm,
multistage platform protocol to assess SOC (radiation therapy + 3 y of ADT) with SOC +
abiraterone acetate + prednisolone + enzalutamide for 2 y in the nonmetastatic,
high-risk MO patient population, as defined by conventional imaging
Results showed that patients with high-risk nonmetastatic prostate cancer who received ADT +
combination therapy had significantly better MFS and OS than those who received ADT alone
Takeaway: 2 years of abiraterone and prednisolone added to ADT and, if indicated,
radiotherapy is a potential new standard treatment for nonmetastatic prostate cancer with
high-risk features
1.Atard G et al. Lancet 2022:300:447-400. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
High-Risk Localized/Locally Advanced Setting
Combining ADT with docetaxel or second-generation hormone treatment (abiraterone,
apalutamide, or enzalutamide) improves outcomes in metastatic prostate cancer
Has treatment intensification changed the standard of care in the high-risk
localized/locally advanced setting?
STAMPEDE Meta-Analysis!
Analyzed new data from two randomized controlled phase 3 trials from a multi-arm,
multistage platform protocol to assess SOC (radiation therapy + 3 y of ADT) with SOC +
abiraterone acetate + prednisolone + enzalutamide for 2 y in the nonmetastatic,
high-risk MO patient population, as defined by conventional imaging
Results showed that patients with high-risk nonmetastatic prostate cancer who received ADT +
combination therapy had significantly better MFS and OS than those who received ADT alone
Takeaway: 2 years of abiraterone and prednisolone added to ADT and, if indicated,
radiotherapy is a potential new standard treatment for nonmetastatic prostate cancer with
high-risk features
1.Atard G et al. Lancet 2022:300:447-400. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Phase 3 Clinical Trials for High-Risk Prostate Cancer
Trial Patients, N Treatment
Apalutamide + ADT vs
placebo + ADT
EBRT + ADT + enzalutamide vs
PROTEUS! 2,000
ENZARAD? B02 EBRT + ADT + NSAA
ss vas unes
DASL-HiCaP* 1,100 as
PEACE wee Geneseo gee
er He eee PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Trial Patients, N Treatment
Apalutamide + ADT vs
placebo + ADT
EBRT + ADT + enzalutamide vs
PROTEUS! 2,000
ENZARAD? B02 EBRT + ADT + NSAA
ss vas unes
DASL-HiCaP* 1,100 as
PEACE wee Geneseo gee
er He eee PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Neoadjuvant Trials: Phase 3 PROTEUS"
Apalutamide + ADT Versus Placebo + ADT in the Neoadjuvant Setting for Patients With Localized or
Locally Advanced and High-Risk Prostate Cancer
Sos 6-Month Neoadjuvant An 6-Month Neoadjuvant Post
Treatment (Cycles 1-6) Treatment (Cycles 7-12) Treatment
m + PSA levels monitored
Patients APA 240 mg RP with PLND APA 240 mg every 3 mo for BCF
+ Localized or locally QD + ADT + Conventional imaging
advanced, high risk/ at BCF and then every
very high-risk PC 6 mo until distant
+ Candidates for RP PBO + ADT PBO + ADT metastasis on
with PLND conventional imaging
,000) or death
+ Conventional imaging + PSAtesting and + Conventional imaging + Adjuvant or + PSMA-PET imaging at
(CT or MRI and radiological within 4 wk after RP salvageradiation 3-mo post-adjuvant
bone scan) assessment for + Cardiovascular and therapy post RP treatment, at BCF,
+ Cardiovascular and progression thrombotic risk at investigator's and every 6 mo until
thrombotic risk assessment priorto discretion distant metastasis on
assessment and after RP PSMA-PET or
conventional imaging
+ Primary endpoints: pCR rate and MFS oedeath
1. Kibel AS et al ASCO GU 2022. Abstract TPS285. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
Apalutamide + ADT Versus Placebo + ADT in the Neoadjuvant Setting for Patients With Localized or
Locally Advanced and High-Risk Prostate Cancer
Sos 6-Month Neoadjuvant An 6-Month Neoadjuvant Post
Treatment (Cycles 1-6) Treatment (Cycles 7-12) Treatment
m + PSA levels monitored
Patients APA 240 mg RP with PLND APA 240 mg every 3 mo for BCF
+ Localized or locally QD + ADT + Conventional imaging
advanced, high risk/ at BCF and then every
very high-risk PC 6 mo until distant
+ Candidates for RP PBO + ADT PBO + ADT metastasis on
with PLND conventional imaging
,000) or death
+ Conventional imaging + PSAtesting and + Conventional imaging + Adjuvant or + PSMA-PET imaging at
(CT or MRI and radiological within 4 wk after RP salvageradiation 3-mo post-adjuvant
bone scan) assessment for + Cardiovascular and therapy post RP treatment, at BCF,
+ Cardiovascular and progression thrombotic risk at investigator's and every 6 mo until
thrombotic risk assessment priorto discretion distant metastasis on
assessment and after RP PSMA-PET or
conventional imaging
+ Primary endpoints: pCR rate and MFS oedeath
1. Kibel AS et al ASCO GU 2022. Abstract TPS285. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
Phase 3 ATLAS: Apalutamide Plus ADT in High-Risk
Localized or Locally Advanced Prostate Cancer’
Apalutamide + ADT + RT Treatment Phase: 28-Day Cycles + 2 Days
Screening (<35 days) Neoadjuvant to RT Concurrent with RT Adjuvant to RT
(Cycles 1-2) (Cycles 3-4) (Cycles 5-30)
Key Eligibility Criteria 2 RT with APA sae
+ High-risk localized prostate ‘APA 240 mg QD + 240 mg QD + [oie
cancer bicalutamide-PBO + eee
+ ECOG PS 0-1 GnRH agonist pole
+ Charlson index <3
+ Candidates for primary RT RT with PBO +
+ No distant metastasis, history bicalutamide +
of bilateral orchiectomy, pelvic i SnRH agon GnRH
radiation, or seizure
PSA and testosterone testing for BCF
Conventional imaging Conventional and PET imaging initiated at BCF
+ Long-term follow-up
= PSA and testosterone levels monitored every 3 months until distant metastasis by BICR
= Conventional imaging every 6 months until distant metastasis by BICR or death
— PET imaging every 6 months until distant metastasis on PET or conventional imaging by BICR or death
+ Primary endpoint: MES
1. ps ww incl govstudyINCTO2S31516. 2, Sandler HM et al, ASCO 2022. Abstract 5084. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
Localized or Locally Advanced Prostate Cancer’
Apalutamide + ADT + RT Treatment Phase: 28-Day Cycles + 2 Days
Screening (<35 days) Neoadjuvant to RT Concurrent with RT Adjuvant to RT
(Cycles 1-2) (Cycles 3-4) (Cycles 5-30)
Key Eligibility Criteria 2 RT with APA sae
+ High-risk localized prostate ‘APA 240 mg QD + 240 mg QD + [oie
cancer bicalutamide-PBO + eee
+ ECOG PS 0-1 GnRH agonist pole
+ Charlson index <3
+ Candidates for primary RT RT with PBO +
+ No distant metastasis, history bicalutamide +
of bilateral orchiectomy, pelvic i SnRH agon GnRH
radiation, or seizure
PSA and testosterone testing for BCF
Conventional imaging Conventional and PET imaging initiated at BCF
+ Long-term follow-up
= PSA and testosterone levels monitored every 3 months until distant metastasis by BICR
= Conventional imaging every 6 months until distant metastasis by BICR or death
— PET imaging every 6 months until distant metastasis on PET or conventional imaging by BICR or death
+ Primary endpoint: MES
1. ps ww incl govstudyINCTO2S31516. 2, Sandler HM et al, ASCO 2022. Abstract 5084. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
Adjuvant Trial: Phase 3 DASL-HiCaP*2
Darolutamide + ADT + RT
Key Eligibility Criteria
+ Very high-risk localized prostate Stratification
Darolutamide 600 mg
cancer to be treated with definitive + Previous RP (yes twice daily +
radiation or very high-risk features + or no) ADT x 96
PSA persistence/rise within 12 mo + Planned docetaxel
following RP to be treated with post- use (yes or no)
RP radiation + Clinical or
+ Suitable for EBRT + brachytherapy pathological pelvic
+ CT/MRI and bone scan negative for LN involvement (yes
distant metastases (allow pelvic LN) or no)
N= 1,100
+ Primary endpoint: MFS
+ Secondary endpoints: OS, prostate cancer-specific survival, PSA-progression free survival, time to
subsequent hormonal therapy, time to castration resistance, frequency and severity of AEs, health-related
QOL, fear of cancer recurrence
+ Exploratory endpoints: incremental cost effectiveness, prognostic/predictive biomarkers
"Al participants are also treated concurrent wit an LHRH agonist for 98 weeks post randomization, plus RT string at week 8-24 post randomization. u
1. Nazi T etal ASCO 2022. Abstract 155103. 2. htps/lnialias govlstudyNCTO436353. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
Darolutamide + ADT + RT
Key Eligibility Criteria
+ Very high-risk localized prostate Stratification
Darolutamide 600 mg
cancer to be treated with definitive + Previous RP (yes twice daily +
radiation or very high-risk features + or no) ADT x 96
PSA persistence/rise within 12 mo + Planned docetaxel
following RP to be treated with post- use (yes or no)
RP radiation + Clinical or
+ Suitable for EBRT + brachytherapy pathological pelvic
+ CT/MRI and bone scan negative for LN involvement (yes
distant metastases (allow pelvic LN) or no)
N= 1,100
+ Primary endpoint: MFS
+ Secondary endpoints: OS, prostate cancer-specific survival, PSA-progression free survival, time to
subsequent hormonal therapy, time to castration resistance, frequency and severity of AEs, health-related
QOL, fear of cancer recurrence
+ Exploratory endpoints: incremental cost effectiveness, prognostic/predictive biomarkers
"Al participants are also treated concurrent wit an LHRH agonist for 98 weeks post randomization, plus RT string at week 8-24 post randomization. u
1. Nazi T etal ASCO 2022. Abstract 155103. 2. htps/lnialias govlstudyNCTO436353. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
Phase 3 EMBARK: Enzalutamide Plus Leuprolide Acetate’
Week 37
Key Eligibility Criteria Enzalutamide 160 mg oral QD +
+ Screening PSA 21 ng/mL after RP leuprolide acetate 2 5 mg IM Q12W = Suspend
and 22 ng/mL above the nadir for (n= 355 8
primary EBRT Blinded 3 ene
+ PSADT <9 mo Placebo + E nitor PSA
+ No metastases on bone scan or CT/MRI e de mentor
ad leuprolide acetate 22.5 mg IN É (reinitiate if
+ Testosterone 2150 ng/dL El nad El PSA rises)®
+ Prior hormonal therapy 29 mo prior to 3
RT (neoadjuvant/adjuvant for 536 mo Y
OR <6 mo for rising PSA) Enzalutamide 160 mg oral QD < Remain on
2
treatment
N= 1,068 Unblinded
Stratification: screening PSA (s10 ng/mL vs >10 ng/mL), PSADT (<3 mo vs >3 to <9 mo), prior hormonal therapy (yes vs no)
Primary endpoint®: MFS by BICR (enzalutamide + leuprolide acetate vs leuprolide acetate)
Key secondary endpoints®“; MFS by BICR (enzalutamide vs leuprolide acetate), time to PSA progression, time to first use of new antineoplastic
therapy, OS*
+ Other secondary endpoints: safety, PRO
+ study tenen was suspended once a week 37 PSA was <02 nom and restated when PSA vas 250 np. (tout pot RP) and 22 nio RP). IT population. Prima
(np and key secondary endpont e eneaisamide combina and enzaulanıde meneiherapy ae alpha rcectes.Pualue to determino sgnféance for OS of combination and
‘monotherapy treatment comparisons was dependent on outcomes of primary endpoint and key secondary endponis. ° Safety populton.
1. Mps-cinicatias govistudy/NCTOZ919837, 2. Shore NO et al AUA 2029. Abstract LBAU2-09. 3. Freediand SJ eta M Engl J Med, 2023:380:1453-1465 as
4. Freediand S] et a. NEJM Evid, 20232. 5. Shore ND et al. ASCO GU 2024, Abstract 15.8. Shore ND et al ASCO GU 2024, Abstract 15. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Week 37
Key Eligibility Criteria Enzalutamide 160 mg oral QD +
+ Screening PSA 21 ng/mL after RP leuprolide acetate 2 5 mg IM Q12W = Suspend
and 22 ng/mL above the nadir for (n= 355 8
primary EBRT Blinded 3 ene
+ PSADT <9 mo Placebo + E nitor PSA
+ No metastases on bone scan or CT/MRI e de mentor
ad leuprolide acetate 22.5 mg IN É (reinitiate if
+ Testosterone 2150 ng/dL El nad El PSA rises)®
+ Prior hormonal therapy 29 mo prior to 3
RT (neoadjuvant/adjuvant for 536 mo Y
OR <6 mo for rising PSA) Enzalutamide 160 mg oral QD < Remain on
2
treatment
N= 1,068 Unblinded
Stratification: screening PSA (s10 ng/mL vs >10 ng/mL), PSADT (<3 mo vs >3 to <9 mo), prior hormonal therapy (yes vs no)
Primary endpoint®: MFS by BICR (enzalutamide + leuprolide acetate vs leuprolide acetate)
Key secondary endpoints®“; MFS by BICR (enzalutamide vs leuprolide acetate), time to PSA progression, time to first use of new antineoplastic
therapy, OS*
+ Other secondary endpoints: safety, PRO
+ study tenen was suspended once a week 37 PSA was <02 nom and restated when PSA vas 250 np. (tout pot RP) and 22 nio RP). IT population. Prima
(np and key secondary endpont e eneaisamide combina and enzaulanıde meneiherapy ae alpha rcectes.Pualue to determino sgnféance for OS of combination and
‘monotherapy treatment comparisons was dependent on outcomes of primary endpoint and key secondary endponis. ° Safety populton.
1. Mps-cinicatias govistudy/NCTOZ919837, 2. Shore NO et al AUA 2029. Abstract LBAU2-09. 3. Freediand SJ eta M Engl J Med, 2023:380:1453-1465 as
4. Freediand S] et a. NEJM Evid, 20232. 5. Shore ND et al. ASCO GU 2024, Abstract 15.8. Shore ND et al ASCO GU 2024, Abstract 15. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Phase 3 EMBARK: Met Primary Endpoint of MFS'2
Median follow-up, mo 60.7
Events, No. (%) 45 (13)
3y rate MMS per BICR, mo NR
100 192.9% (85% Cl ne.
Enzalutamide
combination
Key Secondary Endpoint:
Interim OS
HR = 0.59
(95% Cl, 0.38-0.90)
+ 7 P=.01428
HR = 0.42 (95% Cl, 0.31-0.61)
P<.0001"
6 12 18 24 30
ES (pre-specified efficacy
PA boundary, P < .0001)
as
Data cutott January 31, 2023. Symbol indicate censored data *HR was based on a Cox regression model wth treatment as the only covariate stated by screening PSA, PSADT,
and pror hormonal therapy a8 reparted in he WAS, relative o leuprolide acetate <1 favoring enzalutamide combination. the two-sided P value was based on
satis ogrank N
Shore ND et al AUA 2023. Abstract LBAD2-09. 2. Freedland Set al. N Engl J Med. 2023:380:1459-1465 PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Median follow-up, mo 60.7
Events, No. (%) 45 (13)
3y rate MMS per BICR, mo NR
100 192.9% (85% Cl ne.
Enzalutamide
combination
Key Secondary Endpoint:
Interim OS
HR = 0.59
(95% Cl, 0.38-0.90)
+ 7 P=.01428
HR = 0.42 (95% Cl, 0.31-0.61)
P<.0001"
6 12 18 24 30
ES (pre-specified efficacy
PA boundary, P < .0001)
as
Data cutott January 31, 2023. Symbol indicate censored data *HR was based on a Cox regression model wth treatment as the only covariate stated by screening PSA, PSADT,
and pror hormonal therapy a8 reparted in he WAS, relative o leuprolide acetate <1 favoring enzalutamide combination. the two-sided P value was based on
satis ogrank N
Shore ND et al AUA 2023. Abstract LBAD2-09. 2. Freedland Set al. N Engl J Med. 2023:380:1459-1465 PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Phase 3 EMBARK: Time to PSA Progression!?
Key Secondary Endpoint
Events, n (%) 80) 93 (28)
Madea ime FSS NR (NR) NR (NR)
progression, mo (95% Cl)
Enzalutamide combination
3
8
8
Leuprolide acetate
20 | HR = 0.07 (95% Cl, 0.03-0.14)
PSA Progression Free, %
0 6 2 1 2% 0 % a 4 OO © & 7 7% % S
— Time, mo
TREES ne rae a me mn ne
(Data euto January 31, 2023. Symbols indicate censored data * The HR was based on a Cox regression model with eatment as the only covariate stratified by
screening PSA, PSADT. and por hormonal therapy as reported in the IWS; relative to leupraide acetate <1 favoring enzalutamide combination; the tworsided P value
ls based on a statis log-rank test
4. Shore NO etal AUA 2023, Abstract LBAD2-09 2, Freecland SJ et al. N Engl J Med, 2023:309:1450-1465
PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Key Secondary Endpoint
Events, n (%) 80) 93 (28)
Madea ime FSS NR (NR) NR (NR)
progression, mo (95% Cl)
Enzalutamide combination
3
8
8
Leuprolide acetate
20 | HR = 0.07 (95% Cl, 0.03-0.14)
PSA Progression Free, %
0 6 2 1 2% 0 % a 4 OO © & 7 7% % S
— Time, mo
TREES ne rae a me mn ne
(Data euto January 31, 2023. Symbols indicate censored data * The HR was based on a Cox regression model with eatment as the only covariate stratified by
screening PSA, PSADT. and por hormonal therapy as reported in the IWS; relative to leupraide acetate <1 favoring enzalutamide combination; the tworsided P value
ls based on a statis log-rank test
4. Shore NO etal AUA 2023, Abstract LBAD2-09 2, Freecland SJ et al. N Engl J Med, 2023:309:1450-1465
PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Phase 3 EMBARK: MFS for Enzalutamide Monotherapy
Versus Leuprolide Acetate’?
Key Secondary Endpoint MEAT
Events, n (%) 63 (18) 92 (26)
MMES per BICR, mo (95% Cl) NR (NR) NR (85.1-NR)
100
so
3 Enzalutamide effect was se
2 60 | November 2023: FDA approved monotherapy tree
¢ for patients with high-risk BCR = En ee
3 « prostate cancer? Leuprolide acetate MES a
(85% Cl, 0.40-0.78)
2 P=.0006
o
0 © Ro D 0 © 42 4 6s © © 7 78 ES Key Secondary
nues Time, mo Endpoint: Interim OS
DURS none sw om me am mm & #6 0 0 HR = 0.77
a (95% Cl, 0.51-1.15)
ata tot: January 3, 2023. Symbols nia censored dt, The HR was based on a Cox regression mode wth atmen asthe any Nominal P = .1963°
covarate stated by screening PSA, PSADT, and prior hormonal therapy as reported in the IWRS; relative fo leupolide acetate <1favoring
‘enzautamide monotherapy; the two-sided Palue was based on a stated log rank es.
1 Shore ND et a. AUA 2023. Abstract LBA02-09.2. Freeland SJ etal. N Engl J Med. 2023:389:1453-145. 3. ts. fda govlrugstesouroes-nformaton-
_approved-crugs/da-approves-enzallamide-non-metastate castration sensite-prostte-cancerbicchemicalecurrence
PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
Versus Leuprolide Acetate’?
Key Secondary Endpoint MEAT
Events, n (%) 63 (18) 92 (26)
MMES per BICR, mo (95% Cl) NR (NR) NR (85.1-NR)
100
so
3 Enzalutamide effect was se
2 60 | November 2023: FDA approved monotherapy tree
¢ for patients with high-risk BCR = En ee
3 « prostate cancer? Leuprolide acetate MES a
(85% Cl, 0.40-0.78)
2 P=.0006
o
0 © Ro D 0 © 42 4 6s © © 7 78 ES Key Secondary
nues Time, mo Endpoint: Interim OS
DURS none sw om me am mm & #6 0 0 HR = 0.77
a (95% Cl, 0.51-1.15)
ata tot: January 3, 2023. Symbols nia censored dt, The HR was based on a Cox regression mode wth atmen asthe any Nominal P = .1963°
covarate stated by screening PSA, PSADT, and prior hormonal therapy as reported in the IWRS; relative fo leupolide acetate <1favoring
‘enzautamide monotherapy; the two-sided Palue was based on a stated log rank es.
1 Shore ND et a. AUA 2023. Abstract LBA02-09.2. Freeland SJ etal. N Engl J Med. 2023:389:1453-145. 3. ts. fda govlrugstesouroes-nformaton-
_approved-crugs/da-approves-enzallamide-non-metastate castration sensite-prostte-cancerbicchemicalecurrence
PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
PeerView.com/YWU827
EMBARK: Safety Profile’
Enzalutamide Combination Leuprolide Acetate | Enzalutamide Monotherapy
Event, n (%)* {n = 353) (n = 354) (n= 354)
Any AE 343(97.2) 164(46.5) 345(97.5) 151(427) 347(98.0) 177 (50.0)
Treatment-related AE 305 (86.4) 62 (17.6) 283 (79.9) 31(88) 312(881) 57 (16.1)
Serious AE 123 (34.8) 110(312) 112(31.6) 100(282) 131(370) 116 (32.8)
Treatment-related serious AE 26 (7.4) 22 (6.2) 8 (2.3) 7(20) 17 (4.8) 17 (4.8)
AE leading to dose reduction 25 (7.1) 11 (3.1) 16 (4.5) 5(1.4) 56 (15.8) 14 (4.0)
o penuanen! 73 (20.7) 31 (6.8) 36 (10.2) 1969) 6317.8) 34(26)
discontinuation
AE leading to death sam 30.8» 8 (2.3
+ Median treatment duration excluding treatment suspension was 32.4 mo (range, 0.1-83.4 mo) for enzalutamide combination,
35.4 mo (range, 0.7-85.7 mo) for leuprolide acetate, and 45.9 mo (0.4-88.9 mo) for enzalutamide monotherapy
+ The most common AE leading to study drug discontinuation was fatigue (enzalutamide combination, 3.4% [n = 12); leuprolide
acetate, 1.1% [n = 4]; enzalutamide monotherapy, 2.3% [n = 8])
Enzalutamide combination or enzalutamide monotherapy improved MFS compared with
placebo + leuprolide acetate without negatively affecting overall HRQOL
Data cutott January 31, 2023. "Percentages may not otal 100 because of rounding. Shown are AES that occured tom the time of rst dose of study treatment through
30 d ater permanent discontinuation. AES were graded according tothe NCI CTCAE vi.03, "Grade 5 AE: none were considered weatmentelated.
1. Shore ND et al AUA 2023. Abstract LBAO2-09. 2. Freedland Si eta. N Engl J Med. 2023;389:1483-1465, 3. Freeland SJ tal. NEJM Evid. 20232 i
4. Freeland SJ etl, SUO 2023. Abstract 41 PeerView.com
Copyright © 2000-2024, PeerView
EMBARK: Safety Profile’
Enzalutamide Combination Leuprolide Acetate | Enzalutamide Monotherapy
Event, n (%)* {n = 353) (n = 354) (n= 354)
Any AE 343(97.2) 164(46.5) 345(97.5) 151(427) 347(98.0) 177 (50.0)
Treatment-related AE 305 (86.4) 62 (17.6) 283 (79.9) 31(88) 312(881) 57 (16.1)
Serious AE 123 (34.8) 110(312) 112(31.6) 100(282) 131(370) 116 (32.8)
Treatment-related serious AE 26 (7.4) 22 (6.2) 8 (2.3) 7(20) 17 (4.8) 17 (4.8)
AE leading to dose reduction 25 (7.1) 11 (3.1) 16 (4.5) 5(1.4) 56 (15.8) 14 (4.0)
o penuanen! 73 (20.7) 31 (6.8) 36 (10.2) 1969) 6317.8) 34(26)
discontinuation
AE leading to death sam 30.8» 8 (2.3
+ Median treatment duration excluding treatment suspension was 32.4 mo (range, 0.1-83.4 mo) for enzalutamide combination,
35.4 mo (range, 0.7-85.7 mo) for leuprolide acetate, and 45.9 mo (0.4-88.9 mo) for enzalutamide monotherapy
+ The most common AE leading to study drug discontinuation was fatigue (enzalutamide combination, 3.4% [n = 12); leuprolide
acetate, 1.1% [n = 4]; enzalutamide monotherapy, 2.3% [n = 8])
Enzalutamide combination or enzalutamide monotherapy improved MFS compared with
placebo + leuprolide acetate without negatively affecting overall HRQOL
Data cutott January 31, 2023. "Percentages may not otal 100 because of rounding. Shown are AES that occured tom the time of rst dose of study treatment through
30 d ater permanent discontinuation. AES were graded according tothe NCI CTCAE vi.03, "Grade 5 AE: none were considered weatmentelated.
1. Shore ND et al AUA 2023. Abstract LBAO2-09. 2. Freedland Si eta. N Engl J Med. 2023;389:1483-1465, 3. Freeland SJ tal. NEJM Evid. 20232 i
4. Freeland SJ etl, SUO 2023. Abstract 41 PeerView.com
Copyright © 2000-2024, PeerView
Impact of Enzalutamide Treatment Suspension?!
EMBARK study treatment was Among those with treatment suspension,
suspended at week 37 if PSA was patients receiving enzalutamide
undetectable (<0.2 ng/mL) combination vs leuprolide alone were
also more likely to have undetectable PSA
Enzalutamide u (16.8% vs 9.6%; P = 009) and remain
monotherapy treatment-free 2 years after treatment
304 patients (86%) suspension (34.6% vs 27.1%; P = 044)
suspended treatment
Offers greater opportunity for
Leuprolide acetate (. treatment de-intensification
240 patients (67%) _N
suspended treatment
in patients with a favorable
biochemical response
1. Shore ND et al ASCO GU 2024 Abstract 15. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
EMBARK study treatment was Among those with treatment suspension,
suspended at week 37 if PSA was patients receiving enzalutamide
undetectable (<0.2 ng/mL) combination vs leuprolide alone were
also more likely to have undetectable PSA
Enzalutamide u (16.8% vs 9.6%; P = 009) and remain
monotherapy treatment-free 2 years after treatment
304 patients (86%) suspension (34.6% vs 27.1%; P = 044)
suspended treatment
Offers greater opportunity for
Leuprolide acetate (. treatment de-intensification
240 patients (67%) _N
suspended treatment
in patients with a favorable
biochemical response
1. Shore ND et al ASCO GU 2024 Abstract 15. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Phase 3 PRESTO: Androgen Blockade Intensification in
High-Risk BCR Prostate Cancer!
52-wk treatment period
Key Eligibility Criteria LHRH analog + apalutamide +
+ Prior radical prostatectomy abiraterone acetate + prednisone
+ BCR with PSA >0.5 ng/mL
+ PSA-DT <9 mo
+ No metastases on conventional imaging LHRH analog + apalutamide
+ Last dose of ADT >9 mo prior to study entry
+ Prior adjuvant/salvage RT unless not a
candidate for RT
ent per investigator discretion
N= 503 LHRH analog
Follow up for PSA pre
+ Stratification: PSADT (<3 mo vs 3-9 mo)
+ Primary endpoint: biochemical PFS (PSA >0.2 ng/mL) for each experimental arm vs control
+ Secondary endpoints: safety, patient-reported QOL, time to testosterone recovery, MFS, time to castration resistance
At first planned interim analysis, both experimental arms significantly prolonged PSA-PFS compared with control arm
+ Median, 24.9 mo for ADT + APA vs 20.3 mo for ADT; HR = 0.52 (95% Cl, 0.35-0.77); P = 00047
+ Median, 26.0 mo for ADT + APA + AAP vs 20.0 mo for ADT; HR = 0.48 (95% Cl, 0.32-0.71); P= .00008
1. Aggarwal Reta. J Cin Oncol 2024:42-1114-1123. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
High-Risk BCR Prostate Cancer!
52-wk treatment period
Key Eligibility Criteria LHRH analog + apalutamide +
+ Prior radical prostatectomy abiraterone acetate + prednisone
+ BCR with PSA >0.5 ng/mL
+ PSA-DT <9 mo
+ No metastases on conventional imaging LHRH analog + apalutamide
+ Last dose of ADT >9 mo prior to study entry
+ Prior adjuvant/salvage RT unless not a
candidate for RT
ent per investigator discretion
N= 503 LHRH analog
Follow up for PSA pre
+ Stratification: PSADT (<3 mo vs 3-9 mo)
+ Primary endpoint: biochemical PFS (PSA >0.2 ng/mL) for each experimental arm vs control
+ Secondary endpoints: safety, patient-reported QOL, time to testosterone recovery, MFS, time to castration resistance
At first planned interim analysis, both experimental arms significantly prolonged PSA-PFS compared with control arm
+ Median, 24.9 mo for ADT + APA vs 20.3 mo for ADT; HR = 0.52 (95% Cl, 0.35-0.77); P = 00047
+ Median, 26.0 mo for ADT + APA + AAP vs 20.0 mo for ADT; HR = 0.48 (95% Cl, 0.32-0.71); P= .00008
1. Aggarwal Reta. J Cin Oncol 2024:42-1114-1123. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
Treatment Can Be Intensified
Without Compromising HRQOL
EMBARK Post Hoc Analysis!
Numerical trend in HRQOL improvement after
week 37 treatment suspension was seen in all
3 arms
Post treatment suspension, all arms reached
clinically meaningful improvement in hormonal
treatment side effects at the subsequent
assessments of week 49 to week 97
Patients slowly deteriorated, with clinically
meaningful deterioration at week 205 relative
to week 37
Post hoc analysis confirmed that treatment
suspension, as expected, led to clinically
meaningful improvements in HRQOL
1. Freeland S3 etal, ASCO 2024, Abstract $005. 2. Chen R et al. ASCO 2024, Abstract $006.
PeerView.com/YWU827
PRESTO HRQOL Findings?
Intensified androgen blockade with
apalutamide vs ADT alone improved PFS-PFS
No statistically significant mean difference was
reported between intensified androgen
receptor blockade vs ADT alone in HRQOL
measures:
SAE
Time to testosterone recovery
Hormonal symptoms
Sexual dysfunction
Hot flash interference
Fatigue
PeerView.com
Copyright © 2000-2024, PeerView
Without Compromising HRQOL
EMBARK Post Hoc Analysis!
Numerical trend in HRQOL improvement after
week 37 treatment suspension was seen in all
3 arms
Post treatment suspension, all arms reached
clinically meaningful improvement in hormonal
treatment side effects at the subsequent
assessments of week 49 to week 97
Patients slowly deteriorated, with clinically
meaningful deterioration at week 205 relative
to week 37
Post hoc analysis confirmed that treatment
suspension, as expected, led to clinically
meaningful improvements in HRQOL
1. Freeland S3 etal, ASCO 2024, Abstract $005. 2. Chen R et al. ASCO 2024, Abstract $006.
PeerView.com/YWU827
PRESTO HRQOL Findings?
Intensified androgen blockade with
apalutamide vs ADT alone improved PFS-PFS
No statistically significant mean difference was
reported between intensified androgen
receptor blockade vs ADT alone in HRQOL
measures:
SAE
Time to testosterone recovery
Hormonal symptoms
Sexual dysfunction
Hot flash interference
Fatigue
PeerView.com
Copyright © 2000-2024, PeerView
Phase 3 ARASTEP: Darolutamide Plus ADT
in High-Risk BCR Prostate Cancer’?
Key Eligibility Criteria
+ High-risk BCR defined as
24-mo treatment period
No metastasis on conventional Darontarniae
imaging 600 mg PO twice daily lim RSA)
— PSADT <12 mo on progression
= PSA 20.2 ng/mL after RP followed by
ART or SRT (or RP alone in patients
unfit for ART or SRT) OR
-PSA 22 ng/mL after primary RT only
—21 PSMA PETICT positive lesions
+ 21 PSMA PETICT positive lesions
Placebo
PO twice daily + A
1:1
(N = 750)
PSMA PETICT at any time
+ Stratification factors PSADT <6 mo vs 26 to <12 mo, ITT baseline PSMA PET/CT lesions with
IGRT/surgery (yes vs no), distant metastasis (+ locoregional lesions) vs locoregional lesions only
+ Primary endpoint: rPFS by PSMA PET/CT assessed by BICR
+ Secondary endpoints: MFS by conventional imaging by BICR, time to CRPC, time to initiation of
first subsequent systemic antineoplastic therapy, time to locoregional progression by PSMA PET/CT,
time to first SSE, OS, PSA <0.2 ng/mL at 12 mo, time to deterioration in FACT-P total score, safety
1. ps ciicatias govistudy/NCTOS794908. 2. Chehrazi-Rafle A etal, ASCO GU 2024. Abstract TPS254, ee
3. ChehraziRafe A et al ASCO 2024. Abstract TPSS122. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
in High-Risk BCR Prostate Cancer’?
Key Eligibility Criteria
+ High-risk BCR defined as
24-mo treatment period
No metastasis on conventional Darontarniae
imaging 600 mg PO twice daily lim RSA)
— PSADT <12 mo on progression
= PSA 20.2 ng/mL after RP followed by
ART or SRT (or RP alone in patients
unfit for ART or SRT) OR
-PSA 22 ng/mL after primary RT only
—21 PSMA PETICT positive lesions
+ 21 PSMA PETICT positive lesions
Placebo
PO twice daily + A
1:1
(N = 750)
PSMA PETICT at any time
+ Stratification factors PSADT <6 mo vs 26 to <12 mo, ITT baseline PSMA PET/CT lesions with
IGRT/surgery (yes vs no), distant metastasis (+ locoregional lesions) vs locoregional lesions only
+ Primary endpoint: rPFS by PSMA PET/CT assessed by BICR
+ Secondary endpoints: MFS by conventional imaging by BICR, time to CRPC, time to initiation of
first subsequent systemic antineoplastic therapy, time to locoregional progression by PSMA PET/CT,
time to first SSE, OS, PSA <0.2 ng/mL at 12 mo, time to deterioration in FACT-P total score, safety
1. ps ciicatias govistudy/NCTOS794908. 2. Chehrazi-Rafle A etal, ASCO GU 2024. Abstract TPS254, ee
3. ChehraziRafe A et al ASCO 2024. Abstract TPSS122. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
ARAMIS Update: Achieving a Lower PSA With Darolutamide
Plus ADT in nmCRPC Reduces Recurrence Risk!
The ARAMIS trial showed that darolutamide increased OS vs placebo (HR = 0.69; 95% CI
0.53-0.88) and notably reduced prostate cancer-related deaths?
— PSA levels at the time of radiological progression were evaluated in patients with PSA
<0.2 ng/mL and who experienced radiological progression
Patients receiving darolutamide with PSA <0.2 ng/mL had a lower risk of radiological
progression vs those with PSA 20.2 ng/mL, with rates of 8.7% vs 33% at 24 months
At 36 months, the cumulative incidence of radiological progression remained at 8.7%
for darolutamide patients with PSA <0.2 ng/mL and increased to 50% in patients with
PSA 20.2 ng/mL
In patients with nmCRPC by conventional imaging, darolutamide increased OS vs placebo
Darolutamide + ADT resulted in deep and durable PSA response vs ADT alone
Darolutamide was associated with low rates of PSA progression + radiological progression
1. Morgans AK etal. ASCO 2024. Abstract 5022. 2. FizaziK etal N Engl J Med, 2020;383:1040-1049, PeerView.com
Copyright © 2000-2024, PeerView
Plus ADT in nmCRPC Reduces Recurrence Risk!
The ARAMIS trial showed that darolutamide increased OS vs placebo (HR = 0.69; 95% CI
0.53-0.88) and notably reduced prostate cancer-related deaths?
— PSA levels at the time of radiological progression were evaluated in patients with PSA
<0.2 ng/mL and who experienced radiological progression
Patients receiving darolutamide with PSA <0.2 ng/mL had a lower risk of radiological
progression vs those with PSA 20.2 ng/mL, with rates of 8.7% vs 33% at 24 months
At 36 months, the cumulative incidence of radiological progression remained at 8.7%
for darolutamide patients with PSA <0.2 ng/mL and increased to 50% in patients with
PSA 20.2 ng/mL
In patients with nmCRPC by conventional imaging, darolutamide increased OS vs placebo
Darolutamide + ADT resulted in deep and durable PSA response vs ADT alone
Darolutamide was associated with low rates of PSA progression + radiological progression
1. Morgans AK etal. ASCO 2024. Abstract 5022. 2. FizaziK etal N Engl J Med, 2020;383:1040-1049, PeerView.com
Copyright © 2000-2024, PeerView
Patient Advocacy Organizations Are Valuable Resources
ZERO O0 Prostate Cancer Support Grou
PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
ZERO O0 Prostate Cancer Support Grou
PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
Audience Q&A O z
Copyright © 2000-2024, PeerView
Copyright © 2000-2024, PeerView
Prostate Cancer Challenge
What was the primary endpoint of the phase 3 PEACE-1 study?
os
rPFS
rPFS and OS
MFS
PeerView.com/YWU827
What was the primary endpoint of the phase 3 PEACE-1 study?
os
rPFS
rPFS and OS
MFS
PeerView.com/YWU827
Prostate Cancer Challenge
What was the HR for OS in the initial report of the ARASENS trial?
0.98
PeerView.com/YWU827
What was the HR for OS in the initial report of the ARASENS trial?
0.98
PeerView.com/YWU827
Treatment Intensification
in mHSPC
Pedro C. Barata, MD, MSc, FACP
Miggo Family Chair in Cancer Research
Co-Leader Genitourinary (GU) Disease Team
Director of GU Medical Oncology Research Program
University Hospitals Seidman Cancer Center
Associate Professor of Medicine
Case Western Reserve University
Case Comprehensive Cancer Center
Cleveland, Ohio
Copyright © 2000-2024, PeerView
in mHSPC
Pedro C. Barata, MD, MSc, FACP
Miggo Family Chair in Cancer Research
Co-Leader Genitourinary (GU) Disease Team
Director of GU Medical Oncology Research Program
University Hospitals Seidman Cancer Center
Associate Professor of Medicine
Case Western Reserve University
Case Comprehensive Cancer Center
Cleveland, Ohio
Copyright © 2000-2024, PeerView
Presentation and Prognosis of mHSPC12
Prognosis according to volume and presentation at diagnosis
ith the poorest progn
Liver disease and <3bonelesions A Cale. x
ADO spot; Ju? see sie been pode: Metachronous/Low volume 128 (60) 7.167.106)
Metachronous/High volume 67 (75) 46 (37,67)
De novo/Low volume 96 (70) 43(40,6.5)
De novo/High volume 148 (84) 3.6 (3.1,4.7)
Pe Overall Survival
os
os
ot Metschtv.
Denovonv
02 Mera
De novomv
o
MEEZEZLELTEIT.
Time From ADT Start, mo o
1. Barata P et al, Cancer 2018:125:1777-1788.2. Francia E et al. Prostate 2018,78:880-805 PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Prognosis according to volume and presentation at diagnosis
ith the poorest progn
Liver disease and <3bonelesions A Cale. x
ADO spot; Ju? see sie been pode: Metachronous/Low volume 128 (60) 7.167.106)
Metachronous/High volume 67 (75) 46 (37,67)
De novo/Low volume 96 (70) 43(40,6.5)
De novo/High volume 148 (84) 3.6 (3.1,4.7)
Pe Overall Survival
os
os
ot Metschtv.
Denovonv
02 Mera
De novomv
o
MEEZEZLELTEIT.
Time From ADT Start, mo o
1. Barata P et al, Cancer 2018:125:1777-1788.2. Francia E et al. Prostate 2018,78:880-805 PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Impact of Phase 3 Trials in a Real-World Setting!
100
NHT
M Abiraterone
Apalutamide
I Darolutamide
49 MM Enzalutamide
Patients, %
ADT+ ADT+ NHT NHT Taxane CT TaxaneCT Other Other
Ast-gen NSAA stgen NSAA 2016-2018 2019-2020 £NHT ENHT 2016-2018 2019-2020
2016-2018 2019-2020 2016-2018 2019-2020
1. Barata Petal. Oncologist 2023:28:780-789. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
100
NHT
M Abiraterone
Apalutamide
I Darolutamide
49 MM Enzalutamide
Patients, %
ADT+ ADT+ NHT NHT Taxane CT TaxaneCT Other Other
Ast-gen NSAA stgen NSAA 2016-2018 2019-2020 £NHT ENHT 2016-2018 2019-2020
2016-2018 2019-2020 2016-2018 2019-2020
1. Barata Petal. Oncologist 2023:28:780-789. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
Unmet Needs in mHSPC13
Patients with mHSPC have poor clinical outcomes
Many patients still receive ADT monotherapy or
first-generation anti-androgen therapies
Despite level 1 evidence for improved OS with combination regimens,
adoption has been insufficient
1. MarN et al J Gin Oncol. 2021:30(supp 6}21. 2. Goebel P. ESMO 2021. Abstract 6237. 3. Swami U etal. J Cin Oncol. 202139 (suppl 16/5072. 2. .
4! George D et al J Gin Oncol. 2021:30(uppl 15-5074. 5. Swami U et al. Cancers. 2021: 134051 PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Patients with mHSPC have poor clinical outcomes
Many patients still receive ADT monotherapy or
first-generation anti-androgen therapies
Despite level 1 evidence for improved OS with combination regimens,
adoption has been insufficient
1. MarN et al J Gin Oncol. 2021:30(supp 6}21. 2. Goebel P. ESMO 2021. Abstract 6237. 3. Swami U etal. J Cin Oncol. 202139 (suppl 16/5072. 2. .
4! George D et al J Gin Oncol. 2021:30(uppl 15-5074. 5. Swami U et al. Cancers. 2021: 134051 PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Level 1 Evidence for Improved OS in mHSPC
With Treatment Intensification"?
Clinical Trial(s) Intervention Control Comments
Prostate radiation + ADT ADT =
STAMPEDE-H ae en Benefit in low-volume subgroup
GETUG-15
CHAARTED Docetaxel + ADT ADT Benefit in high-volume subgroup
STAMPEDE-C
LATITUDE : =
en Abiraterone + ADT ADT Similar benefits by risk group
ARCHES ,
Anes Enzalutamide + ADT ADT Similar benefits by risk group
TITAN Apalutamide + ADT ADT Similar benefits by risk group
ARASENS Darolutamide + ADT + docetaxel ADT + docetaxel Shar OS enamores
and de novo metastatic disease
ay Abiraterone + ADT + docetaxel ADT + docetaxel PFS benefit for all;
(+ prostate radiation) (+ prostate radiation) OS benefit in high-volume
1. Parker CC et al Lancet. 2018:3922353-2388, 2. Armstrong A eal. J Cn Oncol. 2022:40:1618-1622. 3. Davi ID el. Engl J Med. 2019:391:121-131.
4: James N etal. Lancet 2016;387:1163-1177. 5, Sweeney CJ et al N Engl J Med. 2015:373797-748, 6. ChiKN et al. N Engl J Med, 2019;381:13-24,
7. FizaziK et al. NEngl J Med, 2017:377'352-360, 8. James NO et a. N Engl J Med. 2017.377:338:351. 9. Smith MR e al. N Engl J Med, 2022:386:1132-1142. en
10.FizaziK e al, Lancet 2022.309:1605-1707. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
With Treatment Intensification"?
Clinical Trial(s) Intervention Control Comments
Prostate radiation + ADT ADT =
STAMPEDE-H ae en Benefit in low-volume subgroup
GETUG-15
CHAARTED Docetaxel + ADT ADT Benefit in high-volume subgroup
STAMPEDE-C
LATITUDE : =
en Abiraterone + ADT ADT Similar benefits by risk group
ARCHES ,
Anes Enzalutamide + ADT ADT Similar benefits by risk group
TITAN Apalutamide + ADT ADT Similar benefits by risk group
ARASENS Darolutamide + ADT + docetaxel ADT + docetaxel Shar OS enamores
and de novo metastatic disease
ay Abiraterone + ADT + docetaxel ADT + docetaxel PFS benefit for all;
(+ prostate radiation) (+ prostate radiation) OS benefit in high-volume
1. Parker CC et al Lancet. 2018:3922353-2388, 2. Armstrong A eal. J Cn Oncol. 2022:40:1618-1622. 3. Davi ID el. Engl J Med. 2019:391:121-131.
4: James N etal. Lancet 2016;387:1163-1177. 5, Sweeney CJ et al N Engl J Med. 2015:373797-748, 6. ChiKN et al. N Engl J Med, 2019;381:13-24,
7. FizaziK et al. NEngl J Med, 2017:377'352-360, 8. James NO et a. N Engl J Med. 2017.377:338:351. 9. Smith MR e al. N Engl J Med, 2022:386:1132-1142. en
10.FizaziK e al, Lancet 2022.309:1605-1707. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
OS Benefit Confirmed With AR-Targeting Agents
OS, %
83338
(apalutamide) pp 4 apt
Median OS: NR
Placebo + ADT
Median OS: 52.2 mo
0 6 12 18
PeerView.com/YWU827
Patients Alive, %
LATITUDE?
(abiraterone)
12 18 24 30 36 42 48 54 60 66
ime, mo
1.CHKN et al J Clin Oncol. 2021:30:2204-2303. 2. Armstrong Ad etal. J Cin Oncol. 2022:41:1616-1822. 3. FizaziK etal Lancet Oncol. 2019;20:686-700.
ARCHES?
(enzalutamide) enzalutamide + ADT
Median OS: NR
Placebo + ADT
Median OS; NR
Placebo + ADT
a a 36 4 48 54 ©
Time, mo
PeerView.com
Copyright © 2000-2024, PeerView
OS, %
83338
(apalutamide) pp 4 apt
Median OS: NR
Placebo + ADT
Median OS: 52.2 mo
0 6 12 18
PeerView.com/YWU827
Patients Alive, %
LATITUDE?
(abiraterone)
12 18 24 30 36 42 48 54 60 66
ime, mo
1.CHKN et al J Clin Oncol. 2021:30:2204-2303. 2. Armstrong Ad etal. J Cin Oncol. 2022:41:1616-1822. 3. FizaziK etal Lancet Oncol. 2019;20:686-700.
ARCHES?
(enzalutamide) enzalutamide + ADT
Median OS: NR
Placebo + ADT
Median OS; NR
Placebo + ADT
a a 36 4 48 54 ©
Time, mo
PeerView.com
Copyright © 2000-2024, PeerView
Lessons Learned From Doublet Trials
Combining ADT with ARPI improves all clinically meaningful
efficacy endpoints (eg, rPFS, OS)
In addition to efficacy, QOL is also maintained—or even
improved—with these combination regimens
What if an ARPI and docetaxel
are used together in a triplet combination?
PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Combining ADT with ARPI improves all clinically meaningful
efficacy endpoints (eg, rPFS, OS)
In addition to efficacy, QOL is also maintained—or even
improved—with these combination regimens
What if an ARPI and docetaxel
are used together in a triplet combination?
PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Phase 3 PEACE-1: Abiraterone Plus Prednisone
Key Eligibility Criteria
De novo mHSPC
Distant metastatic disease”
On-study requirement
of continuous ADT
ADT <3 mo permitted
Stratification
ECOG PS (0 vs 1-2)
Site of metastases
(LN vs bone vs viscera)
Castration type (orchiectomy vs
GnRH agonist vs GnRH
antagonist)
Docetaxel (yes vs no)
N = 1,173
in De Novo mHSPC'.
SOC + abiraterone‘
SOC + RT
SOC + RT +
abirateroned
Primary endpoints:
rPFS and OS
‘Intemational, mulicener, prospective, randomized tal conducted in seven counties by the Prostate Cancer Consortium in Europe (PEACE); started accruing in 2013,
Based on the presence of lesion on bone scan andlor CT scan. «SOC was iniialy ADT alone; rom 1012015 to 2017, SOC arm was ADT + docetaxel per investigators
<iscretion: tom 2017, accrual restricted to ADT + docetaxel as SOC. "Abraterone 1,000 mglday, 4 tablets of 250 mplday PO along with prednisone 5 mg BID.
1. ps eniealviats gowstudyNCTO1957436.
PeerView.com/YWU827
PeerView.com
Copyright © 2000-2024, PeerView
Key Eligibility Criteria
De novo mHSPC
Distant metastatic disease”
On-study requirement
of continuous ADT
ADT <3 mo permitted
Stratification
ECOG PS (0 vs 1-2)
Site of metastases
(LN vs bone vs viscera)
Castration type (orchiectomy vs
GnRH agonist vs GnRH
antagonist)
Docetaxel (yes vs no)
N = 1,173
in De Novo mHSPC'.
SOC + abiraterone‘
SOC + RT
SOC + RT +
abirateroned
Primary endpoints:
rPFS and OS
‘Intemational, mulicener, prospective, randomized tal conducted in seven counties by the Prostate Cancer Consortium in Europe (PEACE); started accruing in 2013,
Based on the presence of lesion on bone scan andlor CT scan. «SOC was iniialy ADT alone; rom 1012015 to 2017, SOC arm was ADT + docetaxel per investigators
<iscretion: tom 2017, accrual restricted to ADT + docetaxel as SOC. "Abraterone 1,000 mglday, 4 tablets of 250 mplday PO along with prednisone 5 mg BID.
1. ps eniealviats gowstudyNCTO1957436.
PeerView.com/YWU827
PeerView.com
Copyright © 2000-2024, PeerView
PEACE-1: Improved rPFS With Abiraterone
in the ADT + Docetaxel (+ RT) Population’
Abirat
(n = 355) (= 355)
Median, y(lOR) 4:46(19NR) 203 (1.08-NR)
3e 100 Events, No. 139 211
@ go HR (99.9% Cl); P 0.50 (0.34-0.71); <.0001
¢ RE ETE.
a
$
2 60
a
8 40 SOC + abiraterone
ES soc
5 20
[4
o
0 1 2 3 4 5
No, at Risk may
soc 355 274 137 61 16 o
SOC + abiraterone 355 303 200 105 35 o
Adding abiraterone to ADT + docetaxel significantly improved rPFS
1. FizaziK etal. Lancet, 2022.399:1695-1707, PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
in the ADT + Docetaxel (+ RT) Population’
Abirat
(n = 355) (= 355)
Median, y(lOR) 4:46(19NR) 203 (1.08-NR)
3e 100 Events, No. 139 211
@ go HR (99.9% Cl); P 0.50 (0.34-0.71); <.0001
¢ RE ETE.
a
$
2 60
a
8 40 SOC + abiraterone
ES soc
5 20
[4
o
0 1 2 3 4 5
No, at Risk may
soc 355 274 137 61 16 o
SOC + abiraterone 355 303 200 105 35 o
Adding abiraterone to ADT + docetaxel significantly improved rPFS
1. FizaziK etal. Lancet, 2022.399:1695-1707, PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
PEACE-1: Improved OS in De Novo mHSPC!
Overall Population ADT + Docetaxel Population
SOC + abiraterone groups SOC + abiraterone groups
SOC without abiraterone groups SOC without abiraterone groups
Median OS: 5.7 y vs 4.7 y
HR = 0.82 (95.1% Cl, 0.69-0.98); P = .030
5 6
Median OS: NR vs 4.4 y
HR = 0.75 (95.1% Cl, 0.59-0.95); P = .017
2 3 4 5
2 3 4 1
Time Since Randomization, y Time Since Randomization, y
1. FizaziK et al. Lancet. 2022:399:1895-1707.
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Overall Population ADT + Docetaxel Population
SOC + abiraterone groups SOC + abiraterone groups
SOC without abiraterone groups SOC without abiraterone groups
Median OS: 5.7 y vs 4.7 y
HR = 0.82 (95.1% Cl, 0.69-0.98); P = .030
5 6
Median OS: NR vs 4.4 y
HR = 0.75 (95.1% Cl, 0.59-0.95); P = .017
2 3 4 5
2 3 4 1
Time Since Randomization, y Time Since Randomization, y
1. FizaziK et al. Lancet. 2022:399:1895-1707.
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Phase 3 ARASENS: Darolutamide Plus ADT
Plus Docetaxel in mHSPC'
International trial conducted at >300 sites in 23 countries
ECOG PS 0 or 1
+ Extent of disease
ALP level
Planned N = 1
+ Primary endpoint: OS
Key Eligibility Criteria
+ Newly diagnosed metastatic disease
Stratification
,300
ADT + docetaxel x 6 cycles
+ darolutamide
600 mg by mouth twice daily
ADT + docetaxel x 6 cycles
+ placebo
* Key secondary endpoints: time to mCRPC, time to initiation of subsequent anticancer
therapy, time to SSE-free survival, time to first SSE, time to pain progression
1. htpsetnicatals govstudyiNCTO2799602.
PeerView.com/YWU827
PeerView.com
Copyright © 2000-2024, PeerView
Plus Docetaxel in mHSPC'
International trial conducted at >300 sites in 23 countries
ECOG PS 0 or 1
+ Extent of disease
ALP level
Planned N = 1
+ Primary endpoint: OS
Key Eligibility Criteria
+ Newly diagnosed metastatic disease
Stratification
,300
ADT + docetaxel x 6 cycles
+ darolutamide
600 mg by mouth twice daily
ADT + docetaxel x 6 cycles
+ placebo
* Key secondary endpoints: time to mCRPC, time to initiation of subsequent anticancer
therapy, time to SSE-free survival, time to first SSE, time to pain progression
1. htpsetnicatals govstudyiNCTO2799602.
PeerView.com/YWU827
PeerView.com
Copyright © 2000-2024, PeerView
ARASENS: Improved OS With Darolutamide
Plus ADT Plus Docetaxel’
August 2023: FDA approved for
patients with mHSPC?
Darolutamide
Patients Alive, %
Median survival, mo (95% Cl)
Darolutamide: NE vs placebo: 48.9 (44.4-NE)
HR = 0.68 (95% Cl, 0.57-0.80)
P<.001
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60
Time, mo
No. at Risk
Darolutamide 651 645 637 627 608 593 570 548 525 509 486 468 452 436 402 267 139 56 9 0
o
Placebo
654 646 630 607 580 565 536 510 488 470 441 424 402 383 340 218 107 37 6 1 0
4. Smith MR et al. N Engl J Med. 2022:388:1132-1142
2 HS wr fda govlrugsiresoutcesnlormabon-approved:drugs/ida-approves-darlutamide-tablets-metastachormone-sensiive-prostate-cancer PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Plus ADT Plus Docetaxel’
August 2023: FDA approved for
patients with mHSPC?
Darolutamide
Patients Alive, %
Median survival, mo (95% Cl)
Darolutamide: NE vs placebo: 48.9 (44.4-NE)
HR = 0.68 (95% Cl, 0.57-0.80)
P<.001
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60
Time, mo
No. at Risk
Darolutamide 651 645 637 627 608 593 570 548 525 509 486 468 452 436 402 267 139 56 9 0
o
Placebo
654 646 630 607 580 565 536 510 488 470 441 424 402 383 340 218 107 37 6 1 0
4. Smith MR et al. N Engl J Med. 2022:388:1132-1142
2 HS wr fda govlrugsiresoutcesnlormabon-approved:drugs/ida-approves-darlutamide-tablets-metastachormone-sensiive-prostate-cancer PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
OS by Metastatic Stage at Initial Diagnosis!
De Novo Metastatic
ease Recurrent Metastatic Disease
100
Darolutamide
Darolutamide
Patients Alive, %
HR for death = 0.71 (95% Cl, 0.59-0.85)
Patients Alive, %
°c888888388
HR for death = 0.61 (95% Cl, 0.35-1.05)
0 3 6 9 1215 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57
Time, mo Time, mo
Post-Hoc Analysis?
+ Post-progression survival was similar independent of subsequent anticancer therapy with an ARPI or chemotherapy
+ Greater OS benefit and delayed disease progression to mCRPC were observed with early treatment intensification
ith the darolutamide combination
4. Smith MR et al N Engl J Med. 2022:386:1132-1142. 2. Grimm N-O eta, ASCO 2024. Abstract 5083. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
De Novo Metastatic
ease Recurrent Metastatic Disease
100
Darolutamide
Darolutamide
Patients Alive, %
HR for death = 0.71 (95% Cl, 0.59-0.85)
Patients Alive, %
°c888888388
HR for death = 0.61 (95% Cl, 0.35-1.05)
0 3 6 9 1215 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57
Time, mo Time, mo
Post-Hoc Analysis?
+ Post-progression survival was similar independent of subsequent anticancer therapy with an ARPI or chemotherapy
+ Greater OS benefit and delayed disease progression to mCRPC were observed with early treatment intensification
ith the darolutamide combination
4. Smith MR et al N Engl J Med. 2022:386:1132-1142. 2. Grimm N-O eta, ASCO 2024. Abstract 5083. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
ARASENS: Volume and Risk Subgroups’
High-Volume mHSPC. Low-Volume mHSPC
Darolutemide + ADT + docetaxel
Median, mo: NR (95% Cl, NR-NR)
Darolutamido + ADT + docetaxel
Median, mo: NR (95% Cl, 5038) * 60
Risk of death reduced
co
Foo
jo jo by ~30% across
ee En lume and risk groups
Hig 5% Placebo + ADT + docetaxel volume and risk groups
ae a: Median, mo: NR (95% Cl, NR-NR) mOS not reached in
20 EN the darolutamide
22 Median, mor A ci 397460) 2% group, regardiess of
¿a ¿a volume or risk
2 > HR = 0.69 (95% Cl, 0.57-0.82) é HR = 0.68 (95% Cl, 0.41-1.13) Favorable safety profile
ERRE ETE TREPA ERRE RPP EFFES as confirmed in all
Time, mo Time, mo :
» 2 volume and risk
= High-Risk mHsPe m SE <uncroun populations,
Darolutamide + ADT + docetaxel as Se
xe ni Tee 0 Median, mo: NR (85% Cl, NRNR) consistent with the
is ge overall ARASENS
ge eo population
3 Placebo + ADT + docetaxel thccanalys
2] rncebo + ADT + docetaxst ge Median, mo: NR (95% CI NRAR) e
E ©] edian, mo: 432 (05% Ch 400489) ¿o demonstrated deep
q qa and durable PSA
¿o
responses
3: uerariosiciasioso 3] mmnscrnesciociosn i
o p
ODES MIM MM ODW Hawa OSE MMT DIATE
Time, mo Time, mo
1. Hussain Metal ASCO GU 2023, Abstract 15.2. Saad Fetal. J Url 2023:209:0580. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
High-Volume mHSPC. Low-Volume mHSPC
Darolutemide + ADT + docetaxel
Median, mo: NR (95% Cl, NR-NR)
Darolutamido + ADT + docetaxel
Median, mo: NR (95% Cl, 5038) * 60
Risk of death reduced
co
Foo
jo jo by ~30% across
ee En lume and risk groups
Hig 5% Placebo + ADT + docetaxel volume and risk groups
ae a: Median, mo: NR (95% Cl, NR-NR) mOS not reached in
20 EN the darolutamide
22 Median, mor A ci 397460) 2% group, regardiess of
¿a ¿a volume or risk
2 > HR = 0.69 (95% Cl, 0.57-0.82) é HR = 0.68 (95% Cl, 0.41-1.13) Favorable safety profile
ERRE ETE TREPA ERRE RPP EFFES as confirmed in all
Time, mo Time, mo :
» 2 volume and risk
= High-Risk mHsPe m SE <uncroun populations,
Darolutamide + ADT + docetaxel as Se
xe ni Tee 0 Median, mo: NR (85% Cl, NRNR) consistent with the
is ge overall ARASENS
ge eo population
3 Placebo + ADT + docetaxel thccanalys
2] rncebo + ADT + docetaxst ge Median, mo: NR (95% CI NRAR) e
E ©] edian, mo: 432 (05% Ch 400489) ¿o demonstrated deep
q qa and durable PSA
¿o
responses
3: uerariosiciasioso 3] mmnscrnesciociosn i
o p
ODES MIM MM ODW Hawa OSE MMT DIATE
Time, mo Time, mo
1. Hussain Metal ASCO GU 2023, Abstract 15.2. Saad Fetal. J Url 2023:209:0580. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
Darolutamide Plus ADT in mHSPC
Phase 2 ARASEC: Darolutamide Plus ADT in mHSPC*
Key Eligibility Criteria Darolutamide + ADT ne + Primary endpoint: PFS
+ Confirmed adenocarcinoma of ARASEC open-label arm + Secondary endpoints:
the prostate Patients matched 1:10n | Os Prs, time to
Maton deseas on baseline characteristics, ere
tic disease Hans CRPC, rate of
conventional imaging ADT alo He nes undetectable PSA
+ ECOG PS 0-2 Historical control arm from (eg, age, response (<0.2 ng/mL)
ECOG PS, CHAARTED-
defined extent of disease,
prior therapy)
+ ADT started <120 days before
initiation of darolutamide
at 6 mo, safety
+ Primary endpoint: rPFS
Darolutamide + Secondary endpoints: OS, time
600 mg BID PO + ADT to CRPC, time to initiation of
subsequent anticancer therapy,
time to PSA progression, rate of
undetectable PSA response (<0.2
ng/mL) at 6 mo, time to pain
progression, safety
1. ps www: cnica gov/tucyNCTOS059296. 2. Mtps/ieSnicalvalsgowstudy/NCTO4726169. PeerView.com
Key Eligibility Criteria
+ Confirmed metastatic disease by
central review
Stratification
+ Presence or absence of visceral
metastases by central review Placebo + ADT
+ Prior vs no prior local therapy
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
Phase 2 ARASEC: Darolutamide Plus ADT in mHSPC*
Key Eligibility Criteria Darolutamide + ADT ne + Primary endpoint: PFS
+ Confirmed adenocarcinoma of ARASEC open-label arm + Secondary endpoints:
the prostate Patients matched 1:10n | Os Prs, time to
Maton deseas on baseline characteristics, ere
tic disease Hans CRPC, rate of
conventional imaging ADT alo He nes undetectable PSA
+ ECOG PS 0-2 Historical control arm from (eg, age, response (<0.2 ng/mL)
ECOG PS, CHAARTED-
defined extent of disease,
prior therapy)
+ ADT started <120 days before
initiation of darolutamide
at 6 mo, safety
+ Primary endpoint: rPFS
Darolutamide + Secondary endpoints: OS, time
600 mg BID PO + ADT to CRPC, time to initiation of
subsequent anticancer therapy,
time to PSA progression, rate of
undetectable PSA response (<0.2
ng/mL) at 6 mo, time to pain
progression, safety
1. ps www: cnica gov/tucyNCTOS059296. 2. Mtps/ieSnicalvalsgowstudy/NCTO4726169. PeerView.com
Key Eligibility Criteria
+ Confirmed metastatic disease by
central review
Stratification
+ Presence or absence of visceral
metastases by central review Placebo + ADT
+ Prior vs no prior local therapy
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
Safety Considerations for Doublet or Triplet Therapy
blet Therapy Triplet Therapy
oO Monitoring with abiraterone (HTN,
edema, LFTs, hypokalemia)
: Chemotherapy toxicity
[Pill burden O (neutropenia, neuropathy, fatigue)
[1 Infusional treatment
[] Exacerbation of ADT AEs [I] Time
oO All considerations associated with
oO CV, cognitive, bone health doublet therapy
PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
blet Therapy Triplet Therapy
oO Monitoring with abiraterone (HTN,
edema, LFTs, hypokalemia)
: Chemotherapy toxicity
[Pill burden O (neutropenia, neuropathy, fatigue)
[1 Infusional treatment
[] Exacerbation of ADT AEs [I] Time
oO All considerations associated with
oO CV, cognitive, bone health doublet therapy
PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Audience Q&A O z
Copyright © 2000-2024, PeerView
Copyright © 2000-2024, PeerView
Prostate Cancer Challenge
Which of the following is NOT an FDA-approved PARP inhibitor + ARSI
combination therapy for patients with mCRPC?
Olaparib + abiraterone
Niraparib + abiraterone
Talazoparib + abiraterone
Talazoparib + enzalutamide
PeerView.com/YWU827
Which of the following is NOT an FDA-approved PARP inhibitor + ARSI
combination therapy for patients with mCRPC?
Olaparib + abiraterone
Niraparib + abiraterone
Talazoparib + abiraterone
Talazoparib + enzalutamide
PeerView.com/YWU827
Prostate Cancer Challenge 63
Name this PARP inhibitor:
Olaparib
Niraparib
Talazoparib
Rucaparib
Name this PARP inhibitor:
Olaparib
Niraparib
Talazoparib
Rucaparib
Expanding Therapeutic Reach
With Combination Approaches
Hormonal Therapy Plus PARP Inhibitors
Kim N. Chi, MD, FRCPC
BC Cancer
Vancouver Prostate Centre
University of British Columbia [Pl
Vancouver, British Columbia, Canada ”
Copyright © 2000-2024, PeerView
With Combination Approaches
Hormonal Therapy Plus PARP Inhibitors
Kim N. Chi, MD, FRCPC
BC Cancer
Vancouver Prostate Centre
University of British Columbia [Pl
Vancouver, British Columbia, Canada ”
Copyright © 2000-2024, PeerView
PARP Inhibitors for the
Treatment of Prostate Cancer!
PARP Inhibitor Monotherapy PARP Inhibitor Combination Therapy
a Olaparib + abiraterone
Olaparib + PROpel
+ PROfound
+ FDA approved for HRRanutatea moRPC « FDA approved for BRCA-mutated mCRPC
pP! Niraparib + abiraterone as a fixed-dose
combination tablet?
Rucaparib + MAGNITUDE
+ TRITON2 + FDA approved for BRCA-mutated mCRPC
+ FDA approved for BRCA-mutated Talazoparib + enzalutamide
mERPC® + TALAPRO-2
+ FDA approved for HRR-mutated mCRPC
* Accelerated approval continued approval may be contingent upon conmatoy phase 3 ia. irec-dose combination tablet: niraparb 200 mg and abaterone
‘acetate 1,000 mg taken orally once daly in combination wth prednisone 10 mg dai. —
Ft ra cimealtals go PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Treatment of Prostate Cancer!
PARP Inhibitor Monotherapy PARP Inhibitor Combination Therapy
a Olaparib + abiraterone
Olaparib + PROpel
+ PROfound
+ FDA approved for HRRanutatea moRPC « FDA approved for BRCA-mutated mCRPC
pP! Niraparib + abiraterone as a fixed-dose
combination tablet?
Rucaparib + MAGNITUDE
+ TRITON2 + FDA approved for BRCA-mutated mCRPC
+ FDA approved for BRCA-mutated Talazoparib + enzalutamide
mERPC® + TALAPRO-2
+ FDA approved for HRR-mutated mCRPC
* Accelerated approval continued approval may be contingent upon conmatoy phase 3 ia. irec-dose combination tablet: niraparb 200 mg and abaterone
‘acetate 1,000 mg taken orally once daly in combination wth prednisone 10 mg dai. —
Ft ra cimealtals go PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Biologic Rationale for Combination
PARP and AR Inhibition'*
+ AR signaling promotes DNA
damage repair
+ PARP1 regulates AR-mediated — NAcamae
transcriptional activation
+ AR inhibition upregulates PARP-mediated
repair pathways with synthetic lethality
between ADT and PARP inhibition
1. Goodwin J et al. Cancer Discov. 2013:3:1254. 2. Pokinghom WR etal. Cancer Discov. 2013:3:1245, rn
3. Asim Me al. Nat Commun, 2017.8:374. 4. Schiewer MJ el al Cancer Discov. 201221134, PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
PARP and AR Inhibition'*
+ AR signaling promotes DNA
damage repair
+ PARP1 regulates AR-mediated — NAcamae
transcriptional activation
+ AR inhibition upregulates PARP-mediated
repair pathways with synthetic lethality
between ADT and PARP inhibition
1. Goodwin J et al. Cancer Discov. 2013:3:1254. 2. Pokinghom WR etal. Cancer Discov. 2013:3:1245, rn
3. Asim Me al. Nat Commun, 2017.8:374. 4. Schiewer MJ el al Cancer Discov. 201221134, PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
PARPi + ARPI Phase 3 Trials: Similar But Different
MAGNITUDE’ TALAPRO-2%4
ARPI Abiraterone Abiraterone Enzalutamide
PARPI Niraparib 200 mg PO OD Olaparib 300 mg BID Talazoparib
Primary endpoint TPFS by BICR 1PFS by investigator 1PFS by BICR
Design Analysis Separate cohorts Retrospective Stratified and separate cohorts
Biomarker testing Prospective Retrospective Prospective
ATM, BRCA1, BRCA2, ATM, BRCAT, BRCA2, BARDI, — BRCA1, BRCA2, PALB2, ATM,
BP) car Conia crise raca, ERP COK CHEKT, CHEK Arm exo FANOA RADSTC
Intervention
HDAC2, PALB2 RDC Rabu panei, NBN.MLHI, MRETTA CDKI2
‘All comers: 805
u ee he HRR cohort: 399
BRCA: 225 85 eee.
2 All comers: 110
Population | HRR/non-BRCA 198 141 HRR cohort: 241
MOTHER 233 570 All comers: 642
Liver metastases 73% 41% NA
Pain Mean BPLSF: 1.19 BPLSF <3: 75% NA
‘J Cin Oncol 2023:41:3339-3351. 2. Saad F et al Lancet Oncol 2023,24:1094-1108. 3 Agarwal N et al Lancet. 2023,402.201.300.
"Nature Med. 2024.30 257-264 PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
MAGNITUDE’ TALAPRO-2%4
ARPI Abiraterone Abiraterone Enzalutamide
PARPI Niraparib 200 mg PO OD Olaparib 300 mg BID Talazoparib
Primary endpoint TPFS by BICR 1PFS by investigator 1PFS by BICR
Design Analysis Separate cohorts Retrospective Stratified and separate cohorts
Biomarker testing Prospective Retrospective Prospective
ATM, BRCA1, BRCA2, ATM, BRCAT, BRCA2, BARDI, — BRCA1, BRCA2, PALB2, ATM,
BP) car Conia crise raca, ERP COK CHEKT, CHEK Arm exo FANOA RADSTC
Intervention
HDAC2, PALB2 RDC Rabu panei, NBN.MLHI, MRETTA CDKI2
‘All comers: 805
u ee he HRR cohort: 399
BRCA: 225 85 eee.
2 All comers: 110
Population | HRR/non-BRCA 198 141 HRR cohort: 241
MOTHER 233 570 All comers: 642
Liver metastases 73% 41% NA
Pain Mean BPLSF: 1.19 BPLSF <3: 75% NA
‘J Cin Oncol 2023:41:3339-3351. 2. Saad F et al Lancet Oncol 2023,24:1094-1108. 3 Agarwal N et al Lancet. 2023,402.201.300.
"Nature Med. 2024.30 257-264 PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
MAGNITUDE: Niraparib Plus Abiraterone in mCRPC!
Key Eligibility Criteria
aL mCRPC
— <4 mo prior abiraterone
Prescreening for Allocation to Cohort
Biomarker Status
Niraparib +
HRR BM+ abiraterone
allowed for mCRPC. Pan
+ ECOG PSOort ATM Placebo +
+ BPI-SF worst pain score <3 BRCA1 abiraterone
BRCA2 Prospectively selecto
Stratification BRIP1 ‘cohorts designed to
+ Prior taxane-based chemo for CDK12 les
MBSPC CHEK2 Niraparib +
+ Prior ARi for nmCRPC FANCA Cohort 2 abiraterone
HDAC2 HRR BM-
+ Prior abiraterone for 1L mCRPC
+ HRR BM+ cohort only
= BRCA1/2 vs other HRR gene
alterations (HRR BM+ cohort)
PALB2
(n=233) R Placebo +
abiraterone
+ Primary endpoint: rPFS by central review; met at IA1
+ Secondary endpoints: OS, time to symptomatic progression, time to cytotoxicity chemotherapy, safety
1. tps inicatiais gow/studyiNCTO374B641, PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
Key Eligibility Criteria
aL mCRPC
— <4 mo prior abiraterone
Prescreening for Allocation to Cohort
Biomarker Status
Niraparib +
HRR BM+ abiraterone
allowed for mCRPC. Pan
+ ECOG PSOort ATM Placebo +
+ BPI-SF worst pain score <3 BRCA1 abiraterone
BRCA2 Prospectively selecto
Stratification BRIP1 ‘cohorts designed to
+ Prior taxane-based chemo for CDK12 les
MBSPC CHEK2 Niraparib +
+ Prior ARi for nmCRPC FANCA Cohort 2 abiraterone
HDAC2 HRR BM-
+ Prior abiraterone for 1L mCRPC
+ HRR BM+ cohort only
= BRCA1/2 vs other HRR gene
alterations (HRR BM+ cohort)
PALB2
(n=233) R Placebo +
abiraterone
+ Primary endpoint: rPFS by central review; met at IA1
+ Secondary endpoints: OS, time to symptomatic progression, time to cytotoxicity chemotherapy, safety
1. tps inicatiais gow/studyiNCTO374B641, PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
MAGNITUDE: Niraparib Plus Abiraterone in mCRPC12
August 2023: FDA approved for
patients with BRCAm mCRPC34 as
a fixed-dose combination
(once-daily dual-action tablet)?
142: rPFS by Central Review in the BRCA Subgroup
80
+ 1A1: improved rPFS with NIRA +
AAP compared with placebo + AAP
= NIRA + AAP: median 19.5 mo
in patients with BRCA+ mCRPC
16.6 vs 10.9 mo (HR = 0.53; 95% Cl,
0.36-0.79; P= .001)
142: 45% reduction in the risk of
progression or death and extension
of the median rPFS to >1.5 y
0 3 6 9 2 15 18 21 24 27 30 33 36 compared with placebo + AAP
Time, mo
40
20
Patients Without Event, %
HR = 0.56 (95% Cl, 0.39-0.78) Placebo + AAP: median 10.9 mo
P=.
Fiec-dose combination tablet irapan 200 mg and abrterone acetate 1,000 mg taken ral once daly in combination vih prednisone 10 mg day.
1. Oh KN et al J Gin Oncol 202341:3339-3351. 2. Ch KN etal ESMO 2023. LBABS. 3 ps www fa govlrugs/exources-eformation-approved-drugs!
(Sa-approves-nrapanb-and-abraterone-aceate-pls-prednisone-brca-mulatedmelastal-casrabon 4. Akeega (nrapanb and abraterone acetate) n
Presenbing Information. hips ww accessdat fda. govidrugsatida_docsiabel2023/216793s0000 pal, PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
August 2023: FDA approved for
patients with BRCAm mCRPC34 as
a fixed-dose combination
(once-daily dual-action tablet)?
142: rPFS by Central Review in the BRCA Subgroup
80
+ 1A1: improved rPFS with NIRA +
AAP compared with placebo + AAP
= NIRA + AAP: median 19.5 mo
in patients with BRCA+ mCRPC
16.6 vs 10.9 mo (HR = 0.53; 95% Cl,
0.36-0.79; P= .001)
142: 45% reduction in the risk of
progression or death and extension
of the median rPFS to >1.5 y
0 3 6 9 2 15 18 21 24 27 30 33 36 compared with placebo + AAP
Time, mo
40
20
Patients Without Event, %
HR = 0.56 (95% Cl, 0.39-0.78) Placebo + AAP: median 10.9 mo
P=.
Fiec-dose combination tablet irapan 200 mg and abrterone acetate 1,000 mg taken ral once daly in combination vih prednisone 10 mg day.
1. Oh KN et al J Gin Oncol 202341:3339-3351. 2. Ch KN etal ESMO 2023. LBABS. 3 ps www fa govlrugs/exources-eformation-approved-drugs!
(Sa-approves-nrapanb-and-abraterone-aceate-pls-prednisone-brca-mulatedmelastal-casrabon 4. Akeega (nrapanb and abraterone acetate) n
Presenbing Information. hips ww accessdat fda. govidrugsatida_docsiabel2023/216793s0000 pal, PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
MAGNITUDE: 3-Year Update and Final Analysis!
OS at Final Analysis (Unadjusted)
NIRA + AAP
mos:
HR = 0.788 (95% Cl, 0.554-1.120)
Nominal P = 1828 PBO + AAP
MVA: HR = 0.663 (95% Cl, 0.464-0.947)
Nominal P= .0237
8 6 8 8 8
Patients Without Event, %
o
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48
Time, mo
With 11.1 mo of additional follow-up from 1A2
and 19.2 mo from IA1, OS favored NIRA + AAP
in patients with BRCA+ mCRPC
1.CHKN et al ESMO 2023. LEABS,
PeerView.com/YWU827
Patients Without Event, %.
Patients Without Event, %
3
Time to Symptomatic Progression
NIRA + AAP
PBO + AAP
HR = 0.562 (95% Cl, 0.371-0.849)
Nominal P = .0056
CTS eROUANT OHM MAGS
Time, mo
Time to Cytotoxic Chemotherapy
NIRA + AAP
HR = 0.598 (95% Cl, 0.387-0.924)
Nominal P=.0192
ERELTITELZTTIITZ)
Time, mo .
PeerView.com
Copyright © 2000-2024, PeerView
OS at Final Analysis (Unadjusted)
NIRA + AAP
mos:
HR = 0.788 (95% Cl, 0.554-1.120)
Nominal P = 1828 PBO + AAP
MVA: HR = 0.663 (95% Cl, 0.464-0.947)
Nominal P= .0237
8 6 8 8 8
Patients Without Event, %
o
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48
Time, mo
With 11.1 mo of additional follow-up from 1A2
and 19.2 mo from IA1, OS favored NIRA + AAP
in patients with BRCA+ mCRPC
1.CHKN et al ESMO 2023. LEABS,
PeerView.com/YWU827
Patients Without Event, %.
Patients Without Event, %
3
Time to Symptomatic Progression
NIRA + AAP
PBO + AAP
HR = 0.562 (95% Cl, 0.371-0.849)
Nominal P = .0056
CTS eROUANT OHM MAGS
Time, mo
Time to Cytotoxic Chemotherapy
NIRA + AAP
HR = 0.598 (95% Cl, 0.387-0.924)
Nominal P=.0192
ERELTITELZTTIITZ)
Time, mo .
PeerView.com
Copyright © 2000-2024, PeerView
PROpel: Olaparib Plus Abiraterone in mCRPC*
Stratification
Olaparib 300 mg BID +
1L mCRPC o een abiraterone 1,000 mg QD?
Docetaxel allowed at ee (n= 399)
mHSPC stage
(bone only
No prior abiraterone ee eed
Other NHAs allowed vs other)
if stopped 212 mo iss Placebo +
+ Prior taxane RER
prior to enrollment at mHSPC abiraterone 1,000 mg QD
Ongoing ADT (yes vs no) (n= 397
ECOG 0-1
+ Primary endpoint: rPFS
* Secondary endpoint: OS (alpha control)
* First patient randomized: November 2018; last patent randomized: March 2020; DCO!! July 30, 2021, or intern analysis of rPFS and OS. Mute ts
procedures are used in is study: one-sided alpha 010.025 fly located to rPFS. I rPFS results statistical signifeant, OS tobe tested in a hierarchical fashion
‘wth alpha passed onto OS. In combinaton wth prednisone or predníslone 5 mg BI. be
1: Aps.chicahnals govistucy/NGTOS732820, PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Stratification
Olaparib 300 mg BID +
1L mCRPC o een abiraterone 1,000 mg QD?
Docetaxel allowed at ee (n= 399)
mHSPC stage
(bone only
No prior abiraterone ee eed
Other NHAs allowed vs other)
if stopped 212 mo iss Placebo +
+ Prior taxane RER
prior to enrollment at mHSPC abiraterone 1,000 mg QD
Ongoing ADT (yes vs no) (n= 397
ECOG 0-1
+ Primary endpoint: rPFS
* Secondary endpoint: OS (alpha control)
* First patient randomized: November 2018; last patent randomized: March 2020; DCO!! July 30, 2021, or intern analysis of rPFS and OS. Mute ts
procedures are used in is study: one-sided alpha 010.025 fly located to rPFS. I rPFS results statistical signifeant, OS tobe tested in a hierarchical fashion
‘wth alpha passed onto OS. In combinaton wth prednisone or predníslone 5 mg BI. be
1: Aps.chicahnals govistucy/NGTOS732820, PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
PROpel: PFS and OS in the ITT Population’?
úlapario + Abiraerone _ Placebo + Abiraerone Olapari + Abiraerene — Placebo + Abiraterone
PFS ( 19) (m=397) (n= 397)
Medan FS, mo En 108 Medan OS, mo #21 ur
Evens, No.) 168421) 2291609) Events, No. (6) mon 205 (616)
HR 05% CH; 209 054081) <0001 HR (5% CHR 031 (097-100) 0544"
10 t2mora
os an 24morate
os ñ 514%
Eros
07
os
os
0
02
or
Olaparib +
a Aram
Probability of PFS
Probability of 0S
Placebo + abiraterone A
CITI ss ERELLITIIETTTTTEIEIIZZZZ)
Time From Randomization, mo Time, mo.
* 2sided boundary or significance: 0377: 47.9% matt}. a
1. Clarke NW et al. MEJM Evi. 2022:19). 2. Saad F et a. Lancet Oncol 2023:24:1094-1108. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
úlapario + Abiraerone _ Placebo + Abiraerone Olapari + Abiraerene — Placebo + Abiraterone
PFS ( 19) (m=397) (n= 397)
Medan FS, mo En 108 Medan OS, mo #21 ur
Evens, No.) 168421) 2291609) Events, No. (6) mon 205 (616)
HR 05% CH; 209 054081) <0001 HR (5% CHR 031 (097-100) 0544"
10 t2mora
os an 24morate
os ñ 514%
Eros
07
os
os
0
02
or
Olaparib +
a Aram
Probability of PFS
Probability of 0S
Placebo + abiraterone A
CITI ss ERELLITIIETTTTTEIEIIZZZZ)
Time From Randomization, mo Time, mo.
* 2sided boundary or significance: 0377: 47.9% matt}. a
1. Clarke NW et al. MEJM Evi. 2022:19). 2. Saad F et a. Lancet Oncol 2023:24:1094-1108. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
PROpel: PFS and OS in HRRm Population (Including BRCA)!
PFS os
10
os en
0. ”
so
¿a bad, 10 úAbiraterono + olapaib
Bos aa zo
2 ge EventsPatens, Median 08, mo
Bos 8 « E
e, 30 TT
2 EventsPatients, 20 À Abiaterone + placebo 69/115(60) 28.5 (262-044) ap ts
Es Medan, mo
ra 0 [messer 005045099)
E
02 . EERNEXEELLELTLEETEEIZITZ)
ax | Abate pucto Tans ers) 198 Abraterone + placebo
ma alo Time From Random Assignment, mo
o
OT ESTE OTE OWI SIT TDN RUMI ON
‘Time From Random Assignment, mo.
HR for disease progression or death.» HR for death a
1. Clarke NW etal NEUM Evi, 2022.10) PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
PFS os
10
os en
0. ”
so
¿a bad, 10 úAbiraterono + olapaib
Bos aa zo
2 ge EventsPatens, Median 08, mo
Bos 8 « E
e, 30 TT
2 EventsPatients, 20 À Abiaterone + placebo 69/115(60) 28.5 (262-044) ap ts
Es Medan, mo
ra 0 [messer 005045099)
E
02 . EERNEXEELLELTLEETEEIZITZ)
ax | Abate pucto Tans ers) 198 Abraterone + placebo
ma alo Time From Random Assignment, mo
o
OT ESTE OTE OWI SIT TDN RUMI ON
‘Time From Random Assignment, mo.
HR for disease progression or death.» HR for death a
1. Clarke NW etal NEUM Evi, 2022.10) PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
PROpel: PFS and OS in BRCA-Mutated Population Only!
May 2023: FDA approved for
BRCAm mCRPC
rPFS os
Ernst, Mein 9, mo vensPatets, Median 08, mo
Tora Te ae = ay — 0
non spaces GETS) BAGS) mc poco DNS) DM
Et 301200) Mose) Sa Grease)
10
Abiraterone + olaparib
on Placebo + abiraterone
o o
902468101214 em mann m OIEA ITZA OO 202222020 30 32 A 30 30 40 aU
Time, mo Time Since Randomization, mo
1. Saad F et al. Ann Oncol, 2022:34suppl 7)+616-2082. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
May 2023: FDA approved for
BRCAm mCRPC
rPFS os
Ernst, Mein 9, mo vensPatets, Median 08, mo
Tora Te ae = ay — 0
non spaces GETS) BAGS) mc poco DNS) DM
Et 301200) Mose) Sa Grease)
10
Abiraterone + olaparib
on Placebo + abiraterone
o o
902468101214 em mann m OIEA ITZA OO 202222020 30 32 A 30 30 40 aU
Time, mo Time Since Randomization, mo
1. Saad F et al. Ann Oncol, 2022:34suppl 7)+616-2082. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
TALAPRO-2: Talazoparib Plus Enzalutamide in mCRPC!
Key Eligibility Criteria
+ Patients with mCRPC
(adenocarcinoma of the
prostate)
+ No small cell/signet cell
Talazoparib
enzalutamide 160 mg/d
Stratification
+ Stratified by prior
novel hormonal tx or
To safety
follow-up
taxane for HSPC
= Mild oro symptom Gare) ‘erm orcas
+ PD at study entry 2 DDR ateration states every 8-12 wk
: (deficient vs
a Fe AUS nondeficient/unknown) Placebo +
enzalutamide 160 mí
N= 805
+ Primary endpoints: rPFS per RECIST v1.1 for soft-tissue disease and per PCWG3 for bone disease in
DDR-unselected and DDR-mutant populations
+ Key secondary endpoints: OS, response, PSA, PFS2, TTNT, PK, HRQOL, safety
1. Mis clica govstudyINCTO3305197 PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
Key Eligibility Criteria
+ Patients with mCRPC
(adenocarcinoma of the
prostate)
+ No small cell/signet cell
Talazoparib
enzalutamide 160 mg/d
Stratification
+ Stratified by prior
novel hormonal tx or
To safety
follow-up
taxane for HSPC
= Mild oro symptom Gare) ‘erm orcas
+ PD at study entry 2 DDR ateration states every 8-12 wk
: (deficient vs
a Fe AUS nondeficient/unknown) Placebo +
enzalutamide 160 mí
N= 805
+ Primary endpoints: rPFS per RECIST v1.1 for soft-tissue disease and per PCWG3 for bone disease in
DDR-unselected and DDR-mutant populations
+ Key secondary endpoints: OS, response, PSA, PFS2, TTNT, PK, HRQOL, safety
1. Mis clica govstudyINCTO3305197 PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
TALAPRO-2: PFS in HRR-Deficient mCRPC*
June 2023: FDA approved for patients
with HRR-mutated mCRP!
10
Enzalutamide Placebo + Enzalutamide
200)
Median PFS, mo
(5% CN NR (21.9-NR) 138 (110167)
Events, n 66 104
un 08
2
a
o 06
2 Talazoparib +
3 04 enzalutamide
3
2
Q 0.2 4 Stratified:
Placebo +
HR for disease progression or death = 0.45 (95% Cl, 0.33-0.61) de tn
P<.0001
o
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42
Time, mo
No, at Risk
Talazoparb + enzalvtamide 200 191 180 168 163 131 107 86 82 60 49 45 m 2% 21 19 9 4
Placebo +enzalutamide 108 171 149 131 128 96 67 St 47 39 29 25 21 11 7 7 4 0
1.FizaziK et al. ASCO 2023, Abstract 004. 2. AgarwalN e al. Lancet 2023:402291-303. 3. FizaziK e al Nat Mod 2024:30257-284. ñ
4: its ew 8a gOVdrugS drug approvls-aná databases ida-approves-talazopar-enzalutamide-hr ene mulated metastate castration resistant prostate PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
June 2023: FDA approved for patients
with HRR-mutated mCRP!
10
Enzalutamide Placebo + Enzalutamide
200)
Median PFS, mo
(5% CN NR (21.9-NR) 138 (110167)
Events, n 66 104
un 08
2
a
o 06
2 Talazoparib +
3 04 enzalutamide
3
2
Q 0.2 4 Stratified:
Placebo +
HR for disease progression or death = 0.45 (95% Cl, 0.33-0.61) de tn
P<.0001
o
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42
Time, mo
No, at Risk
Talazoparb + enzalvtamide 200 191 180 168 163 131 107 86 82 60 49 45 m 2% 21 19 9 4
Placebo +enzalutamide 108 171 149 131 128 96 67 St 47 39 29 25 21 11 7 7 4 0
1.FizaziK et al. ASCO 2023, Abstract 004. 2. AgarwalN e al. Lancet 2023:402291-303. 3. FizaziK e al Nat Mod 2024:30257-284. ñ
4: its ew 8a gOVdrugS drug approvls-aná databases ida-approves-talazopar-enzalutamide-hr ene mulated metastate castration resistant prostate PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
TALAPRO-2: OS in HRR-Deficient mCRPC13
Talazoparib + Enzalutamide Placebo + Enzalutamide
(n = 200) ( )
‘Median OS, mo
(xen NR (36.4-NR) 337 (27.6-NR)
10 Events, n 43 53
a 08
©
Ss
2 06 Talazoparib +
4 enzalutamide
3 04
3 Placebo +
© 02] States enzalutamide
:2 | HR for OS = 0.69 (95% CI, 0.46-1.03)
P=07
o
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42
Time, mo
No. at Risk
Talazoparb + enzaltamido 200 199 197 163 187 172 152 130 118 103 90 79 59 43 31 27 1 9 5 1 0 0
Placebo + enzahtamide 199 198 190 184 176 159 140 11 99 83 74 60 M 26 27 23 1 5 1 0 0 0
*.FizaziK et al, ASCO 2023. Abstract 004. 2. Agarwal Net al. Lancet. 2023:402291-303. 3. FzaziK e al Nat Med. 2024:30257-264. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Talazoparib + Enzalutamide Placebo + Enzalutamide
(n = 200) ( )
‘Median OS, mo
(xen NR (36.4-NR) 337 (27.6-NR)
10 Events, n 43 53
a 08
©
Ss
2 06 Talazoparib +
4 enzalutamide
3 04
3 Placebo +
© 02] States enzalutamide
:2 | HR for OS = 0.69 (95% CI, 0.46-1.03)
P=07
o
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42
Time, mo
No. at Risk
Talazoparb + enzaltamido 200 199 197 163 187 172 152 130 118 103 90 79 59 43 31 27 1 9 5 1 0 0
Placebo + enzahtamide 199 198 190 184 176 159 140 11 99 83 74 60 M 26 27 23 1 5 1 0 0 0
*.FizaziK et al, ASCO 2023. Abstract 004. 2. Agarwal Net al. Lancet. 2023:402291-303. 3. FzaziK e al Nat Med. 2024:30257-264. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Unequivocal Benefit for BRCA1/2 Mutations
MAGNITUDE PROpel TALAPRO-2
(N = 225)12 (N = 85) (N = 158)
Median, mo 19.5 vs 10.9
NR vs 8.4 NR vs 11.0
HR (95% Cl) 0.55 (0.39-0.78) 0.29 (0.14-0.56) 0.20 (0.11-0.36)
Median, mo 30.4 vs 28.6 NR vs 23.0 NIA
HR (95% Cl) 0.663 (0.464-0.947)° 0.29 (0.14-0.56) 0.61 (0.31-1.23)
Subsequent PARP = m
inhibitor in placebo arm 34% 1% (n = 5) 3% (n= 11)
2 MVA adusted.*Al-comers popa
1. GNiKN et al Ann Oncol, 2023:34:772.782. 2. Ch KN et al. ESMO 2023. Abstract LBABS2 a
3 Saad Feta. Lancet Oncol 2023:24 1094-1108. 4. Fza Ket al. Nature Med. 2024;30:257-264, PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
MAGNITUDE PROpel TALAPRO-2
(N = 225)12 (N = 85) (N = 158)
Median, mo 19.5 vs 10.9
NR vs 8.4 NR vs 11.0
HR (95% Cl) 0.55 (0.39-0.78) 0.29 (0.14-0.56) 0.20 (0.11-0.36)
Median, mo 30.4 vs 28.6 NR vs 23.0 NIA
HR (95% Cl) 0.663 (0.464-0.947)° 0.29 (0.14-0.56) 0.61 (0.31-1.23)
Subsequent PARP = m
inhibitor in placebo arm 34% 1% (n = 5) 3% (n= 11)
2 MVA adusted.*Al-comers popa
1. GNiKN et al Ann Oncol, 2023:34:772.782. 2. Ch KN et al. ESMO 2023. Abstract LBABS2 a
3 Saad Feta. Lancet Oncol 2023:24 1094-1108. 4. Fza Ket al. Nature Med. 2024;30:257-264, PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
Equivocal Benefit for Non-HRR Mutations
MAGNITUDE PROpel TALAPRO-2
(N = 233)! (N = 552)2° (N = 636)45
Median, mo 12.0 vs NE 24.1 vs 19.0 NR vs 22.5
h 1.09 0.76 0.69
9
METIO) (0.75-1.57) (0.60-0.97) (0.54-0.89)
Median, mo N/A 42.1 vs 38.9 N/A
0.89
(0.70-1.14)
HR (95% Cl) N/A N/A
1. GniKN et al. J Gin Oncol 202341:3339-3361. 2 Clarke NW et al N Engl J Med Evid, 2022.19) 3. Saad F et al. Lancet Oncol. 2023:24:1094-1108 —
4. Agarwal N ei a. Lance! 2023:402:291-300. 5. FzazK el al. Nature Med, 2024;20:257-264, PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
MAGNITUDE PROpel TALAPRO-2
(N = 233)! (N = 552)2° (N = 636)45
Median, mo 12.0 vs NE 24.1 vs 19.0 NR vs 22.5
h 1.09 0.76 0.69
9
METIO) (0.75-1.57) (0.60-0.97) (0.54-0.89)
Median, mo N/A 42.1 vs 38.9 N/A
0.89
(0.70-1.14)
HR (95% Cl) N/A N/A
1. GniKN et al. J Gin Oncol 202341:3339-3361. 2 Clarke NW et al N Engl J Med Evid, 2022.19) 3. Saad F et al. Lancet Oncol. 2023:24:1094-1108 —
4. Agarwal N ei a. Lance! 2023:402:291-300. 5. FzazK el al. Nature Med, 2024;20:257-264, PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
MAGNITUDE Results for HRR-Mutated, Non-BRCA:
Benefit Somewhere in Between!
Single-Gene IRA+ Placebo — IPFS,HR TCC,HR TSP,HR OS,HR | TPSAProgr ORR (Risk Ratio)
Alteration AAP +AAPn (95 HR NIRA vs PEO, nN (%)
053 058 068 026 046 165 (1.02-2.71),
BRCA1/2 19 12 03679) (039,101) (042111) (SH) © (030069) 2086 (62) vs 1548 (31)
059 068 0.90 043 085 T5 (036600).
HRR-Fancont #7 M (023149 (017274) (024-337) (012180) (027-159) 346 (60) vs 246 (33)
023 114 098 05 0.13-2.00)
ae A * om 3 NE woman NE 0147.00) 412 (60) vs 11 (100)
107 051 123 0.66 NE;
a ® 6 presas (0055.16) man) NE 013347) 0.1 (0)vs 0720)
BE A N 050 029 041 027 050 208197;
(01522) (002619) (003662) (005166) (016220) 278 (67) vs 13 (33)
084 072 058 023 045 54 (0964325),
rer 27) 2 (2458) (1926) (01720) (1138) (017140) 57 (71) vs 19 (19)
0.66 036 054 044 037 NE;
u 38, 20 (025176) (007-188) (0.14225) (012171) (014099) 577 (71) v8 0880)
on on 044 NE;
HDAC2 2 3 (0.06-8.02) we (0.04-11.79) _ (0.04-5:13) pe 00 (0) vs 1/3 (33)
q = = 1m 025 073 107 073 311283)
(063-199) (008080) (026-200) (044265) (03-136) 14/17 (62) ve 9/11 (27)
ae a Fr 132 13 105 161 Des 225 (0.5479;
(043-392) (027570) (02839) (049539) (024180) 3/4 (75) vs 2 (33)
1. Sandhu S etal, ASCO 2022. Abstract 5020 PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
Benefit Somewhere in Between!
Single-Gene IRA+ Placebo — IPFS,HR TCC,HR TSP,HR OS,HR | TPSAProgr ORR (Risk Ratio)
Alteration AAP +AAPn (95 HR NIRA vs PEO, nN (%)
053 058 068 026 046 165 (1.02-2.71),
BRCA1/2 19 12 03679) (039,101) (042111) (SH) © (030069) 2086 (62) vs 1548 (31)
059 068 0.90 043 085 T5 (036600).
HRR-Fancont #7 M (023149 (017274) (024-337) (012180) (027-159) 346 (60) vs 246 (33)
023 114 098 05 0.13-2.00)
ae A * om 3 NE woman NE 0147.00) 412 (60) vs 11 (100)
107 051 123 0.66 NE;
a ® 6 presas (0055.16) man) NE 013347) 0.1 (0)vs 0720)
BE A N 050 029 041 027 050 208197;
(01522) (002619) (003662) (005166) (016220) 278 (67) vs 13 (33)
084 072 058 023 045 54 (0964325),
rer 27) 2 (2458) (1926) (01720) (1138) (017140) 57 (71) vs 19 (19)
0.66 036 054 044 037 NE;
u 38, 20 (025176) (007-188) (0.14225) (012171) (014099) 577 (71) v8 0880)
on on 044 NE;
HDAC2 2 3 (0.06-8.02) we (0.04-11.79) _ (0.04-5:13) pe 00 (0) vs 1/3 (33)
q = = 1m 025 073 107 073 311283)
(063-199) (008080) (026-200) (044265) (03-136) 14/17 (62) ve 9/11 (27)
ae a Fr 132 13 105 161 Des 225 (0.5479;
(043-392) (027570) (02839) (049539) (024180) 3/4 (75) vs 2 (33)
1. Sandhu S etal, ASCO 2022. Abstract 5020 PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
TALAPRO-2 rPFS Results for HRR-Mutated, Non-BRCA:
Benefit Somewhere in Between!
AN HRR defiient
‘Only BRCAY
‘ny BRCAZ
‘On PALB2
‘ny coK12
‘Only ATM
ny CHEK2
BRCA cluster
PALB2 cluster
COK2 cluster
ATM cluster
104197
so
40160
as
1830
m2
va
Saas
se
23138
9
NR
200
NR
NR
NR
21
NR
NR
219
279
HR (95% CI) Two-Sided P
044 (032-060)
047 (002-451)
0.19 0.10038)
056 (0.12251)
0.49 0231.02)
0.76 (030-494)
NR 0.90 (0342.30)
no 020011030)
83 046 (012-487)
138 038 016076)
a7 0.90 (0392.08)
(Omer gene cluster 1942 1240 21 NR He 151073315) 28
rPFS
HRRm, non-BRCA1/2:
.68 (95% Cl, 0.46-1.02); P
1. FzaziK etal. Nature Med. 2024;30:287-264
PeerView.com/YWU827
001 00 100 100
AAA
Favors talazopar + enzalutamide Favors placebo + enzautamide
ES
HRRm non-BRCAT/BRCA2:
HR = 0.66 (95% Cl, 0.40-1.10); P=.11
PeerView.com
Copyright © 2000-2024, PeerView
Benefit Somewhere in Between!
AN HRR defiient
‘Only BRCAY
‘ny BRCAZ
‘On PALB2
‘ny coK12
‘Only ATM
ny CHEK2
BRCA cluster
PALB2 cluster
COK2 cluster
ATM cluster
104197
so
40160
as
1830
m2
va
Saas
se
23138
9
NR
200
NR
NR
NR
21
NR
NR
219
279
HR (95% CI) Two-Sided P
044 (032-060)
047 (002-451)
0.19 0.10038)
056 (0.12251)
0.49 0231.02)
0.76 (030-494)
NR 0.90 (0342.30)
no 020011030)
83 046 (012-487)
138 038 016076)
a7 0.90 (0392.08)
(Omer gene cluster 1942 1240 21 NR He 151073315) 28
rPFS
HRRm, non-BRCA1/2:
.68 (95% Cl, 0.46-1.02); P
1. FzaziK etal. Nature Med. 2024;30:287-264
PeerView.com/YWU827
001 00 100 100
AAA
Favors talazopar + enzalutamide Favors placebo + enzautamide
ES
HRRm non-BRCAT/BRCA2:
HR = 0.66 (95% Cl, 0.40-1.10); P=.11
PeerView.com
Copyright © 2000-2024, PeerView
Adverse Events With PARPi Plus ARPI: Similar But Different
MAGNITUDE HHRm Cohort PROpel All Comers. TALAPRO-2 HHRm Cohort
(n=212)* (N = 398)? (n= 198)?
AllGrades,% Grade 3-4,% AllGrades,% Grade 3-4,% AllGrades,% Grade 3-4, %
Anemia
Fatigue
Nausea 30
ITP
Neutropenia
10
Pulmonary à
embolism
Transfusion
AML/MDS
1.ChIKN et al. Ann Oncol. 2023:34:772-782. 2. Saad F e al Lancet Oncol 2023:24:1094-1108. 3. FzaziK et al. Nature Med. 2024;30:287-264, PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
MAGNITUDE HHRm Cohort PROpel All Comers. TALAPRO-2 HHRm Cohort
(n=212)* (N = 398)? (n= 198)?
AllGrades,% Grade 3-4,% AllGrades,% Grade 3-4,% AllGrades,% Grade 3-4, %
Anemia
Fatigue
Nausea 30
ITP
Neutropenia
10
Pulmonary à
embolism
Transfusion
AML/MDS
1.ChIKN et al. Ann Oncol. 2023:34:772-782. 2. Saad F e al Lancet Oncol 2023:24:1094-1108. 3. FzaziK et al. Nature Med. 2024;30:287-264, PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Expanding Reach of Combination Approaches
Earlier in Disease
Phase 3 AMPLITUDE: Niraparib + AAP in mHSPC*
Niraparib 200 mg and abiraterone acetate 1,000 mg (in + Primary Rs
Key Eligibility Criteria dual-action formulation) + prednisone 5 mg dail investigator-assessed
ren din von “0
and deleterious germline or somatic HRR
gene alteration® + Secondary
+ ADT started 214 d prior to randomization and endpoints: OS,
planned to continue through treatment phase ie rone acetate 1,000 mg + prednisone 5 mg daily symptomatic PFS,
N=788 i time to subsequent
therapy
Phase 3 TALAPRO-3: Talazoparib + Enzalutami
oy Ely Criteria Talazopar 05 m
“ame PO: + Primary endpoint:
‘rzatanie radiologic PFS
+ Secondary endpoints:
OS, objective response
and DOR in soft-tissue
disease, time to PFS
response, time to PSA
progression
Patents with qualifying HRR gene ateratons identified by localcommercial testing may be eligible. °High-olume disease is defined asthe presence of visceral
‘metastases or 24 bone lesions with 21 beyond the vertebra bodes. ”
Tips cinicaiais govIstudyNCTOM497844. 2 ps lcinicairiais gov'studyINCTO4821622 PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
Earlier in Disease
Phase 3 AMPLITUDE: Niraparib + AAP in mHSPC*
Niraparib 200 mg and abiraterone acetate 1,000 mg (in + Primary Rs
Key Eligibility Criteria dual-action formulation) + prednisone 5 mg dail investigator-assessed
ren din von “0
and deleterious germline or somatic HRR
gene alteration® + Secondary
+ ADT started 214 d prior to randomization and endpoints: OS,
planned to continue through treatment phase ie rone acetate 1,000 mg + prednisone 5 mg daily symptomatic PFS,
N=788 i time to subsequent
therapy
Phase 3 TALAPRO-3: Talazoparib + Enzalutami
oy Ely Criteria Talazopar 05 m
“ame PO: + Primary endpoint:
‘rzatanie radiologic PFS
+ Secondary endpoints:
OS, objective response
and DOR in soft-tissue
disease, time to PFS
response, time to PSA
progression
Patents with qualifying HRR gene ateratons identified by localcommercial testing may be eligible. °High-olume disease is defined asthe presence of visceral
‘metastases or 24 bone lesions with 21 beyond the vertebra bodes. ”
Tips cinicaiais govIstudyNCTOM497844. 2 ps lcinicairiais gov'studyINCTO4821622 PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
Optimizing Genetic Testing Through
Team-Based Collaboration!
Germline Genetic Testing
Recommended in patients with a personal history of prostate cancer in the following scenarios
High-risk, very high-risk, regional, or metastatic prostate cancer
Ashkenazi Jewish ancestry
Family history of high-risk germline mutations (eg, BRCA1/2, Lynch mutation)
A positive family history of cancer
Somatic Tumor Testing
+ Recommend evaluating tumor for alterations in HRR genes? in patients with metastatic prostate cancer
- Consider in patients with regional prostate cancer
+ Recommend testing for MSI-H or dMMR in mCRPC
— Consider in regional or castration-naive metastatic prostate cancer
+ Consider TMB testing in patients with mCRPC
atients with metastatic prostate cancer qualify for
he testing is positive, genetic counseling is recommended
* BRCAI, BRCA2, ATM, PALB2, FANCA, RADSID. CHEKZ, and COK12 =
1.NCCN Cinical Practice Guideines in Oncology. Prostate Cancer. Version 4.2028, htps:iwww.ncenoroprotessionalsiphyscian_os/pdprostat pt. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
Team-Based Collaboration!
Germline Genetic Testing
Recommended in patients with a personal history of prostate cancer in the following scenarios
High-risk, very high-risk, regional, or metastatic prostate cancer
Ashkenazi Jewish ancestry
Family history of high-risk germline mutations (eg, BRCA1/2, Lynch mutation)
A positive family history of cancer
Somatic Tumor Testing
+ Recommend evaluating tumor for alterations in HRR genes? in patients with metastatic prostate cancer
- Consider in patients with regional prostate cancer
+ Recommend testing for MSI-H or dMMR in mCRPC
— Consider in regional or castration-naive metastatic prostate cancer
+ Consider TMB testing in patients with mCRPC
atients with metastatic prostate cancer qualify for
he testing is positive, genetic counseling is recommended
* BRCAI, BRCA2, ATM, PALB2, FANCA, RADSID. CHEKZ, and COK12 =
1.NCCN Cinical Practice Guideines in Oncology. Prostate Cancer. Version 4.2028, htps:iwww.ncenoroprotessionalsiphyscian_os/pdprostat pt. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
Take-Home Points
+ Empiric and biologic rationale for the combination of PARPi and ARPI
+ Greatest benefit in BRCA1/2-mutated population with poor prognosis
— Niraparib + abiraterone, olaparib + abiraterone, and talazoparib +
enzalutamide are FDA approved for this indication
+ Lesser benefit in HRRm/non-BRCA-mutated population, but extent is dependent
on mutation type
— Talazoparib + enzalutamide is FDA approved for this indication
+ Equivocal clinical benefit in the HRR-negative population
+ Combination therapy has additional short- and long-term toxicities
(as expected from PARPi) that are manageable
+ Need to test to identify these patients
PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
+ Empiric and biologic rationale for the combination of PARPi and ARPI
+ Greatest benefit in BRCA1/2-mutated population with poor prognosis
— Niraparib + abiraterone, olaparib + abiraterone, and talazoparib +
enzalutamide are FDA approved for this indication
+ Lesser benefit in HRRm/non-BRCA-mutated population, but extent is dependent
on mutation type
— Talazoparib + enzalutamide is FDA approved for this indication
+ Equivocal clinical benefit in the HRR-negative population
+ Combination therapy has additional short- and long-term toxicities
(as expected from PARPi) that are manageable
+ Need to test to identify these patients
PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Audience Q&A O z
Copyright © 2000-2024, PeerView
Copyright © 2000-2024, PeerView
Prostate Cancer Challenge
What is the half-life of 177lutetium?
2.2 days
6.7 days
11.5 days
23.9 days
PeerView.com/YWU827
What is the half-life of 177lutetium?
2.2 days
6.7 days
11.5 days
23.9 days
PeerView.com/YWU827
Prostate Cancer Challenge
Among the following side effects, which one is not usually observed
with radium-223?
1. Dry mouth
2. Diarrhea
3. Thrombocytopenia
4. Anemia
PeerView.com/YWU827
Among the following side effects, which one is not usually observed
with radium-223?
1. Dry mouth
2. Diarrhea
3. Thrombocytopenia
4. Anemia
PeerView.com/YWU827
Impact of Radioligand Therapy
Karim Fizazi, MD, PhD
Professor of Medicine
GETUG President
Department of Cancer Medicine
Institut Gustave Roussy
University of Paris Saclay E
Villejuif, France
2000-2024, PeerView
Karim Fizazi, MD, PhD
Professor of Medicine
GETUG President
Department of Cancer Medicine
Institut Gustave Roussy
University of Paris Saclay E
Villejuif, France
2000-2024, PeerView
Treatment With Radium-223 Improves OS in mCRPC'2
OS, Previous Docetaxel Use OS, No Previous Docetaxel Use
Radlum-223 Placebo
(n= 352) (n= 178) Radium-223 Placebo
Median mo 144 113 (n= 262) (n= 133)
© BR 125185 100-129 Median mo 16.1 15
HR = 0.70 (95% cl, 0.56-088) ‘SKC! 139-178 95141
i ‘ 4 HR = 0.69 (95% CI, 0.52-0.92)
q P= 002 P=01
z
Em Radium-223
3
Radium-223
4 5 2 U D À 2% 2 % 40 0 4 8 2 % m
Time, mo Time, mo
2013: Radium-223 was FDA approved for
mCRPC based on the phase 3 ALSYMPCA trial
1. Hoskin Petal. Lancet Oncol. 2014:15:1397-1408.
2: Xofo (radium Ra 223 chloride) Preserbing Information. tps www accessdata da govdrugsatisa_docs/abel/2013/20307 ML at PeerView.com
PeerView.com/YWU827
Copyright © 2000-2024, PeerView
OS, Previous Docetaxel Use OS, No Previous Docetaxel Use
Radlum-223 Placebo
(n= 352) (n= 178) Radium-223 Placebo
Median mo 144 113 (n= 262) (n= 133)
© BR 125185 100-129 Median mo 16.1 15
HR = 0.70 (95% cl, 0.56-088) ‘SKC! 139-178 95141
i ‘ 4 HR = 0.69 (95% CI, 0.52-0.92)
q P= 002 P=01
z
Em Radium-223
3
Radium-223
4 5 2 U D À 2% 2 % 40 0 4 8 2 % m
Time, mo Time, mo
2013: Radium-223 was FDA approved for
mCRPC based on the phase 3 ALSYMPCA trial
1. Hoskin Petal. Lancet Oncol. 2014:15:1397-1408.
2: Xofo (radium Ra 223 chloride) Preserbing Information. tps www accessdata da govdrugsatisa_docs/abel/2013/20307 ML at PeerView.com
PeerView.com/YWU827
Copyright © 2000-2024, PeerView
REASSURE: Treatment With Radium-223 Following
External Beam Radiation Therapy?
os + In this real-world study, enzalutamide + radium-223 was
not associated with new safety signals and did not
appear to increase fracture risk
Median OS was numerically longer in the combined vs
10
os
the layered group or all-patient group
Phase 3 trial (PEACE-III) ongoing, assessing the
combination of enzalutamide with radium-223
08 JR + Elayered
o4
R+E combined
02
Survival Probability
All patients
STA
Time, mo
Median OS from All patients R+E combined R+E layered
first dose of 15.6 months 22.2 months 16.5 months
radium-223 (95% Cl, 14.6-16.5) (95% Cl, 13.7-26.8) (95% CI, 13.9-19.5)
1. Higano CS etal ECinicaMedcne, 2023:60:101903, 2. TombalB et al. ESMO 2023. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
External Beam Radiation Therapy?
os + In this real-world study, enzalutamide + radium-223 was
not associated with new safety signals and did not
appear to increase fracture risk
Median OS was numerically longer in the combined vs
10
os
the layered group or all-patient group
Phase 3 trial (PEACE-III) ongoing, assessing the
combination of enzalutamide with radium-223
08 JR + Elayered
o4
R+E combined
02
Survival Probability
All patients
STA
Time, mo
Median OS from All patients R+E combined R+E layered
first dose of 15.6 months 22.2 months 16.5 months
radium-223 (95% Cl, 14.6-16.5) (95% Cl, 13.7-26.8) (95% CI, 13.9-19.5)
1. Higano CS etal ECinicaMedcne, 2023:60:101903, 2. TombalB et al. ESMO 2023. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
PEACE-IIl: Combining Radium-223 With Enzalutamide‘2
Key Eligibility Criteria®
+ Bone-predominant mCRPC
A don) Stratification Enzalutamide 160 mg once daily
. pellets or mildly coy E radium-223 55 kBq/kg IV
symptomatic aseline pain Be
i uo u (ri as on every 4 wk for 6 cycles
+ No prior treatment with CYP17 0-1 vs 2-3)
inhibitors, enzalutamide, Prior docetaxel
radium-223 other (yes vs no)
radionucleotides, hemibody Use of bone Enzalutamide 160 mg on
radiotherapy health agents®
+ No known brain or visceral
metastases
+ Primary endpoint: rPFS
+ Secondary endpoint: OS, DSS, SSE, time to initiation of next systemic antineoplastic therapy,
PFS2, BPI, EQ-5D-5L
* Bone heath agents (denosumab or brphosphonates) only permites in patients receiving them at bassline, ination during study prohibited to prevent confounding eects -
1. hpsiesniealialsgowstudyNCTO2194842.2. Gilessen S et a, ASCO 2021. Abstract 5002. ¡com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Key Eligibility Criteria®
+ Bone-predominant mCRPC
A don) Stratification Enzalutamide 160 mg once daily
. pellets or mildly coy E radium-223 55 kBq/kg IV
symptomatic aseline pain Be
i uo u (ri as on every 4 wk for 6 cycles
+ No prior treatment with CYP17 0-1 vs 2-3)
inhibitors, enzalutamide, Prior docetaxel
radium-223 other (yes vs no)
radionucleotides, hemibody Use of bone Enzalutamide 160 mg on
radiotherapy health agents®
+ No known brain or visceral
metastases
+ Primary endpoint: rPFS
+ Secondary endpoint: OS, DSS, SSE, time to initiation of next systemic antineoplastic therapy,
PFS2, BPI, EQ-5D-5L
* Bone heath agents (denosumab or brphosphonates) only permites in patients receiving them at bassline, ination during study prohibited to prevent confounding eects -
1. hpsiesniealialsgowstudyNCTO2194842.2. Gilessen S et a, ASCO 2021. Abstract 5002. ¡com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
PEACE-IIl: Decreased Fracture Rate by Mandating Bone-
Protecting Agents With Radium-223 Plus Enzalutamide’
Safety Update + Without BPA, fracture risk is increased
April 2021 + With BPA, the cumulative fracture incidence
is low for patients treated with either
combination therapy or enzalutamide alone
x
H
i Enza + Rad without BPA
Î
i Enza without BPA
é
Enza + Rad with BPA
Enza with BPA
PER °°" Time Since Randomization, ais
1 Guess 5 et at ASCO 2021. Absrat 5002 PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Protecting Agents With Radium-223 Plus Enzalutamide’
Safety Update + Without BPA, fracture risk is increased
April 2021 + With BPA, the cumulative fracture incidence
is low for patients treated with either
combination therapy or enzalutamide alone
x
H
i Enza + Rad without BPA
Î
i Enza without BPA
é
Enza + Rad with BPA
Enza with BPA
PER °°" Time Since Randomization, ais
1 Guess 5 et at ASCO 2021. Absrat 5002 PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
177Lu-PSMA-617 is now SOC for mCRPC post NHT and taxanes (phase 3 VISION)
177Lu-PSMA-617 and other beta-based RLTs are moving earlier in the disease paradigm
Localized
prostate cancer mHSPC mCRPC
Hormone sensitive
PSMAddition
VISION
PSMA-Based RLT Phase 3
PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
177Lu-PSMA-617 and other beta-based RLTs are moving earlier in the disease paradigm
Localized
prostate cancer mHSPC mCRPC
Hormone sensitive
PSMAddition
VISION
PSMA-Based RLT Phase 3
PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
177Lu-PSMA-617 Radioligand Therapy‘?
VISION Eligibility Criteria
+ mCRPC
‘71Lu-PSMA-617 binds to PSMA on
the cell membrane with high affinity
— Prior treatments:
= osent RAS
4 resume > 1or2taxane
- PS of 0-2
PSMA PET/CT+
Prostate cancer cell
and neighboring cell
pray Best SOC
"Lu-PSMA-617
(7.4 GBq Q6W x
4-6 cycles)
Best SOC
Primary endpoint: PFS, OS
+ Reduced binding inthe Kidneys, spleen, ve, salivary glands, lacrimal glands, submandibular glands, and bone marrow is expected e
1. Moris MJ et al ASCO 2021. Abstract LBA. 2. htps:/lnicaltials govistudyINCTO351 1684, PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
VISION Eligibility Criteria
+ mCRPC
‘71Lu-PSMA-617 binds to PSMA on
the cell membrane with high affinity
— Prior treatments:
= osent RAS
4 resume > 1or2taxane
- PS of 0-2
PSMA PET/CT+
Prostate cancer cell
and neighboring cell
pray Best SOC
"Lu-PSMA-617
(7.4 GBq Q6W x
4-6 cycles)
Best SOC
Primary endpoint: PFS, OS
+ Reduced binding inthe Kidneys, spleen, ve, salivary glands, lacrimal glands, submandibular glands, and bone marrow is expected e
1. Moris MJ et al ASCO 2021. Abstract LBA. 2. htps:/lnicaltials govistudyINCTO351 1684, PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
177Lu-PSMA-617 Plus Best SOC
Improved OS and rPFS in mCRPC15
*77Lu-PSMA-617 Improved OS
100
2 HR = 0.62 (95% Cl, 0.52-0.74); P< 001 (one-sided)
a" Median OS: 15.3 vs 11.3mo
= 70
¿o
FE]
5 «
$ ILu-PSMA-617 +
Fo SOC (n= 551)
20
SOC (n = 280)
0 24 6 8 10 12 14 16 18 20 22 24 26 28 30 32
Time From Randomization, mo
Both primary endpoints met: improved OS and rPFS in patients
with those receiving best SOC alone
Higher incidence of TEAEs with ‘7/Lu-PSMA-617 + SOC vs
‘7Lu-PSMA-617 Improved rPFS
100
2” HR = 0.40 (95% CI, 0.29.0 57); P < 001 (one-sided)
=e” Median (PFS: 8.7 vs 3.4 mo
337
¿to
EE]
Eso
E
LEE
330 LU-PSMAS17 +
a; SOC (n = 385)
5 SOC (n= 196)
0123456078 0 1010121594 151617 18102021
Time From Randomization, mo
77Lu-PSMA-617 + best SOC compared
OC, but treatment exposure was 23 times longer
PeerView.com/YWU827
in the 177Lu-PSMA-617 + SOC arm; exposure-adjusted safety analyses showed comparable findings for both arms
1. Sartor O eta. N Eng! J Med, 2021:365:1091-1103, 2. Chi KN et al, ASCO GU 2022, Abstract 85. 3, tos www da gov/ärugiresources-nformaton-approved-
rugs da-approves-pluvcto-metastac-castaton-esstant prostate-cancer. 4, Kuo Pet al ASCO 2022. Abstract 5002.5, Plvieo (utetum Lu 177 pote Preview
{evaxetan) Preserbing Information. is ww accessdat fda govirugsatida_docslabel2022/215833s0000 pat
Copyright © 2000-2024, PeerView
Improved OS and rPFS in mCRPC15
*77Lu-PSMA-617 Improved OS
100
2 HR = 0.62 (95% Cl, 0.52-0.74); P< 001 (one-sided)
a" Median OS: 15.3 vs 11.3mo
= 70
¿o
FE]
5 «
$ ILu-PSMA-617 +
Fo SOC (n= 551)
20
SOC (n = 280)
0 24 6 8 10 12 14 16 18 20 22 24 26 28 30 32
Time From Randomization, mo
Both primary endpoints met: improved OS and rPFS in patients
with those receiving best SOC alone
Higher incidence of TEAEs with ‘7/Lu-PSMA-617 + SOC vs
‘7Lu-PSMA-617 Improved rPFS
100
2” HR = 0.40 (95% CI, 0.29.0 57); P < 001 (one-sided)
=e” Median (PFS: 8.7 vs 3.4 mo
337
¿to
EE]
Eso
E
LEE
330 LU-PSMAS17 +
a; SOC (n = 385)
5 SOC (n= 196)
0123456078 0 1010121594 151617 18102021
Time From Randomization, mo
77Lu-PSMA-617 + best SOC compared
OC, but treatment exposure was 23 times longer
PeerView.com/YWU827
in the 177Lu-PSMA-617 + SOC arm; exposure-adjusted safety analyses showed comparable findings for both arms
1. Sartor O eta. N Eng! J Med, 2021:365:1091-1103, 2. Chi KN et al, ASCO GU 2022, Abstract 85. 3, tos www da gov/ärugiresources-nformaton-approved-
rugs da-approves-pluvcto-metastac-castaton-esstant prostate-cancer. 4, Kuo Pet al ASCO 2022. Abstract 5002.5, Plvieo (utetum Lu 177 pote Preview
{evaxetan) Preserbing Information. is ww accessdat fda govirugsatida_docslabel2022/215833s0000 pat
Copyright © 2000-2024, PeerView
Phase 3 VISION: 177Lu-PSMA-617 + SOC Delayed Time to
Worse
FACT-P Total Score
1%
essssaseé
3
3
É
&
ú
Time to Systematic
Skeletal Events
1.FizaziK tal. Lancet Oncol, 2023:24:587-610,
PeerView.com/YWU827
HR = 0.46
(95% Cl, 0.35.0.61); P <.001 (two-sided,
nominal, non-inferential analysis)
Median: 9.7 vs 2.4 mo
WILu-PSMA-617 + SOC (n = 385)
SOC alone (n = 196)
Time From Randomization, mo + ,
Event-Free Probability,
esusssazasó
g in HRQOL and Time to Skeletal Events!
BPI-SF Pain Intensity
HR = 0.45
(95% Cl, 0.33-0.60); P < .001 (two-sided,
nominal, non-inferential analysis)
Median: 14.3 vs 2.9 mo
"ILu-PSMA-617 + SOC (n = 385)
SOC alone (n = 196)
Event-Free Probability, %
Time From Randomization, mo
.50 (95% Cl, 0.40-0.62); P < 001 (two-sided)
Median: 11.5 vs 6.8 mo
Lu-PSMA-617 + SOC (n = 385)
tion, mo PeerView.com
Copyright © 2000-2024, PeerView
Worse
FACT-P Total Score
1%
essssaseé
3
3
É
&
ú
Time to Systematic
Skeletal Events
1.FizaziK tal. Lancet Oncol, 2023:24:587-610,
PeerView.com/YWU827
HR = 0.46
(95% Cl, 0.35.0.61); P <.001 (two-sided,
nominal, non-inferential analysis)
Median: 9.7 vs 2.4 mo
WILu-PSMA-617 + SOC (n = 385)
SOC alone (n = 196)
Time From Randomization, mo + ,
Event-Free Probability,
esusssazasó
g in HRQOL and Time to Skeletal Events!
BPI-SF Pain Intensity
HR = 0.45
(95% Cl, 0.33-0.60); P < .001 (two-sided,
nominal, non-inferential analysis)
Median: 14.3 vs 2.9 mo
"ILu-PSMA-617 + SOC (n = 385)
SOC alone (n = 196)
Event-Free Probability, %
Time From Randomization, mo
.50 (95% Cl, 0.40-0.62); P < 001 (two-sided)
Median: 11.5 vs 6.8 mo
Lu-PSMA-617 + SOC (n = 385)
tion, mo PeerView.com
Copyright © 2000-2024, PeerView
Phase 3 PSMAfore:
177Lu-PSMA-617 in Taxane-Naive mCRPC!
Key Eligibility Criteria
+ Confirmed progressive
- Not eligible for a PARPi
ECOG PS 0-1
Primary endpoint: rPFS
+ Key secondary endpoint: OS
+ Exploratory endpoints: ORR, DCR, DOR
1. Sartor © eta, ESMO 2029. LBA19.
PeerView.com/YWU827
mCRPC.
+ 21 PSMA-positive
metastatic lesion on Stratification
[*Ga]Ga-PSMA-11 PET/CT + Prior ARPI setting F
and no exclusionary PSMA- (castration- i
negative lesions resistant vs :
+ Progressed once on hormone-sensitive) À
second-generation ARPI + BPI-SF worst pain
— Candidate for change intensity score
in ARPI (0-3 vs >3)
+ Taxane-naive (except
[neoJadjuvant >12 mo ago)
Lu-PSMA-617
(200 mCi) + 10%
Crossover allowed
upon radiographic
progression by BICR
rPFS by BICR
Follow-up
ARPI change
abiraterone alutamid
PeerView.com
Copyright © 2000-2024, PeerView
177Lu-PSMA-617 in Taxane-Naive mCRPC!
Key Eligibility Criteria
+ Confirmed progressive
- Not eligible for a PARPi
ECOG PS 0-1
Primary endpoint: rPFS
+ Key secondary endpoint: OS
+ Exploratory endpoints: ORR, DCR, DOR
1. Sartor © eta, ESMO 2029. LBA19.
PeerView.com/YWU827
mCRPC.
+ 21 PSMA-positive
metastatic lesion on Stratification
[*Ga]Ga-PSMA-11 PET/CT + Prior ARPI setting F
and no exclusionary PSMA- (castration- i
negative lesions resistant vs :
+ Progressed once on hormone-sensitive) À
second-generation ARPI + BPI-SF worst pain
— Candidate for change intensity score
in ARPI (0-3 vs >3)
+ Taxane-naive (except
[neoJadjuvant >12 mo ago)
Lu-PSMA-617
(200 mCi) + 10%
Crossover allowed
upon radiographic
progression by BICR
rPFS by BICR
Follow-up
ARPI change
abiraterone alutamid
PeerView.com
Copyright © 2000-2024, PeerView
PSMAfore: Primary Endpoint of rPFS Met!
WLu-PSMA-617 ARPI Change
LL 234) (n = 234)
” 19 Events, n (%) 115 (49.1) 168 (71.8)
5 Median rPFS, mo 12.02 5.59
3 (95% CI) (230-1442) _(4.17-5.95)
23 6
2
E
8 40
CA Primary HR = 0.41 EUR tLu-PSMA-617
5 7 | (95% Cl, 0.29-0.56); P <.0001
úú | Updated HR = 0.43 (95% Cl, 0.33-0.54) ua ARPI change
o 2 4 6 8 0 2 6 8 2% 2
Time From Randomization, mo
No, at Risk
DAGA
m7 Bu Par "Be ae Pe a Be
1. Sartor O et al. ESMO 2023. Abstract LBAT3. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
WLu-PSMA-617 ARPI Change
LL 234) (n = 234)
” 19 Events, n (%) 115 (49.1) 168 (71.8)
5 Median rPFS, mo 12.02 5.59
3 (95% CI) (230-1442) _(4.17-5.95)
23 6
2
E
8 40
CA Primary HR = 0.41 EUR tLu-PSMA-617
5 7 | (95% Cl, 0.29-0.56); P <.0001
úú | Updated HR = 0.43 (95% Cl, 0.33-0.54) ua ARPI change
o 2 4 6 8 0 2 6 8 2% 2
Time From Randomization, mo
No, at Risk
DAGA
m7 Bu Par "Be ae Pe a Be
1. Sartor O et al. ESMO 2023. Abstract LBAT3. PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
PSMAfore: Third Interim OS Analysis!
“7Lu-PSMA-617 ARPI change
(n = 234) (n = 234)
HR = 0.98 (95% Cl, 0.75-1.28) Events, n (%) 104 (44.4) 112 (47.9)
Median,mo 23.66 23.85
(85% Cl) (19.75-NE) (20.6-26.55)
W"Lu-PSMA-617 Crossover:
134/234 (57.3%) in ARPI change group
1341173 (77.5%) eligible patients
ARPI change
Event-Free Probability, %
RPSFT crossover-adjusted OS analysis
0 2 4 6 E 1 à à à % me 30 à + HR=0.98 (95% CI, 0.76-1.27)
= _ Nodifference versus the ITT analysis because
‚mo RPSFT cannot adjust fo crossover confounding in
the context of ovetapping ITT curves
OS: HR <1 at third interim analysis with 73% information fraction
Intent-to-treat analysis
Ti
1.FizaziK eta, ASCO 2024, Abstract 5003, PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
“7Lu-PSMA-617 ARPI change
(n = 234) (n = 234)
HR = 0.98 (95% Cl, 0.75-1.28) Events, n (%) 104 (44.4) 112 (47.9)
Median,mo 23.66 23.85
(85% Cl) (19.75-NE) (20.6-26.55)
W"Lu-PSMA-617 Crossover:
134/234 (57.3%) in ARPI change group
1341173 (77.5%) eligible patients
ARPI change
Event-Free Probability, %
RPSFT crossover-adjusted OS analysis
0 2 4 6 E 1 à à à % me 30 à + HR=0.98 (95% CI, 0.76-1.27)
= _ Nodifference versus the ITT analysis because
‚mo RPSFT cannot adjust fo crossover confounding in
the context of ovetapping ITT curves
OS: HR <1 at third interim analysis with 73% information fraction
Intent-to-treat analysis
Ti
1.FizaziK eta, ASCO 2024, Abstract 5003, PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
PSMAfore: Time to HRQOL Worsening"
Prespecified analysis: Composite time to worsening in FACT-P, EQ-5D-5L, and
BPI-SF, including clinical progression and death
FACT-P Total Score? EQ-5D-5L Utility Score
Ie PSMASI7 ARP henge
'Lu-PSMA-S17 ARPI change
(n= 234 in= 234)
Events, n(%) 1670714) 187 (79.9) en Events, n(%) 1731739) 196 (63.8)
ek ‘Median, mo 748 427, Le Median, mo 614 388
a BE alto pm Eo BE utile adie
1° po
+ 17/Lu-PSMA-617 =
2° Ñ 2° ILu-PSMA-617
is ia
i i ns
ns * &
ass,
1: FizaziK et al. ASCO 2024, Abstract 5003, PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
Prespecified analysis: Composite time to worsening in FACT-P, EQ-5D-5L, and
BPI-SF, including clinical progression and death
FACT-P Total Score? EQ-5D-5L Utility Score
Ie PSMASI7 ARP henge
'Lu-PSMA-S17 ARPI change
(n= 234 in= 234)
Events, n(%) 1670714) 187 (79.9) en Events, n(%) 1731739) 196 (63.8)
ek ‘Median, mo 748 427, Le Median, mo 614 388
a BE alto pm Eo BE utile adie
1° po
+ 17/Lu-PSMA-617 =
2° Ñ 2° ILu-PSMA-617
is ia
i i ns
ns * &
ass,
1: FizaziK et al. ASCO 2024, Abstract 5003, PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, Peerview
PSMAfore: Pain Intensity’?
Time to Worsening in Pain Interference
ity, %
Time to Worsening in Pain Intensity” {7 Lu-PSMA-617
TLuPSMAS17 ARPI change
(m=234 2 n=230
100 Evens noe) 12039 182078)
Megan mo 565 371
RC) (457897) — (308440)
ity, %
re TLUPSMASIT ARPI change
so (n= 230) 1-23
O) ICH HR = 0.67 (05% CI, 0.54-0.83)
so Medanme 503 371
(RC) Men (0437
Event-Free Probal
so HR = 0.9 (65% C1.0.560.85) TA
u Time, mo
o % yon Time to Disease-Related Pain
3
o 2 4 6 6 0 2 ww 6 %® à
3 e] mupsmasız Lu PSMA-E17 ARPI change
Time, mo 3 EN zh
3 m Trans a) 182078) ws 8)
= san. mo 513 385
20 CEM
Ln HR = 0.70 65% C1,0.57.0.45)
Bo
Ce re)
Time, mo
+ second Inter OS anal. "Previous presented at ESMO 2023. 7
1. FiaziK etal. ASCO 2024, Abstract 5003, PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Time to Worsening in Pain Interference
ity, %
Time to Worsening in Pain Intensity” {7 Lu-PSMA-617
TLuPSMAS17 ARPI change
(m=234 2 n=230
100 Evens noe) 12039 182078)
Megan mo 565 371
RC) (457897) — (308440)
ity, %
re TLUPSMASIT ARPI change
so (n= 230) 1-23
O) ICH HR = 0.67 (05% CI, 0.54-0.83)
so Medanme 503 371
(RC) Men (0437
Event-Free Probal
so HR = 0.9 (65% C1.0.560.85) TA
u Time, mo
o % yon Time to Disease-Related Pain
3
o 2 4 6 6 0 2 ww 6 %® à
3 e] mupsmasız Lu PSMA-E17 ARPI change
Time, mo 3 EN zh
3 m Trans a) 182078) ws 8)
= san. mo 513 385
20 CEM
Ln HR = 0.70 65% C1,0.57.0.45)
Bo
Ce re)
Time, mo
+ second Inter OS anal. "Previous presented at ESMO 2023. 7
1. FiaziK etal. ASCO 2024, Abstract 5003, PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
177Lu-PSMA-617 AE Profile
Dry mouth (xerostomia)
Typically mild, reversible with
drinking extra water,
chewing gum, or sucking on
sugar-free candy
Myelosuppression
Check CBC before
each administration
177Lu-PSMA-617
safety considerations
Fatigue, nausea,
Radioactivity to others pain flare
PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Dry mouth (xerostomia)
Typically mild, reversible with
drinking extra water,
chewing gum, or sucking on
sugar-free candy
Myelosuppression
Check CBC before
each administration
177Lu-PSMA-617
safety considerations
Fatigue, nausea,
Radioactivity to others pain flare
PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Moving PSMA Radioligand Trials Earlier
PSMAddition (mHSPC): 177Lu-PSMA-617 With SOC vs SOC Alone’?
Patient Population
+ Untreated or minimally treated
mHSPC.
+ Appropriate SOC (ADT and ARPI)
+ PSMA-positive on [®*Ga]Ga-
PSMA-11 PET/CT
(N= 1,144)
Stratification
+ Disease volume
+ Age
+ Previous or
planned treatment
of primary tumor
Accrual
Crossover allowed
upon radiographic
progression
Completed
77Lu-PSMA-617
74
Key Eligibility Criteria
+ Adults with progressive mHSPC
+ 1-5 PSMA-posiive Mi lesion on PSMA PET
and negative conventional imaging
+ All metastatic lesions amenable to SBRT
+ PSADT <10 months.
Prior treatment of the prostate by RP or XRT
Bq (200 mCi
+SBRT
Long-term
follow-up
1. hits: cnicalras govstudyNCTOS720157. 2. Tagawa S et al. ASCO 2025. Abstract TPSS116. 3. tps cinicairials.goustuNCTOSG30414 PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
PSMAddition (mHSPC): 177Lu-PSMA-617 With SOC vs SOC Alone’?
Patient Population
+ Untreated or minimally treated
mHSPC.
+ Appropriate SOC (ADT and ARPI)
+ PSMA-positive on [®*Ga]Ga-
PSMA-11 PET/CT
(N= 1,144)
Stratification
+ Disease volume
+ Age
+ Previous or
planned treatment
of primary tumor
Accrual
Crossover allowed
upon radiographic
progression
Completed
77Lu-PSMA-617
74
Key Eligibility Criteria
+ Adults with progressive mHSPC
+ 1-5 PSMA-posiive Mi lesion on PSMA PET
and negative conventional imaging
+ All metastatic lesions amenable to SBRT
+ PSADT <10 months.
Prior treatment of the prostate by RP or XRT
Bq (200 mCi
+SBRT
Long-term
follow-up
1. hits: cnicalras govstudyNCTOS720157. 2. Tagawa S et al. ASCO 2025. Abstract TPSS116. 3. tps cinicairials.goustuNCTOSG30414 PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Targeting PSMA With a Combination of Antibodies Plus
Small Molecules or Other Isotopes: Potential for Synergy?
E PSMA-TAC (?25Ac-pelgifatamab) is a PSMA-targeted
antibody under study for treatment of patients with mCRPCS
— Potentiates the antitumor efficacy of darolutamide in
androgen-dependent and -independent prostate
cancer models®
PSMA-targeted radionuclide therapy
(PSMA-TRT) with alpha-radiolabeled
antibody 22Ac-J591 + beta-
radioligand 7Lu-PSMA-18T13
1311 (beta-emitting radioisotope) + + First-in-human phase 1 study evaluating a first-in-class
LNTH-1095 (PSMA-targeted ligand) + radioligand therapy, JNJ-64207, targeting human
enzalutamide in patients with kallikrein 2 (hK2), a novel target expressed on the cell
chemotherapy-naive mCRPC who surface of prostate cancer cells with restricted expression
have progressed on abiraterone' elsewhere) with an 225Ac-labeled antibody to treat patients
with mCRPC?
+ 1-2 doses of JNJ-6420 elicited profound and durable
\_biachemical and radiographie responses
1. Tagawa ST et a J Cin Oncol 2023 Nov 3 [Epub ahead of prin) 2. ps /cinicatrias gowstudyINCTO3270572.
3 hips Nu cincatials gov/studyNCTOASOBSE7. 4. tips Icinialals gov/studyNCTO3G39689. 5. ps cinicalrials govistudy/NCTOSOS2308. a
8. Schatz CA et al. AACR 2023. Abarat 5047. 7. Moris MJ et al ASCO 2024. Abstract 5010, PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Small Molecules or Other Isotopes: Potential for Synergy?
E PSMA-TAC (?25Ac-pelgifatamab) is a PSMA-targeted
antibody under study for treatment of patients with mCRPCS
— Potentiates the antitumor efficacy of darolutamide in
androgen-dependent and -independent prostate
cancer models®
PSMA-targeted radionuclide therapy
(PSMA-TRT) with alpha-radiolabeled
antibody 22Ac-J591 + beta-
radioligand 7Lu-PSMA-18T13
1311 (beta-emitting radioisotope) + + First-in-human phase 1 study evaluating a first-in-class
LNTH-1095 (PSMA-targeted ligand) + radioligand therapy, JNJ-64207, targeting human
enzalutamide in patients with kallikrein 2 (hK2), a novel target expressed on the cell
chemotherapy-naive mCRPC who surface of prostate cancer cells with restricted expression
have progressed on abiraterone' elsewhere) with an 225Ac-labeled antibody to treat patients
with mCRPC?
+ 1-2 doses of JNJ-6420 elicited profound and durable
\_biachemical and radiographie responses
1. Tagawa ST et a J Cin Oncol 2023 Nov 3 [Epub ahead of prin) 2. ps /cinicatrias gowstudyINCTO3270572.
3 hips Nu cincatials gov/studyNCTOASOBSE7. 4. tips Icinialals gov/studyNCTO3G39689. 5. ps cinicalrials govistudy/NCTOSOS2308. a
8. Schatz CA et al. AACR 2023. Abarat 5047. 7. Moris MJ et al ASCO 2024. Abstract 5010, PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Audience Q&A O z
Copyright © 2000-2024, PeerView
Copyright © 2000-2024, PeerView
Prostate Cancer Challenge
Where in Chicago would you find this?
Grant Park
Lincoln Park
Millennium Park
Hyde Park
Copyright © 2000-2024, PeerView
Where in Chicago would you find this?
Grant Park
Lincoln Park
Millennium Park
Hyde Park
Copyright © 2000-2024, PeerView
ES
Panel Discussion
PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Panel Discussion
PeerView.com
PeerView.com/YWU827 Copyright © 2000-2024, PeerView
Resources to Provide Your Patients
ZERO:
National Leader in
Prostate Cancer Advocacy
Starting with education, ZERO offers
comprehensive support, providing millions
of patients and their families with disease
information through its website, printed
materials, videos, and webinars
PeerView.com/YWU827
Reputable information can:
+ Empower patients to participate in
shared decision-making
+ Help patients navigate issues
surrounding the impact of therapies
on their day-to-day life
Providers can direct their patients to
these groups for helpful resources
+ ZERO Prostate Cancer
+ Prostate Conditions Education Council
(PCEC)
+ American Cancer Society
+ Prostate Cancer Foundation (PCF)
+ NCCN Guidelines for Patients
PeerView.com
Copyright © 2000-2024, PeerView
ZERO:
National Leader in
Prostate Cancer Advocacy
Starting with education, ZERO offers
comprehensive support, providing millions
of patients and their families with disease
information through its website, printed
materials, videos, and webinars
PeerView.com/YWU827
Reputable information can:
+ Empower patients to participate in
shared decision-making
+ Help patients navigate issues
surrounding the impact of therapies
on their day-to-day life
Providers can direct their patients to
these groups for helpful resources
+ ZERO Prostate Cancer
+ Prostate Conditions Education Council
(PCEC)
+ American Cancer Society
+ Prostate Cancer Foundation (PCF)
+ NCCN Guidelines for Patients
PeerView.com
Copyright © 2000-2024, PeerView
Prostate Cancer Challenge
And the winner is ...
And the winner is ...
Download
Download Slideshow Get the original presentation fileQuick Actions
Statistics
- Views 17
- Slides 93
- Age 551 days
Related Slideshows
11
8-top-ai-courses-for-customer-support-representatives-in-2025.pptx
JeroenErne2
86 views
10
7-essential-ai-courses-for-call-center-supervisors-in-2025.pptx
JeroenErne2
80 views
13
25-essential-ai-courses-for-user-support-specialists-in-2025.pptx
JeroenErne2
76 views
11
8-essential-ai-courses-for-insurance-customer-service-representatives-in-2025.pptx
JeroenErne2
62 views
21
Know for Certain
DaveSinNM
38 views
17
PPT OPD LES 3ertt4t4tqqqe23e3e3rq2qq232.pptx
novasedanayoga46
41 views