Modern Team-Based Therapeutic Management for Bladder Cancer Care: Expert Strategies for Integrating the Latest Evidence and Treatment Advances
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May 14, 2024
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About This Presentation
Co-Chairs, Sia Daneshmand, MD, and Matthew D. Galsky, MD, discuss bladder cancer in this CME/MOC/NCPD/AAPA/IPCE activity titled “Modern Team-Based Therapeutic Management for Bladder Cancer Care: Expert Strategies for Integrating the Latest Evidence and Treatment Advances.” For the full presentat...
Slide Content
Modern Team-Based Therapeutic
Management for Bladder Cancer Care
Expert Strategies for Integrating the
Latest Evidence and Treatment Advances
Sia Daneshmand, MD [Y Matthew D. Galsky, MD
Professor of Urology and Medicine (Oncology) x
Professor of Medicine
Clinical Scholar 5 Icahn School of Medicine at Mount Sinai
Director of Urologic Oncology Director of Genitourinary Medical Oncology
USC Norris Comprehensive Cancer Center
Co-Leader, Cancer Clinical Investigation Program
Los Angeles, California
Associate Director for Translational Research
Tisch Cancer Institute
New York, New York
Go online to access full CME/MOC/NCPD/AAPA/IPCE information, including faculty disclosures.
2000-2024, PeerView
Management for Bladder Cancer Care
Expert Strategies for Integrating the
Latest Evidence and Treatment Advances
Sia Daneshmand, MD [Y Matthew D. Galsky, MD
Professor of Urology and Medicine (Oncology) x
Professor of Medicine
Clinical Scholar 5 Icahn School of Medicine at Mount Sinai
Director of Urologic Oncology Director of Genitourinary Medical Oncology
USC Norris Comprehensive Cancer Center
Co-Leader, Cancer Clinical Investigation Program
Los Angeles, California
Associate Director for Translational Research
Tisch Cancer Institute
New York, New York
Go online to access full CME/MOC/NCPD/AAPA/IPCE information, including faculty disclosures.
2000-2024, PeerView
Our Goals for Today
Increase your understanding of current and emerging data for the
treatment of bladder cancer utilizing bladder-sparing and
perioperative approaches, advanced drug delivery techniques, and
modern immunotherapy regimens
Equip you with the skills you need to implement these approaches
into personalized treatment plans
Provide you with guidance on how to support team-based
management of the unique suite of adverse events associated with
various regimens
2000-2024, PeerView
Increase your understanding of current and emerging data for the
treatment of bladder cancer utilizing bladder-sparing and
perioperative approaches, advanced drug delivery techniques, and
modern immunotherapy regimens
Equip you with the skills you need to implement these approaches
into personalized treatment plans
Provide you with guidance on how to support team-based
management of the unique suite of adverse events associated with
various regimens
2000-2024, PeerView
Unmet Needs in the Treatment of NMIBC and MIBC
+ Only one-third of patients with NMIBC are given intravesical BCG" à
— BCG shortages in the United States may affect access?
+ Close to half of patients with MIBC worldwide may not receive curative
intent therapy?
+ Patients who have undergone radical cystectomy for MIBC often have
impaired HRQOL and a high risk of recurrence*> A
« Development of effective, safe, and durable intravesical treatment remains a
critical unmet clinical need for patients who want to avoid radical cystectomy
+ Effective approaches post-radical cystectomy are key to lessening risk
of recurrence )
1. Tyson Meta. J Cin Oncol. 2019:37(suppl 1SJ:e18012. 2. ps www auanet.orglabout-unbeg-shetage-ino. m
3. Westergren DO et a. J Urol, 2019.202.905-912. 4. Choi Het al. Trans! Ando! Uo, 2020:9-2997-3006. 5, Roupret Met al. Eur Url 2021:79:5279. PeerView.com
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
+ Only one-third of patients with NMIBC are given intravesical BCG" à
— BCG shortages in the United States may affect access?
+ Close to half of patients with MIBC worldwide may not receive curative
intent therapy?
+ Patients who have undergone radical cystectomy for MIBC often have
impaired HRQOL and a high risk of recurrence*> A
« Development of effective, safe, and durable intravesical treatment remains a
critical unmet clinical need for patients who want to avoid radical cystectomy
+ Effective approaches post-radical cystectomy are key to lessening risk
of recurrence )
1. Tyson Meta. J Cin Oncol. 2019:37(suppl 1SJ:e18012. 2. ps www auanet.orglabout-unbeg-shetage-ino. m
3. Westergren DO et a. J Urol, 2019.202.905-912. 4. Choi Het al. Trans! Ando! Uo, 2020:9-2997-3006. 5, Roupret Met al. Eur Url 2021:79:5279. PeerView.com
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
Team-Based Care of Patients With Bladder Cancer
Numerous FDA-approved agents and clinical trials underway
have changed the approach to management of bladder cancer
across the disease continuum
Urologists, who are often the first
point of contact for patients, need
to be familiar with the range of
treatment options at various
disease stages
Patient education must focus
on the importance of prompt
recognition and management
of AEs
PeerView.com/XSE827
PeerView.com
Copyright © 2000-2024, Peerview
Numerous FDA-approved agents and clinical trials underway
have changed the approach to management of bladder cancer
across the disease continuum
Urologists, who are often the first
point of contact for patients, need
to be familiar with the range of
treatment options at various
disease stages
Patient education must focus
on the importance of prompt
recognition and management
of AEs
PeerView.com/XSE827
PeerView.com
Copyright © 2000-2024, Peerview
BCAN Is an Excellent Resource for
Professionals, Patients, and Care:
When diagnosed with bladder cancer,
I patients and their caregivers may feel
7 overwhelmed by the amount of treatment
BCAN. options for urothelial carcinoma. BCAN
Buster ame noch PrOVides educational resources to help
nang the may core ondo cue ti We: bladder cancer patients
in patients feel more prepared. We ge bladder cancer tients
Support they need 19 cope with
In addition to giving patients and caregivers support to cope with the tha deta.
disease, BCAN also offers free resources for healthcare providers
to share with patients:
+ Printed materials + Podcasts + Bladder Cancer Support Line:
+ Animated videos + Treatment matrix call (833-ASK-4-BCA)
+ Webinars + Clinical trials dashboard
See the BCAN Practice Aid for full details on
the BCAN website, a QR code for professionals
to download resources for patients, and more!
PeerView.com
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
Professionals, Patients, and Care:
When diagnosed with bladder cancer,
I patients and their caregivers may feel
7 overwhelmed by the amount of treatment
BCAN. options for urothelial carcinoma. BCAN
Buster ame noch PrOVides educational resources to help
nang the may core ondo cue ti We: bladder cancer patients
in patients feel more prepared. We ge bladder cancer tients
Support they need 19 cope with
In addition to giving patients and caregivers support to cope with the tha deta.
disease, BCAN also offers free resources for healthcare providers
to share with patients:
+ Printed materials + Podcasts + Bladder Cancer Support Line:
+ Animated videos + Treatment matrix call (833-ASK-4-BCA)
+ Webinars + Clinical trials dashboard
See the BCAN Practice Aid for full details on
the BCAN website, a QR code for professionals
to download resources for patients, and more!
PeerView.com
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
Background
High-risk NMIBC is defined as high-grade Ta, any T1, and/or carcinoma in situ (CIS)
+ Standard of care for high-risk NMIBC: TURBT followed by intravesical BCG
+ Prognosis is poor for patients whose disease does not respond to BCG or relapses within 12 months’;
these patients are directed to radical cystectomy
Criteria for the definition of adequate BCG and BCG-unresponsive, high-risk NMIBC are well
established and endorsed by the FDA?
+ Adequate BCG induction: 25 instillations of BCG and 27 instillations within 9 months of the first
instillation of induction therapy
+ BCG-unresponsive, high-risk NMIBC is defined as one of the following:
— Stage progression at 3 months despite adequate BCG induction
— High-grade T1 disease at first evaluation after adequate BCG induction
— Persistent high-risk NMIBC at 6 months after adequate BCG
— Recurrent high-risk NMIBC within 9 months of the last BCG instillation despite adequate BCG
1. Jeong et a. BMC Cancer 202222361. 2. Kamat AM et al. J Cin Oncol 2016:34:1935-1944, PeerView.com
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
High-risk NMIBC is defined as high-grade Ta, any T1, and/or carcinoma in situ (CIS)
+ Standard of care for high-risk NMIBC: TURBT followed by intravesical BCG
+ Prognosis is poor for patients whose disease does not respond to BCG or relapses within 12 months’;
these patients are directed to radical cystectomy
Criteria for the definition of adequate BCG and BCG-unresponsive, high-risk NMIBC are well
established and endorsed by the FDA?
+ Adequate BCG induction: 25 instillations of BCG and 27 instillations within 9 months of the first
instillation of induction therapy
+ BCG-unresponsive, high-risk NMIBC is defined as one of the following:
— Stage progression at 3 months despite adequate BCG induction
— High-grade T1 disease at first evaluation after adequate BCG induction
— Persistent high-risk NMIBC at 6 months after adequate BCG
— Recurrent high-risk NMIBC within 9 months of the last BCG instillation despite adequate BCG
1. Jeong et a. BMC Cancer 202222361. 2. Kamat AM et al. J Cin Oncol 2016:34:1935-1944, PeerView.com
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
KEYNOTE-057 Cohort A: Pembrolizumab Monotherapy for
BCG-Unresponsive, High-Risk NMIBC'
Cohort A: CIS + Papillary Disease (High-Grade Ta or T1)
Patients (N
n (%) EX
CR 39 (40.6) 30.7-51.1
Non-CR 56(583) 47.8-68.3
Progression to T2 0 NA
NE 141.0) 05.7
+ Upstaging to 2pT2 in 8.3% of patients
Extended minimum follow-up of 26.3 mo
+ Of 39 responders, 13 (33.3%) remained in CR
218 mo and 9 (23.1%) remained in CR 224 mo
A as of the data cutoff date
+ No new safety risks were identified
Patients Remaining in CR, %
Pembrolizumab was FDA approved for the treatment of patients with BCG-unresponsive, high-risk NMIBC
with CIS with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy
1. Balar AV et al Lancet Oncol, 202122919930. PeerView.com
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
BCG-Unresponsive, High-Risk NMIBC'
Cohort A: CIS + Papillary Disease (High-Grade Ta or T1)
Patients (N
n (%) EX
CR 39 (40.6) 30.7-51.1
Non-CR 56(583) 47.8-68.3
Progression to T2 0 NA
NE 141.0) 05.7
+ Upstaging to 2pT2 in 8.3% of patients
Extended minimum follow-up of 26.3 mo
+ Of 39 responders, 13 (33.3%) remained in CR
218 mo and 9 (23.1%) remained in CR 224 mo
A as of the data cutoff date
+ No new safety risks were identified
Patients Remaining in CR, %
Pembrolizumab was FDA approved for the treatment of patients with BCG-unresponsive, high-risk NMIBC
with CIS with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy
1. Balar AV et al Lancet Oncol, 202122919930. PeerView.com
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Gene Therapy for NMIBC
Nadofaragene Firadenovec
A nonreplicating adenoviral
vector-based gene therapy
that delivers human
IFNa2b-complementary
DNA to urothelial cells and
Syn3 to enhance viral
transduction to the
urothelium. IFNa2b-
complementary DNA is
transcribed into IFNa2b
protein in bladder epithelial
cells, where it exhibits
direct and indirect
immunomodulatory effects
inhibiting tumor growth"?
1. Bootjan SA etal Lancet Oncol. 2021:22:107-117. 2. Boorjan SA etal. SUO 2023. Abstract TPS7OS. 3. Narayan VM et a. Front Oncol 2024:14:1350725.
PeerView.com/XSE827
PeerView.com
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Nadofaragene Firadenovec
A nonreplicating adenoviral
vector-based gene therapy
that delivers human
IFNa2b-complementary
DNA to urothelial cells and
Syn3 to enhance viral
transduction to the
urothelium. IFNa2b-
complementary DNA is
transcribed into IFNa2b
protein in bladder epithelial
cells, where it exhibits
direct and indirect
immunomodulatory effects
inhibiting tumor growth"?
1. Bootjan SA etal Lancet Oncol. 2021:22:107-117. 2. Boorjan SA etal. SUO 2023. Abstract TPS7OS. 3. Narayan VM et a. Front Oncol 2024:14:1350725.
PeerView.com/XSE827
PeerView.com
Copyright © 2000-2024, PeerView
Gene Therapy for NMIBC: Phase 3 ADSTILADRIN*2
+ First gene therapy approved by the FDA for the treatment of adult patients with high-
isk BCG-
unresponsive NMIBC with CIS with or without papillary tumors (December 2022)
Initial report:
+ 55/103 (53.4%) patients with CIS (+ high-grade
Ta or T1 tumor) had a CR within 3 mo of first dose
+ Response was maintained in 25/55 (45.5%)
patients at 12 mo
36-month follow-up:
+ MDOCR: 9.7 mo
+ Probability of maintaining a CR for
236 mo: 34.2%
+ 36-mo cystectomy-free survival rate: 53.8%
+ 3-year OS rate: 90.4%
Intravesical nadofaragene firadenovec,
administered once every 3 mo,
demonstrated a sustained durability of
initial CR in approximately 25% of patients EEE
with BCG-unresponsive CIS + Ta/T1 Time From First Nadofaragene
Papillary disease through 36 mo Firadenovec Administration, mo
Proportion of Patients, %
1. Bootjan SA etal, Lancet Oncol. 2021:22:107-117. 2. Boorjan SA etal, SUO 2023, Abstract TPS7OS.
PeerView.com/XSE827
Patients Free From High-Grade Recurrence
(n= 103)
Proportion of Patients, %
36-Month Efficacy of Nadofaragene Firadenovec in Patients
With BCG-Unresponsive CIS + Ta/T1 (Efficacy Analysis Set)
DOCR
(n=55)
5 6 8 2 2 3
Time From First Nadofaragene
Firadenovec Administration, mo
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Copyright © 2000-2024, PeerView
+ First gene therapy approved by the FDA for the treatment of adult patients with high-
isk BCG-
unresponsive NMIBC with CIS with or without papillary tumors (December 2022)
Initial report:
+ 55/103 (53.4%) patients with CIS (+ high-grade
Ta or T1 tumor) had a CR within 3 mo of first dose
+ Response was maintained in 25/55 (45.5%)
patients at 12 mo
36-month follow-up:
+ MDOCR: 9.7 mo
+ Probability of maintaining a CR for
236 mo: 34.2%
+ 36-mo cystectomy-free survival rate: 53.8%
+ 3-year OS rate: 90.4%
Intravesical nadofaragene firadenovec,
administered once every 3 mo,
demonstrated a sustained durability of
initial CR in approximately 25% of patients EEE
with BCG-unresponsive CIS + Ta/T1 Time From First Nadofaragene
Papillary disease through 36 mo Firadenovec Administration, mo
Proportion of Patients, %
1. Bootjan SA etal, Lancet Oncol. 2021:22:107-117. 2. Boorjan SA etal, SUO 2023, Abstract TPS7OS.
PeerView.com/XSE827
Patients Free From High-Grade Recurrence
(n= 103)
Proportion of Patients, %
36-Month Efficacy of Nadofaragene Firadenovec in Patients
With BCG-Unresponsive CIS + Ta/T1 (Efficacy Analysis Set)
DOCR
(n=55)
5 6 8 2 2 3
Time From First Nadofaragene
Firadenovec Administration, mo
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Full Availability of Nadofaragene Firadenovec'
December 2022: FDA approval
Manufacturing to create full product supply
September 2023: Early Experience Program to clinical trial sites
that participated in the phase 3 study and community clinics with
the highest number of appropriate patients with NMIBC
January 2024: Full product supply available ahead of schedule
1. Narayan VM etal, Front Oncol, 2024:14:1359725, PeerView.com
XSE827 Copyright
December 2022: FDA approval
Manufacturing to create full product supply
September 2023: Early Experience Program to clinical trial sites
that participated in the phase 3 study and community clinics with
the highest number of appropriate patients with NMIBC
January 2024: Full product supply available ahead of schedule
1. Narayan VM etal, Front Oncol, 2024:14:1359725, PeerView.com
XSE827 Copyright
Gene Therapy for NMIBC: Real-World Use
Phase 4 ADSTILADRIN in BLadder CancEr (ABLE-41) US Real World Evidence Study!
N~200
+ Adults 218 years
+ Planned enroliment at -50 US urology sites
Key exclusion criteria
+ Patients who received nadofaragene
firadenovec in a previous clinical trial
Key inclusion criteria
+ Patients treated with nadofaragene
(e FPFV was in September 2023 fradenovec at physician diseretion ||. Patients currently enrolled in a clinical tral
Index date Subsequent nadofaragene firadenovec:
PAWAn endpoint: first nadofaragene doses approximately Q3M
CRrate
Baseline and Enrollment
demographic nadofaragene
data
Patient and care
at each routine
1 month after
first dose
1. Daneshmand S et ai. ASCO GU 2024, Abstract TPS7OS PeerView.com
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
Phase 4 ADSTILADRIN in BLadder CancEr (ABLE-41) US Real World Evidence Study!
N~200
+ Adults 218 years
+ Planned enroliment at -50 US urology sites
Key exclusion criteria
+ Patients who received nadofaragene
firadenovec in a previous clinical trial
Key inclusion criteria
+ Patients treated with nadofaragene
(e FPFV was in September 2023 fradenovec at physician diseretion ||. Patients currently enrolled in a clinical tral
Index date Subsequent nadofaragene firadenovec:
PAWAn endpoint: first nadofaragene doses approximately Q3M
CRrate
Baseline and Enrollment
demographic nadofaragene
data
Patient and care
at each routine
1 month after
first dose
1. Daneshmand S et ai. ASCO GU 2024, Abstract TPS7OS PeerView.com
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
What’s Next? Investigational Strategies for NMIBC
Phase 3 POTOMAC!
High-Risk NMIBC
+ Any HG
+ Any T1
+ Multiple, recurrent and large (>3 cm) Ta
+ No prior BCG therapy
BCG indu
BCG BCG induction/
induction only [| maintenance
+durvalumab # + durvalumab
maintenance
(24 mo)
+ Primary endpoint: DFS
1. Mips:/cicalias govistudyiNCTO3526604, 2, htpsi/lncaltials govistudyINCTO37 11032,
PeerView.com/XSE827
Phase 3 KEYNOTE-676?
High-Risk NMIBC
+ Recurrence after induction
BCG therapy only
BCG +
pembrolizumab
+ Primary endpoint: CR in patients with CIS
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Phase 3 POTOMAC!
High-Risk NMIBC
+ Any HG
+ Any T1
+ Multiple, recurrent and large (>3 cm) Ta
+ No prior BCG therapy
BCG indu
BCG BCG induction/
induction only [| maintenance
+durvalumab # + durvalumab
maintenance
(24 mo)
+ Primary endpoint: DFS
1. Mips:/cicalias govistudyiNCTO3526604, 2, htpsi/lncaltials govistudyINCTO37 11032,
PeerView.com/XSE827
Phase 3 KEYNOTE-676?
High-Risk NMIBC
+ Recurrence after induction
BCG therapy only
BCG +
pembrolizumab
+ Primary endpoint: CR in patients with CIS
PeerView.com
Copyright © 2000-2024, PeerView
What’s Next? Investigational Strategies for NMIBC
Oncolytic adenovirus: cretostimogene grenadenorepvec (CG0070)
+ Ad5-based oncolytic vaccine engineered to express GM-CSF and replicate selectively in tumor cells
with mutated or deficient RB
Phase 3 BOND-003 Trial! Cretostimogene
intravesical CG0070 monotherapy | Response Evaluation Monotherapy
for patients with high-risk BCG- % (nIN) 95% Cl
unresponsive NMIBC
Any time 75.7 (50/66) 63-85
3mo 68.2 (45/66) 55-79
6 mo 63.6 (42/66) 51-75
DOCR
23 mo 84.0 (42/50) 70-92
26 mo 74.4 (32/43) 58-86
1. Tyson MO et al. SUO 2023. Abstract 3366, PeerView.com
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
Oncolytic adenovirus: cretostimogene grenadenorepvec (CG0070)
+ Ad5-based oncolytic vaccine engineered to express GM-CSF and replicate selectively in tumor cells
with mutated or deficient RB
Phase 3 BOND-003 Trial! Cretostimogene
intravesical CG0070 monotherapy | Response Evaluation Monotherapy
for patients with high-risk BCG- % (nIN) 95% Cl
unresponsive NMIBC
Any time 75.7 (50/66) 63-85
3mo 68.2 (45/66) 55-79
6 mo 63.6 (42/66) 51-75
DOCR
23 mo 84.0 (42/50) 70-92
26 mo 74.4 (32/43) 58-86
1. Tyson MO et al. SUO 2023. Abstract 3366, PeerView.com
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
Advances in Therapeutic Strategies for NMIBC:
TAR-200 Intravesical Drug Delivery
TAR-200
Intravesical drug delivery system that enables a sustained release of gemcitabine
into the bladder, increasing the dwell time of the local drug concentration
Phase 2 SunRISe-112
Key Eligibility Criteria
+ BCG-unresponsive, high-risk NMIBC
SES 02 Cohort 2: TAR-200* (N = 80)
+ With or without papillary disease
(TA, high-grade Ta)
Cohort 3: Cetrelimab (N = 50)
Cohort closed
Cohort 4: TAR-200* (N = 50)
+ Ineligible for or declined RC
* TAR-20 goung BW (vein) or rs wees en OTZW tough we ñ
1. ps ina ge MOTOAGADEZS. 2 Daneshmand Seal AUX 2023 LEA 02403, 3. Neceh Ae al: ESMO 2023, BAJOS, PeerView.com
Primary endpoint:
Overall CR rate
Key secondary
endpoints:
DOR, OS, safety
Primary endpoint:
Key Eligibility Criteria
DFS rate
+ HRNMIBC papillary disease only (no CIS)
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
TAR-200 Intravesical Drug Delivery
TAR-200
Intravesical drug delivery system that enables a sustained release of gemcitabine
into the bladder, increasing the dwell time of the local drug concentration
Phase 2 SunRISe-112
Key Eligibility Criteria
+ BCG-unresponsive, high-risk NMIBC
SES 02 Cohort 2: TAR-200* (N = 80)
+ With or without papillary disease
(TA, high-grade Ta)
Cohort 3: Cetrelimab (N = 50)
Cohort closed
Cohort 4: TAR-200* (N = 50)
+ Ineligible for or declined RC
* TAR-20 goung BW (vein) or rs wees en OTZW tough we ñ
1. ps ina ge MOTOAGADEZS. 2 Daneshmand Seal AUX 2023 LEA 02403, 3. Neceh Ae al: ESMO 2023, BAJOS, PeerView.com
Primary endpoint:
Overall CR rate
Key secondary
endpoints:
DOR, OS, safety
Primary endpoint:
Key Eligibility Criteria
DFS rate
+ HRNMIBC papillary disease only (no CIS)
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
Phase 2 SunRISe-1: BCG-Unresponsive,
High-Risk NMIBC14
Median DOR has not been reached
Median follow-up in responders was 48 wk (range, 12-21)
Kaplan-Meier estimates for DOR rate
+ 6 mo: 93% (95% Cl, 61-99)
+ 12 mo: 84% (95% Cl, 49-96)
Overall CR Rate, %
Patients (N = 54)
91% (21/23) responses are ongoing
+ 11 patents had DOR 26 mo (10/11 ongoing)
+ 6 patents had DOR 212 mo (al ongoing)
"None ofthe patents with CR have undergone
radeal cystectomy
Centrally Assessed Investigator Assessed
(n= 30% (n= 30)
+ TAR-200 was well tolerated; mainly low-grade 1 or 2
AEs, with manageable urinary symptoms
+ TAR-200-related SAEs, grade 23 AEs, and
discontinuations were infrequent D os 8 8 À 8 © À À À
Time, mo
+ Overat GR rates based on CR at any Eme. * The eficacy analysis was performed on al reted patents who have active disease a baseline and adequate disease
‘assessment post baseine a who have progressed, died due to recurence o highisk disease o progressive disease, or have discontinued the study
RGR is defned as having a negative cystoscopy and negative (ncludng atypical) cenvaly read une tology or poste cystoscopy wth Biopsy proven benign or
low-grade NMIBC and negative (ncluing atypical central read cytology at any tme point
1 tp inicatils.govstudyNCTO4840823. 2. Daneshmand 5 etal AUA 2023. LBA 02-03, 3. Necehi A e al. ESMO 2023. LBAIOS, N
4! Jacob Jet al. AUA 2024, Abstract P20 PeerView.com
= On treatment
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
High-Risk NMIBC14
Median DOR has not been reached
Median follow-up in responders was 48 wk (range, 12-21)
Kaplan-Meier estimates for DOR rate
+ 6 mo: 93% (95% Cl, 61-99)
+ 12 mo: 84% (95% Cl, 49-96)
Overall CR Rate, %
Patients (N = 54)
91% (21/23) responses are ongoing
+ 11 patents had DOR 26 mo (10/11 ongoing)
+ 6 patents had DOR 212 mo (al ongoing)
"None ofthe patents with CR have undergone
radeal cystectomy
Centrally Assessed Investigator Assessed
(n= 30% (n= 30)
+ TAR-200 was well tolerated; mainly low-grade 1 or 2
AEs, with manageable urinary symptoms
+ TAR-200-related SAEs, grade 23 AEs, and
discontinuations were infrequent D os 8 8 À 8 © À À À
Time, mo
+ Overat GR rates based on CR at any Eme. * The eficacy analysis was performed on al reted patents who have active disease a baseline and adequate disease
‘assessment post baseine a who have progressed, died due to recurence o highisk disease o progressive disease, or have discontinued the study
RGR is defned as having a negative cystoscopy and negative (ncludng atypical) cenvaly read une tology or poste cystoscopy wth Biopsy proven benign or
low-grade NMIBC and negative (ncluing atypical central read cytology at any tme point
1 tp inicatils.govstudyNCTO4840823. 2. Daneshmand 5 etal AUA 2023. LBA 02-03, 3. Necehi A e al. ESMO 2023. LBAIOS, N
4! Jacob Jet al. AUA 2024, Abstract P20 PeerView.com
= On treatment
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
SunRISe-3: BCG-Naive, High-Risk NMIBC*
Key Elig iteri Ela Group A (n = 350)
TAR-200 (gemcitabine 225 mg Q3W [induction phase]
TO and Q12W [maintenance phase]) + cetrelimab
(high-grade Ta, any T1, or CIS)" SET
BCG-naive (no prior BCG, or QW for 6 wk [induction] and QW for
last exposure >3 y prior to 96 [maintenal
randomization)
Age 218 y Group C (n = 350)
ECOG PS 0-2 TAR-200 (gemcitabine 225 mg Q3W [induction phase]
N = 1,050 and Q12W [maintenance phase])
Primary endpoint: EFS (time from randomization to first occurrence of HR disease, progression,»
or any-cause death, whichever occurs first®)
Secondary endpoints: overall CR rate (CIS only)/duration of CR,* RFS, TTP, OS, cancer-specific
survival, safety and tolerability, patient-reported outcomes
A able pay soso must be iy resaca (bean) rico randomization end document BL. esecpy: ca ine coo at screning must be negate or pica or
grace UC in Pants wth paplayıany dasase, Al AEs asocalaó wih any prior surgery ander raves erapy must have resaves fo CTCAE v5. grade <2 pio randomization
"Poren deine a sage crease to Ta 13T ox tom Gis 1o T1 progre lo MBG (122) or mph node (Ws) or ants) ease, cave seers Wak
For patents wih CI. poster! este at mol aso considered an EFS event © patents win CS wha have no presence of HR star a6 mo
“Time rom rt CR cave to fst erden ol recurrence progression, or anyrcaue sath, whichever cere 7
1. ps einicalials govistudy/NCTOS7 14202. PeerView.com
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Key Elig iteri Ela Group A (n = 350)
TAR-200 (gemcitabine 225 mg Q3W [induction phase]
TO and Q12W [maintenance phase]) + cetrelimab
(high-grade Ta, any T1, or CIS)" SET
BCG-naive (no prior BCG, or QW for 6 wk [induction] and QW for
last exposure >3 y prior to 96 [maintenal
randomization)
Age 218 y Group C (n = 350)
ECOG PS 0-2 TAR-200 (gemcitabine 225 mg Q3W [induction phase]
N = 1,050 and Q12W [maintenance phase])
Primary endpoint: EFS (time from randomization to first occurrence of HR disease, progression,»
or any-cause death, whichever occurs first®)
Secondary endpoints: overall CR rate (CIS only)/duration of CR,* RFS, TTP, OS, cancer-specific
survival, safety and tolerability, patient-reported outcomes
A able pay soso must be iy resaca (bean) rico randomization end document BL. esecpy: ca ine coo at screning must be negate or pica or
grace UC in Pants wth paplayıany dasase, Al AEs asocalaó wih any prior surgery ander raves erapy must have resaves fo CTCAE v5. grade <2 pio randomization
"Poren deine a sage crease to Ta 13T ox tom Gis 1o T1 progre lo MBG (122) or mph node (Ws) or ants) ease, cave seers Wak
For patents wih CI. poster! este at mol aso considered an EFS event © patents win CS wha have no presence of HR star a6 mo
“Time rom rt CR cave to fst erden ol recurrence progression, or anyrcaue sath, whichever cere 7
1. ps einicalials govistudy/NCTOS7 14202. PeerView.com
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FGFR Mutations Are Frequently Observed
in Bladder Cancer!
Non-Muscle Invasive Muscle Invasive Metastatic
>60% ~30% ~30% ~20%
L
| FGFR inhibitors can be effective across the disease spectrum
1. Knowles MA et al. Nat Rev Cancer 2015:15 25-41 PeerView.com
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in Bladder Cancer!
Non-Muscle Invasive Muscle Invasive Metastatic
>60% ~30% ~30% ~20%
L
| FGFR inhibitors can be effective across the disease spectrum
1. Knowles MA et al. Nat Rev Cancer 2015:15 25-41 PeerView.com
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Importance of Discussing Genomic Testing With Patients
testing for genomic alterations
+ Flatiron database analysis of >700 eligible patients showed that fewer
than half had undergone testing!
— Of those who were tested, 21% had an FGFR mutation but only
42% received erdafitinib'
— Options include specifically testing tumors for FGFR3 alterations
(eg, RT-PCR companion assay) or more comprehensive approaches
(eg, NGS panels, liquid biopsy)
The goal is to offer patients the full range of available therapeutic
options to ensure the best possible outcome
1.Nimgaonkar Net al. JAMA Oncol 2022::1070-1072. PeerView.com
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testing for genomic alterations
+ Flatiron database analysis of >700 eligible patients showed that fewer
than half had undergone testing!
— Of those who were tested, 21% had an FGFR mutation but only
42% received erdafitinib'
— Options include specifically testing tumors for FGFR3 alterations
(eg, RT-PCR companion assay) or more comprehensive approaches
(eg, NGS panels, liquid biopsy)
The goal is to offer patients the full range of available therapeutic
options to ensure the best possible outcome
1.Nimgaonkar Net al. JAMA Oncol 2022::1070-1072. PeerView.com
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THOR-2: Oral Erdafitinib Versus
Intravesical Chemotherapy!*
BCG-Unresponsive, High-Risk NMIBC
+ FGFR mutations or fusions
+ Cohort 1: papillary tumor only
+ Cohort 2: with or without papillary tumor
+ Cohort 3: intermediate-risk NMIBC with papillary tumor
Investigato:
+ Primary endpoint Exploratory endpoints
= Cohort 1: RFS -
Cohort 1 =
Time, mo
1. tips Icicalias govstudyiNCTO4172675.
4, Catlo IWF etal ESMO 2023, Abstract LBA102. 5, Catto JWF eta SUO 2023, Poster 123.6. Daneshmand S eta. SUO 2029. Abstract 134,
PeerView.com/XSE827
rca
EST ATARUTTTIT occurred (11, erdaftni; 14, chemotherapy)
0008
Cohort 2: C3D1 = 100%; C6D1 = 75%
Cohort 3: CR = 75%
Patients, %
+ At median follow-up of 13.4 mo, median RFS
was not reached for erdafitinib and was
11.6 mo for chemotherapy
+ Atlinical cutoff, 25 total RFS events had
ECOS
x
TT
mime men soe
CR Rate (n= 18)
2 Steinberg G etal. ASCO GU 2023. Abstract $03. 3. Daneshmand S et al ASCO GU 2023, Abstract 504.
Erdafitinib 6 mg/d
hoice of intravesical
chemotherapy
32 weeks (n= 1)
94.4
‘ORR n= 18)
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Intravesical Chemotherapy!*
BCG-Unresponsive, High-Risk NMIBC
+ FGFR mutations or fusions
+ Cohort 1: papillary tumor only
+ Cohort 2: with or without papillary tumor
+ Cohort 3: intermediate-risk NMIBC with papillary tumor
Investigato:
+ Primary endpoint Exploratory endpoints
= Cohort 1: RFS -
Cohort 1 =
Time, mo
1. tips Icicalias govstudyiNCTO4172675.
4, Catlo IWF etal ESMO 2023, Abstract LBA102. 5, Catto JWF eta SUO 2023, Poster 123.6. Daneshmand S eta. SUO 2029. Abstract 134,
PeerView.com/XSE827
rca
EST ATARUTTTIT occurred (11, erdaftni; 14, chemotherapy)
0008
Cohort 2: C3D1 = 100%; C6D1 = 75%
Cohort 3: CR = 75%
Patients, %
+ At median follow-up of 13.4 mo, median RFS
was not reached for erdafitinib and was
11.6 mo for chemotherapy
+ Atlinical cutoff, 25 total RFS events had
ECOS
x
TT
mime men soe
CR Rate (n= 18)
2 Steinberg G etal. ASCO GU 2023. Abstract $03. 3. Daneshmand S et al ASCO GU 2023, Abstract 504.
Erdafitinib 6 mg/d
hoice of intravesical
chemotherapy
32 weeks (n= 1)
94.4
‘ORR n= 18)
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TAR-210: Phase 1 Study of
Erdafitinib Intravesical Delivery?
Cohort 1 Response is assessed every 3 mo with
+ High-risk NMIBC continued treatment for up to 1 y if
(high-grade Ta/T1, no CI recurrence-free (cohort 1) or CR (cohort 3)
papillary only).
Molecular Eligibility SE Part1 Part 2
Aflexible molecular a and ict Dose Escalation Dose Expansion
eligibility strategy is used ria
to detect FGFR alterations | | MANE complete
{Local or central fresh resection of all Expansion Cohort 1
archival tissue-based Chase POLIO. a TAR-210-B
testing by NGS or PCR Dose level 1° Expansion Cohort 3
oR 5
+ Non-RC patients: cohort 1
Urine cell fee DNA + Intermediate-risk NMIBC, das conned Expansion of both
NGS testi recurrent, history of Pa de Le does lord
ee grade only Ta/T1 disease Y
+ Visible target lesions prior
Primary endpoint: safety BETETE Phase 3 MoonRISe-1 Underway":
(AEs, AE severity, DLT) (chemoablat g TAR-210 vs IV chemotherapy in patients
with intermediate-risk NMIBC with
susceptible FGFR alterations
* cial ett date: August 29,2022 Two dierent eran release ates are being avait Pito
1. ps cinicatrals gov/suäyNCTOS316155. 2. Viaseca A et al. ESMO 2023. LBAJOS. 3. ps /elnicalvals govistudy1NCTOS319820.
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Erdafitinib Intravesical Delivery?
Cohort 1 Response is assessed every 3 mo with
+ High-risk NMIBC continued treatment for up to 1 y if
(high-grade Ta/T1, no CI recurrence-free (cohort 1) or CR (cohort 3)
papillary only).
Molecular Eligibility SE Part1 Part 2
Aflexible molecular a and ict Dose Escalation Dose Expansion
eligibility strategy is used ria
to detect FGFR alterations | | MANE complete
{Local or central fresh resection of all Expansion Cohort 1
archival tissue-based Chase POLIO. a TAR-210-B
testing by NGS or PCR Dose level 1° Expansion Cohort 3
oR 5
+ Non-RC patients: cohort 1
Urine cell fee DNA + Intermediate-risk NMIBC, das conned Expansion of both
NGS testi recurrent, history of Pa de Le does lord
ee grade only Ta/T1 disease Y
+ Visible target lesions prior
Primary endpoint: safety BETETE Phase 3 MoonRISe-1 Underway":
(AEs, AE severity, DLT) (chemoablat g TAR-210 vs IV chemotherapy in patients
with intermediate-risk NMIBC with
susceptible FGFR alterations
* cial ett date: August 29,2022 Two dierent eran release ates are being avait Pito
1. ps cinicatrals gov/suäyNCTOS316155. 2. Viaseca A et al. ESMO 2023. LBAJOS. 3. ps /elnicalvals govistudy1NCTOS319820.
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
TAR-210 Provides Sustained Erdafitinib Release in Urine
Over 90 Days With Very Low Plasma Concentrations’
Urine Concentration Plasma Concentration
a 8
3
|rar-2t0.0] mess
333
Concentration of Erdafitinib,
Mean (SD), ng/mL
500 TAR210-8 - 7
Plasma Concentration ("=") T TaR2108
87 1 8 18 2 43 57
‘Treatment Day (Cycle 1) ‘Treatment Day (Cycle 1)
+ Steady-state mean plasma concentrations are >50x lower than oral erdafitinib 9 mg daily
+ No hyperphosphatemia was observed
1. Viaseca À et al ESMO 2023, Abstract LEA 104. PeerView.com
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Over 90 Days With Very Low Plasma Concentrations’
Urine Concentration Plasma Concentration
a 8
3
|rar-2t0.0] mess
333
Concentration of Erdafitinib,
Mean (SD), ng/mL
500 TAR210-8 - 7
Plasma Concentration ("=") T TaR2108
87 1 8 18 2 43 57
‘Treatment Day (Cycle 1) ‘Treatment Day (Cycle 1)
+ Steady-state mean plasma concentrations are >50x lower than oral erdafitinib 9 mg daily
+ No hyperphosphatemia was observed
1. Viaseca À et al ESMO 2023, Abstract LEA 104. PeerView.com
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TAR-210 Provided High Rate of Response’
Cohort 1: FGFR-Altered High-Risk NMIBC Cohort 3: FGFR-Altered Intermediate-Risk NMIBC
(N = 16)? (N = 27)?
Recurrence-free rate: 82% CR rate: 87%
M TAR210.0(0=7) TAR 210-.0(0= 13)
= TAR210.8(0=9) = TAR210-8(0= 14)
> Median durationcftreatmentexposure Response Response
with TAR-210-0,43 mo (range, 2.9) © Recurencatre Medan durationcttreatmentexposirewith $e Non-CRNon-PD
Recurrence TAR210.0:3.3 mo (range, 0-10)
Treatmentengoing
Treatment 2 remrecicrccto,
> Treatment
ee aisconinuaton
Treatment completed 1 Treatrent completes
Median duratonofteatmentexposure = Follow-upperod = Folowup period
[Median duration of treatment exposure with
TAR210.8:4.2 mo (range, 1-12)
180 zu 180 270 260
Treatment Duration, Treatment Duration, d
Patent characteris (N = 16) median age 73.5 y (range, 62:00) 75% were male; 75% and 25% ha tumor stage Ta and Tt, respective, 44% had multiple
tumors; 100% had prior BCG. * Patent chaacterstes (N = 27) median age, 67 y (range, 41-87): 85% were mae; 100% had tumor stage Ta; 41% had mulipe tumors
22% had prior BCG, 59% had prior intravesical chemotherapy a
Y Waseca A et al, ESMO 2023. Abstract LBATOS PeerView.com
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Cohort 1: FGFR-Altered High-Risk NMIBC Cohort 3: FGFR-Altered Intermediate-Risk NMIBC
(N = 16)? (N = 27)?
Recurrence-free rate: 82% CR rate: 87%
M TAR210.0(0=7) TAR 210-.0(0= 13)
= TAR210.8(0=9) = TAR210-8(0= 14)
> Median durationcftreatmentexposure Response Response
with TAR-210-0,43 mo (range, 2.9) © Recurencatre Medan durationcttreatmentexposirewith $e Non-CRNon-PD
Recurrence TAR210.0:3.3 mo (range, 0-10)
Treatmentengoing
Treatment 2 remrecicrccto,
> Treatment
ee aisconinuaton
Treatment completed 1 Treatrent completes
Median duratonofteatmentexposure = Follow-upperod = Folowup period
[Median duration of treatment exposure with
TAR210.8:4.2 mo (range, 1-12)
180 zu 180 270 260
Treatment Duration, Treatment Duration, d
Patent characteris (N = 16) median age 73.5 y (range, 62:00) 75% were male; 75% and 25% ha tumor stage Ta and Tt, respective, 44% had multiple
tumors; 100% had prior BCG. * Patent chaacterstes (N = 27) median age, 67 y (range, 41-87): 85% were mae; 100% had tumor stage Ta; 41% had mulipe tumors
22% had prior BCG, 59% had prior intravesical chemotherapy a
Y Waseca A et al, ESMO 2023. Abstract LBATOS PeerView.com
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Safety of TAR-210 Treatment in Patients
With High-Risk NMIBC*
Cohort 1 Cohort 3
High-Risk NMIBC Intermediate-Risk NMIBC | All patients
Patients With Events, n (%) E
TAR-210-B | TAR-210-D | TAR-210-B | TAR-210-D (N= 43)
(n=9) (n=7) ( 4) (n=13)
21 AE 9 (100) 6 (85.7) 13 (92.9) 7 (53.8) 35 (81.4)
21 TRAE? 6 (66.7) 2 (28.6) 6 (42.9) 3 (23.1) 17 (39.5)
Hematuria 3 (33.3) 1 (14.3) 5 (85.7) 1(7.7) 10 (23.3)
Dysuria 3 (33.3) 1 (14.3) 3(21.4) 1(77) 8 (18.6)
Micturition urgency 141.1) 0 3 (21.4) o 403)
Urinary tract infection 0 0 2(14.3) 1(77) 3(7)
TRAE? grade 22 2 (22.2) 0 4 (28.6) 1(77) 7 (163)
ste are treatment related AES by preferred term that were reported in >1 patient in eter cohort en
1.Viaseca A et al ESMO 2023 LBATOS. PeerView.com
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With High-Risk NMIBC*
Cohort 1 Cohort 3
High-Risk NMIBC Intermediate-Risk NMIBC | All patients
Patients With Events, n (%) E
TAR-210-B | TAR-210-D | TAR-210-B | TAR-210-D (N= 43)
(n=9) (n=7) ( 4) (n=13)
21 AE 9 (100) 6 (85.7) 13 (92.9) 7 (53.8) 35 (81.4)
21 TRAE? 6 (66.7) 2 (28.6) 6 (42.9) 3 (23.1) 17 (39.5)
Hematuria 3 (33.3) 1 (14.3) 5 (85.7) 1(7.7) 10 (23.3)
Dysuria 3 (33.3) 1 (14.3) 3(21.4) 1(77) 8 (18.6)
Micturition urgency 141.1) 0 3 (21.4) o 403)
Urinary tract infection 0 0 2(14.3) 1(77) 3(7)
TRAE? grade 22 2 (22.2) 0 4 (28.6) 1(77) 7 (163)
ste are treatment related AES by preferred term that were reported in >1 patient in eter cohort en
1.Viaseca A et al ESMO 2023 LBATOS. PeerView.com
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Bladder Preservation Approaches for MIBC
Phase 3 SunRISe-2: TAR-200 + PD-1 Inhibitor Cetrelimab vs Concurrent Chemoradiotherapy!?
Key Eligibility Criteria
Patients with MIBC
Cetrelimab + TAR-200
Q3W (indwelling) for first 18 wk; then
: HEAR No, me starting on week 24, Q12W through Assessments until
lot receiving study year 3 histologically proven presence
Stratification? of MIBC, clinical evidence of
nodal or metastatic disease
(per RECIST v1.1), radical
cystectomy, death, or end of
study, whichever occurs first
Completeness (visibly
complete vs incomplete
[residual tumor <3])
Tumor stage (t0 vs
Ta/T1/Tis vs T2-T4a)
N=~550
Cisplatin 35 mg/m
gemcitabine 27 Im? Q2W x 6 wk
investigator's choice) +
radiation therapy?
+ Primary endpoint: bladder-intact EFS
* investigator's choice of conventional radiotherapy over 8.5 weeks of hypotactionated radiotherapy over 4 weeks. ® Based on screening re-TURBT. i”
1. ps enicatriats govstudyINCTOS6SE862. 2 Willams SO etal ASCO 2021. Abstract TPSASEO. PeerView.com
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Phase 3 SunRISe-2: TAR-200 + PD-1 Inhibitor Cetrelimab vs Concurrent Chemoradiotherapy!?
Key Eligibility Criteria
Patients with MIBC
Cetrelimab + TAR-200
Q3W (indwelling) for first 18 wk; then
: HEAR No, me starting on week 24, Q12W through Assessments until
lot receiving study year 3 histologically proven presence
Stratification? of MIBC, clinical evidence of
nodal or metastatic disease
(per RECIST v1.1), radical
cystectomy, death, or end of
study, whichever occurs first
Completeness (visibly
complete vs incomplete
[residual tumor <3])
Tumor stage (t0 vs
Ta/T1/Tis vs T2-T4a)
N=~550
Cisplatin 35 mg/m
gemcitabine 27 Im? Q2W x 6 wk
investigator's choice) +
radiation therapy?
+ Primary endpoint: bladder-intact EFS
* investigator's choice of conventional radiotherapy over 8.5 weeks of hypotactionated radiotherapy over 4 weeks. ® Based on screening re-TURBT. i”
1. ps enicatriats govstudyINCTOS6SE862. 2 Willams SO etal ASCO 2021. Abstract TPSASEO. PeerView.com
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Harnessing IO for Trimodality Therapy in MIBC:
Phase 3 KEYNOTE-992
Pembrolizumab + Chemoradiotherapy Versus Chemoradiotherapy Alone!
Pembrolizumab Cystoscopy,
Key Eligibility
iteri 400 mg IV Q6W urine cytology,
ne Cystoscopy, urine Ba biopsy as
(T2-T4 NOMO) cytology, biopsy of indicated, and
+ Opting for tumor bed, and imaging Q12W
bladder imaging 10 wk (+ 2 wk)
preservation Placebo | (#2 wk) after CRT through year 2
(N = 636) SAN Q24W (+ 2 wk)
(0319) beyond 2 y
Stratification
- ECOG PS (0 or 1 vs 2)
= PD-L1 CPS (<10 vs 210)
— T stage (T2 vs T 3/4)
- Geographic region (US vs Europe vs ROW)
Primary endpoint: Bladder-intact EFS
1. Tissot G et al Eur Ur! Focus. 2023:9:27-228 PeerView.com
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Phase 3 KEYNOTE-992
Pembrolizumab + Chemoradiotherapy Versus Chemoradiotherapy Alone!
Pembrolizumab Cystoscopy,
Key Eligibility
iteri 400 mg IV Q6W urine cytology,
ne Cystoscopy, urine Ba biopsy as
(T2-T4 NOMO) cytology, biopsy of indicated, and
+ Opting for tumor bed, and imaging Q12W
bladder imaging 10 wk (+ 2 wk)
preservation Placebo | (#2 wk) after CRT through year 2
(N = 636) SAN Q24W (+ 2 wk)
(0319) beyond 2 y
Stratification
- ECOG PS (0 or 1 vs 2)
= PD-L1 CPS (<10 vs 210)
— T stage (T2 vs T 3/4)
- Geographic region (US vs Europe vs ROW)
Primary endpoint: Bladder-intact EFS
1. Tissot G et al Eur Ur! Focus. 2023:9:27-228 PeerView.com
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TURBT + Chemo-Immunotherapy Alone for MIBC
HCRN GU16-2571$ bili
ey EOS Criteria TE
+ ¢T2-4aNOMO (95% Cl, 32%-55%)
N=76
+ nivolumab x 4 cycles
Clinical restaging: cystoscopy + biopsies, urine cytology, MRI
n=72
clinical
Outcomes of Patients
With Clinical CR
Time From Registration, mo
m Cystectomy free
Co-primary endpoints: cCR rate and performance of M Local recurrence
ESAS CCR in predicting treatment benefit (ie, 2-y MFS if no © Cystectomy
cystectomy and pCR in immediate cystectomy) Bi Metssiniiarecızrenge,
Treatment based on patients’ choice. exons né
1. Galsky MD et al. ASCO 2021. Abstract 4503, 2. Galsky MD et al. ASCO GU 2023. Abstract 447. 3. Galsky MD et al Nat Med, 2023:29:2825-2634, PeerView.com
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HCRN GU16-2571$ bili
ey EOS Criteria TE
+ ¢T2-4aNOMO (95% Cl, 32%-55%)
N=76
+ nivolumab x 4 cycles
Clinical restaging: cystoscopy + biopsies, urine cytology, MRI
n=72
clinical
Outcomes of Patients
With Clinical CR
Time From Registration, mo
m Cystectomy free
Co-primary endpoints: cCR rate and performance of M Local recurrence
ESAS CCR in predicting treatment benefit (ie, 2-y MFS if no © Cystectomy
cystectomy and pCR in immediate cystectomy) Bi Metssiniiarecızrenge,
Treatment based on patients’ choice. exons né
1. Galsky MD et al. ASCO 2021. Abstract 4503, 2. Galsky MD et al. ASCO GU 2023. Abstract 447. 3. Galsky MD et al Nat Med, 2023:29:2825-2634, PeerView.com
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FAN
PeerView.com/XSE827
Linda: A Patient With NMIBC
(Gr)
What options will Linda
68-year-old patient with NMIBC have for therapy now and
in the future?
ECOG PS 1
Papillary disease + Systemic immune checkpoint
BCG-unresponsive blockade with pembrolizumab
Undergoes repeat TURBT; + Gemcitabine/docetaxel
no residual tumor sequential treatment
+ Nadofaragene firadenovec gene
therapy once every 3 months
+ TAR-200 approach in the future
PeerView.com
Copyright © 2000-2024, PeerView
PeerView.com/XSE827
Linda: A Patient With NMIBC
(Gr)
What options will Linda
68-year-old patient with NMIBC have for therapy now and
in the future?
ECOG PS 1
Papillary disease + Systemic immune checkpoint
BCG-unresponsive blockade with pembrolizumab
Undergoes repeat TURBT; + Gemcitabine/docetaxel
no residual tumor sequential treatment
+ Nadofaragene firadenovec gene
therapy once every 3 months
+ TAR-200 approach in the future
PeerView.com
Copyright © 2000-2024, PeerView
Several Ongoing Phase 3 Trials With
Perioperative Immunotherapy
Cisplatin-Eligible Trials
CA017-078*
Cisplatin Eligible
Neoadjuvant phase Adjuvant phase
+ Gemícis + nivolumab
+ Fully accrued N = 861
NIAGARA?
+ Gem/cis + durvalumab
+ Fully accrued N = 1,063
KEYNOTE-866°
+ Gem/cis + pembrolizumab
+ Fully accrued 907
KEYNOTE-B15/EV-304*
Radical cystectomy and + Pembrolizumab + EV
pelvic lymph node dissection + Enrollment ongoing (estimated N = 784)
10 + chemo
or
10 + novel agent
10 + novel agent
Placebo + chemo Placebo
1. Mts /eiicatials gowstudyINCT03661320, 2. htps:/enicalialsgovistudyINCTO3732677. 3. htps:tincaials gowstudyINCTO3S24856, ea
4: ips Ieiicavats gostudyNCTOS700124, PeerView.com
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Perioperative Immunotherapy
Cisplatin-Eligible Trials
CA017-078*
Cisplatin Eligible
Neoadjuvant phase Adjuvant phase
+ Gemícis + nivolumab
+ Fully accrued N = 861
NIAGARA?
+ Gem/cis + durvalumab
+ Fully accrued N = 1,063
KEYNOTE-866°
+ Gem/cis + pembrolizumab
+ Fully accrued 907
KEYNOTE-B15/EV-304*
Radical cystectomy and + Pembrolizumab + EV
pelvic lymph node dissection + Enrollment ongoing (estimated N = 784)
10 + chemo
or
10 + novel agent
10 + novel agent
Placebo + chemo Placebo
1. Mts /eiicatials gowstudyINCT03661320, 2. htps:/enicalialsgovistudyINCTO3732677. 3. htps:tincaials gowstudyINCTO3S24856, ea
4: ips Ieiicavats gostudyNCTOS700124, PeerView.com
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PeerView.com/XSE827
Several Ongoing Phase 3 Trials With
Perioperative Immunotherapy (Cont'd)
Cisplatin Ineligible Cisplatin-Ineligible Trials
Neoadjuvant phase Adjuvant phase KEYNOTE-905/EV-3031
+ Pembrolizumab + EV
+ Enrollment ongoing (estimated N = 857)
VOLGA?3
lo+ 10+ + Durvalumab + tremelimumab + EV
novel agent novel agent + Enrollment ongoing (estimated N = 830)
SunRISe-44° (phase 2)
+ TAR-200 + cetrelimab
+ Enrollment ongoing (estimated N = 160)
Observation
Radical cystectomy and
pelvic lymph node dissection
1. tps hu icli. govstudyINCTO3924895. 2. htps-ciniclrals-goustucyiNCTO4960700. 3, Pontes T tal. ASCO GU 2022. Abstract TPSS79 Penn
4 ips Ichicaltnal govstodyNNCTOADI9512, 5, Pautka SP etal. ASCO GU 2023. Abaract TPSS84. PeerView.com
Copyright © 2000-2024, PeerView
Several Ongoing Phase 3 Trials With
Perioperative Immunotherapy (Cont'd)
Cisplatin Ineligible Cisplatin-Ineligible Trials
Neoadjuvant phase Adjuvant phase KEYNOTE-905/EV-3031
+ Pembrolizumab + EV
+ Enrollment ongoing (estimated N = 857)
VOLGA?3
lo+ 10+ + Durvalumab + tremelimumab + EV
novel agent novel agent + Enrollment ongoing (estimated N = 830)
SunRISe-44° (phase 2)
+ TAR-200 + cetrelimab
+ Enrollment ongoing (estimated N = 160)
Observation
Radical cystectomy and
pelvic lymph node dissection
1. tps hu icli. govstudyINCTO3924895. 2. htps-ciniclrals-goustucyiNCTO4960700. 3, Pontes T tal. ASCO GU 2022. Abstract TPSS79 Penn
4 ips Ichicaltnal govstodyNNCTOADI9512, 5, Pautka SP etal. ASCO GU 2023. Abaract TPSS84. PeerView.com
Copyright © 2000-2024, PeerView
Adjuvant MIBC Trials With PD-L1/PD-1 Inhibitors
IMvigor0101
Atezolizumab
Observation
+ Primary endpoint: DFS
+ Key secondary
endpoints: OS, DSS,
CheckMate -274?
Nivolumab
Primary endpoint: DFS
Key secondary
AMBASSADOR?
Coprimary endpoints:
DFS and OS
Key secondary
nite: endpoints: OS and DFS
distant MFS, NUTRFS ee y in PD-L1-positive and
Z PD-L1-negative patients
Did not meet DFS Met DFS Met DFS
primary endpoint primary endpoint primary endpoint
1. ips Ielnicalrias govstudyiNCTO2450331. 2. tpsIeiicatials govstudyINCTO2632408. 3. ntpsIciicatíls govstudyINCTO3244384,
PeerView.com/XSE827
FDA approved August 2021
PeerView.com
Copyright © 2000-2024, PeerView
IMvigor0101
Atezolizumab
Observation
+ Primary endpoint: DFS
+ Key secondary
endpoints: OS, DSS,
CheckMate -274?
Nivolumab
Primary endpoint: DFS
Key secondary
AMBASSADOR?
Coprimary endpoints:
DFS and OS
Key secondary
nite: endpoints: OS and DFS
distant MFS, NUTRFS ee y in PD-L1-positive and
Z PD-L1-negative patients
Did not meet DFS Met DFS Met DFS
primary endpoint primary endpoint primary endpoint
1. ips Ielnicalrias govstudyiNCTO2450331. 2. tpsIeiicatials govstudyINCTO2632408. 3. ntpsIciicatíls govstudyINCTO3244384,
PeerView.com/XSE827
FDA approved August 2021
PeerView.com
Copyright © 2000-2024, PeerView
CheckMate -274: Continued DFS Benefit Was Observed With
Nivolumab Versus Placebo in Both Populations’
NT 5 PD-L1 21%
100:
Madian DFS 95% CI, mo
so Median DFS (95% C0, mo so:
O. A wo FEBRES ENE
° = mee * ¿n=
HR =052(95% 0,037.07
n HR=071 05% 0, 058-086) 10 Te)
569%
20 CO Pr Nivolumab
g 50: Nivolumab E so:
40 so
30 pon ES
20 ¿ Placebo he
10 H Kt
ot + ot
0 8 de de 24 do 36 de de à © & 0 512 de À do 30 & de 54 © 0
Months Months
oat isk No. at ioe
hyo 38 25 a m 10 wn mB 7 4 4 0 wur 8 mon & os 2m a 2 0
AE mow sosa
mDFS doubled with nivolumab vs placebo | _[_ mDFS was >6x longer with nivolumab vs placebo
Media folow-up of 38.1 months: minimum folow-up of 31.8 months 7
1 "Caley MO et a ASCO GU 2029 Aeac SAGAS, PeerView.com
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
Nivolumab Versus Placebo in Both Populations’
NT 5 PD-L1 21%
100:
Madian DFS 95% CI, mo
so Median DFS (95% C0, mo so:
O. A wo FEBRES ENE
° = mee * ¿n=
HR =052(95% 0,037.07
n HR=071 05% 0, 058-086) 10 Te)
569%
20 CO Pr Nivolumab
g 50: Nivolumab E so:
40 so
30 pon ES
20 ¿ Placebo he
10 H Kt
ot + ot
0 8 de de 24 do 36 de de à © & 0 512 de À do 30 & de 54 © 0
Months Months
oat isk No. at ioe
hyo 38 25 a m 10 wn mB 7 4 4 0 wur 8 mon & os 2m a 2 0
AE mow sosa
mDFS doubled with nivolumab vs placebo | _[_ mDFS was >6x longer with nivolumab vs placebo
Media folow-up of 38.1 months: minimum folow-up of 31.8 months 7
1 "Caley MO et a ASCO GU 2029 Aeac SAGAS, PeerView.com
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
CheckMate -274: Interim OS Data Favored
Nivolumab Versus Placebo in Both Populations’
IT PD-L1 2 1%
100: 100:
20: so
eo oo
70 : mo
Fa i 2 ! |
g5 H 8% H H
40 i Placebo 40 | |
d H Median OS (95% Ci), mo i H Median OS. mo
30 t NVO 169.5 (58.1-NE) au : Se NR (NE)
20 H | pao 501 G82NE) 20 ! | P80 NRGSONE)
H ¡ "hr ox ch. 076 rase) i {HR (95% cn, 056 020000)
10 H H 10- H H
o: - - - - - - o - + -
06 2m 30 36 d2 de Sa do de 72 78 0 8 Ro À do Em a
No. at risk rie No. at risk Months;
NVO 359 326 200 268 244 220 188 150 123 92 60 30 AO NNOMO WT HM 7 MM 1 0
PBO 356 308 281 254 226 194 167 136 109 79 56 32 10 0 PEO 142 116 104 87 65 46 38 26 12 2 0
25 folowup is ongoing a the prespecified statistical boundary for significance was not met atte me ofthese analyses. Median (minimum) olowup inthe ITT
‘population, 36.1 (31.6) months; median (minimum) flow in PO-L1 21% populaben, 23.8 (114) months. OS was dened as ème tom date of randomzatn 1 date of
‘eat (rom any cause)
1. Galsky MD et al. EAU 2024. PeerView.com
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
Nivolumab Versus Placebo in Both Populations’
IT PD-L1 2 1%
100: 100:
20: so
eo oo
70 : mo
Fa i 2 ! |
g5 H 8% H H
40 i Placebo 40 | |
d H Median OS (95% Ci), mo i H Median OS. mo
30 t NVO 169.5 (58.1-NE) au : Se NR (NE)
20 H | pao 501 G82NE) 20 ! | P80 NRGSONE)
H ¡ "hr ox ch. 076 rase) i {HR (95% cn, 056 020000)
10 H H 10- H H
o: - - - - - - o - + -
06 2m 30 36 d2 de Sa do de 72 78 0 8 Ro À do Em a
No. at risk rie No. at risk Months;
NVO 359 326 200 268 244 220 188 150 123 92 60 30 AO NNOMO WT HM 7 MM 1 0
PBO 356 308 281 254 226 194 167 136 109 79 56 32 10 0 PEO 142 116 104 87 65 46 38 26 12 2 0
25 folowup is ongoing a the prespecified statistical boundary for significance was not met atte me ofthese analyses. Median (minimum) olowup inthe ITT
‘population, 36.1 (31.6) months; median (minimum) flow in PO-L1 21% populaben, 23.8 (114) months. OS was dened as ème tom date of randomzatn 1 date of
‘eat (rom any cause)
1. Galsky MD et al. EAU 2024. PeerView.com
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
AMBASSADOR: Pembrolizumab Demonstrated
DFS Benefit at Interim Analysis!
DFS (ITT Population)
No. of Events/Total Median (95% CI), mo
je Pembrotzunab 175% EI
2 observation 172048 1097202)
» HR = 0.69 (66% C1,0540.87),P=.001
ae
g « Pembrolizumab
‘Median follow-up (range)
22.3 months (0.03-48.9)
08,%
Overall Survival
No. ofEvents/Total _ Median (95% Cl), mo
1317884 50.9 (43.8-NR)
126848 55.8 (53.3-NR)
HR = 0.98 (95% CI, 0.76-1.26); P< 884
Pembroizumab
‘Observation
Pembrolizumab
Median follow-up (range)
36.9 months (36.9-37.9)
1. Apolo AB et al ASCO GU 2024. LBAS31.
PeerView.com/XSE827
Time, mo
PeerView.com
Copyright © 2000-2024, PeerView
DFS Benefit at Interim Analysis!
DFS (ITT Population)
No. of Events/Total Median (95% CI), mo
je Pembrotzunab 175% EI
2 observation 172048 1097202)
» HR = 0.69 (66% C1,0540.87),P=.001
ae
g « Pembrolizumab
‘Median follow-up (range)
22.3 months (0.03-48.9)
08,%
Overall Survival
No. ofEvents/Total _ Median (95% Cl), mo
1317884 50.9 (43.8-NR)
126848 55.8 (53.3-NR)
HR = 0.98 (95% CI, 0.76-1.26); P< 884
Pembroizumab
‘Observation
Pembrolizumab
Median follow-up (range)
36.9 months (36.9-37.9)
1. Apolo AB et al ASCO GU 2024. LBAS31.
PeerView.com/XSE827
Time, mo
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Copyright © 2000-2024, PeerView
Potential for Improving Daily Management:
Subcutaneous 10
Phase 3 Studies
IMscin00112
+ SC atezolizumab in NSCLC
+ January 2024: approved in the European Union
for all indications?
+ SC administration provides an
alternative with potential benefits for
both patients and providers
CheckMate -67T*
SC dosing may: Under FDA Reviews
- Alleviate the need for IV vein ports e en Be DE een:
= i i . : similar ORR, DCR, ant
eg ora Share in SE val SC sein ie «5 ra
— Reduce dose preparation and CREST”
administration times + Cohort B: SC sasanlimab in NMIBC
— Optimize occupancy in infusion RELATIVITY-1278
centers + SC nivolumab + relatlimab (LAG-3) in 1L metastatic
melanoma
1. Buroto Metal Ann Oncol 2023:34:093702. 2. Ntpsienicatias govstusy/NCTO3735121. 3 htpsirtwordpharma comstary/5818570,
4. tps lnicaliials govistudyINCTO4810078. 5. George S et al. ASCO GU 2024. LBA3E0.6.hitps:finance yahoo.comMnewsiwfood-drug-administraton-accepts- y 7,
105000988 himl. 7. ps Icincahals govistudyINCTO$ 165317. 8. ps lcinicatials gowstudyINCTOS625300. PeerView.com
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
Subcutaneous 10
Phase 3 Studies
IMscin00112
+ SC atezolizumab in NSCLC
+ January 2024: approved in the European Union
for all indications?
+ SC administration provides an
alternative with potential benefits for
both patients and providers
CheckMate -67T*
SC dosing may: Under FDA Reviews
- Alleviate the need for IV vein ports e en Be DE een:
= i i . : similar ORR, DCR, ant
eg ora Share in SE val SC sein ie «5 ra
— Reduce dose preparation and CREST”
administration times + Cohort B: SC sasanlimab in NMIBC
— Optimize occupancy in infusion RELATIVITY-1278
centers + SC nivolumab + relatlimab (LAG-3) in 1L metastatic
melanoma
1. Buroto Metal Ann Oncol 2023:34:093702. 2. Ntpsienicatias govstusy/NCTO3735121. 3 htpsirtwordpharma comstary/5818570,
4. tps lnicaliials govistudyINCTO4810078. 5. George S et al. ASCO GU 2024. LBA3E0.6.hitps:finance yahoo.comMnewsiwfood-drug-administraton-accepts- y 7,
105000988 himl. 7. ps Icincahals govistudyINCTO$ 165317. 8. ps lcinicatials gowstudyINCTOS625300. PeerView.com
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
Nivolumab SC Provides Clinical Equipoise to
Standard IV Dosing!
+ Eligibility: Patients with advanced RCC/mRCC with clear cell component who had
progressed during or after receiving <2 prior systemic regimens
+ Co-primary endpoints met: PK noninferiority between NIVO SC and IV
NIVO SC NIVO IV
1,200 mg + rHuPH20 Q4W 3 mg/kg Q2W
(in = 247 in = 245)
Number of doses received 8.6 Art?
Administration time, min 4.7 30.9
Patients with 21 dose delayed, n (%) 89 (36.0) 134 (64.7)
Patients with 21 infusion/injection interrupted,
n (4) 1 (0.4) 10 (4.1)
+ Average administration time with nivolumab SC was <5 minutes
+ Important for patients receiving single agent checkpoint blockade
+ Treatment implications in the perioperative setting
1. George S et al, ASCO GU 2024, LBA 360, PeerView.com
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
Standard IV Dosing!
+ Eligibility: Patients with advanced RCC/mRCC with clear cell component who had
progressed during or after receiving <2 prior systemic regimens
+ Co-primary endpoints met: PK noninferiority between NIVO SC and IV
NIVO SC NIVO IV
1,200 mg + rHuPH20 Q4W 3 mg/kg Q2W
(in = 247 in = 245)
Number of doses received 8.6 Art?
Administration time, min 4.7 30.9
Patients with 21 dose delayed, n (%) 89 (36.0) 134 (64.7)
Patients with 21 infusion/injection interrupted,
n (4) 1 (0.4) 10 (4.1)
+ Average administration time with nivolumab SC was <5 minutes
+ Important for patients receiving single agent checkpoint blockade
+ Treatment implications in the perioperative setting
1. George S et al, ASCO GU 2024, LBA 360, PeerView.com
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
(E) Michelle: A Patient With MIBC
Panel Discussion
+ 56-year-old female athlete, excellent health How do you counsel the patient?
+ Hematuria off and on for 9 mo;
attributes it to “runner's hematuria”
+ Cystoscopy and imaging consistent with
Would adjuvant nivolumab be
appropriate for this patient?
a sessile mass at the anterior bladder wall Do you do ctDNA testing?
+ Diagnosis of clinically localized MIBC
+ Good renal function + BCAN can be helpful for patients with MIBC
un en as they transition to new challenges in their
lo neuropathy or hearing loss day ede ies
+ Treated with 4 cycles of gemcitabine plus ;
cisplatin followed by RC/neobladder + Care teams need to be aware ofirAEs
+ Pathology: T3b, NO (32 LNs removed) associated with immune checkpoint
inhibitors that can affect many organs and
XN have variable timing (eg, Gl symptoms)
PeerView.com
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
Panel Discussion
+ 56-year-old female athlete, excellent health How do you counsel the patient?
+ Hematuria off and on for 9 mo;
attributes it to “runner's hematuria”
+ Cystoscopy and imaging consistent with
Would adjuvant nivolumab be
appropriate for this patient?
a sessile mass at the anterior bladder wall Do you do ctDNA testing?
+ Diagnosis of clinically localized MIBC
+ Good renal function + BCAN can be helpful for patients with MIBC
un en as they transition to new challenges in their
lo neuropathy or hearing loss day ede ies
+ Treated with 4 cycles of gemcitabine plus ;
cisplatin followed by RC/neobladder + Care teams need to be aware ofirAEs
+ Pathology: T3b, NO (32 LNs removed) associated with immune checkpoint
inhibitors that can affect many organs and
XN have variable timing (eg, Gl symptoms)
PeerView.com
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
Supporting Effective Team-Based Collaboration
Recent progress in mUC calls for a collaborative approach to care
+ Numerous advances in therapeutic management of mUC have occurred
over the last few years
Translating these findings into real-world clinical practice requires careful
planning, discussion, and coordination among cancer care teams
Establish dependable relationships with other specialties
and disciplines (eg, urology, radiation oncology, pathology,
oncology pharmacy)
Build solid relationships across disciplines to optimize patient
experiences and outcomes with a variety of therapeutic agents
PeerView.com
Copyrigh
Recent progress in mUC calls for a collaborative approach to care
+ Numerous advances in therapeutic management of mUC have occurred
over the last few years
Translating these findings into real-world clinical practice requires careful
planning, discussion, and coordination among cancer care teams
Establish dependable relationships with other specialties
and disciplines (eg, urology, radiation oncology, pathology,
oncology pharmacy)
Build solid relationships across disciplines to optimize patient
experiences and outcomes with a variety of therapeutic agents
PeerView.com
Copyrigh
Is Cisplatin (Versus Carboplatin) a Better Partner for
Immune Checkpoint Inhibition?
, IMvigor13012 YNOTE-361?
Investigator's
Choice of ArmA Arm C
Chemo Patients, n mPFS,mo mPFS,mo HR (95% Cl)
(n=451) (n=400)
Events/
Participants CES)
Cisplatin 273 88 64 0.73(055-0.97) | 2071312 0.67 (0.51-0.89)
63 0.84(0.70-1.02) 0.86 (0.68-1.09)
{Sly MO el Lancet 2020386 547.1557. 2 Caty MO eal. Cl ep Med 202 10103 nine ahead ot pt] —
3. Pontes Teta Lancet Oncol, 2021:22:931-945. PeerView.com
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
Immune Checkpoint Inhibition?
, IMvigor13012 YNOTE-361?
Investigator's
Choice of ArmA Arm C
Chemo Patients, n mPFS,mo mPFS,mo HR (95% Cl)
(n=451) (n=400)
Events/
Participants CES)
Cisplatin 273 88 64 0.73(055-0.97) | 2071312 0.67 (0.51-0.89)
63 0.84(0.70-1.02) 0.86 (0.68-1.09)
{Sly MO el Lancet 2020386 547.1557. 2 Caty MO eal. Cl ep Med 202 10103 nine ahead ot pt] —
3. Pontes Teta Lancet Oncol, 2021:22:931-945. PeerView.com
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
Phase 3 CheckMate -901: Nivolumab Plus Gem/Cis
Versus Gem/Cis in Cisplatin-Eligible Patients’?
Key Eligibility Criteria
+ Agez18 y
+ Previously untreated
unresectable
‘or mUC involving the
renal pelvis, ureter,
bladder, or urethra
+ Cisplatin eligible
+ ECOG PS 0-1
Stratification
+ Tumor PD-L1
expression
(2 1% vs < 1%)
+ Liver metastases
(yes vs no)
+ Primary endpoints: OS, PFS per BICR
+ Key secondary endpoints: OS and PFS by PD-L1 2 1%, HRQOL
+ Key exploratory endpoints: ORR per BICR, safety
Combination phase
NIVO 360 mg ond 1 +
Gem 1,000 mg/m? on d 1/d 8 +
Cis 70 mg/m? on d 1 Q3W
Monotherapy phase
NIVO 480 mg Q4W
(until progression,
unacceptable toxicity,
withdrawal, or
up to 24 mo*)
» Median (range) study folow-up, 33.6 (74.624) mo, Patents who daconinued eis could be svtched to gemvcis forthe remainder ofthe platinum doublet cycles
{up 8 in total) < À maximum of 24 mo from fst dose of NIVO administered as part ofthe NIVO + gemveis combination
1. nps/esnicalviaisgow'study/NCTO3036008. 2. van der Heiden MS eta ESMO 2023. Abstract LBAT. 3. van der Helden MS et al. N Engl J Med.
2023:389-1778-1789,
PeerView.com/XSE827
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Versus Gem/Cis in Cisplatin-Eligible Patients’?
Key Eligibility Criteria
+ Agez18 y
+ Previously untreated
unresectable
‘or mUC involving the
renal pelvis, ureter,
bladder, or urethra
+ Cisplatin eligible
+ ECOG PS 0-1
Stratification
+ Tumor PD-L1
expression
(2 1% vs < 1%)
+ Liver metastases
(yes vs no)
+ Primary endpoints: OS, PFS per BICR
+ Key secondary endpoints: OS and PFS by PD-L1 2 1%, HRQOL
+ Key exploratory endpoints: ORR per BICR, safety
Combination phase
NIVO 360 mg ond 1 +
Gem 1,000 mg/m? on d 1/d 8 +
Cis 70 mg/m? on d 1 Q3W
Monotherapy phase
NIVO 480 mg Q4W
(until progression,
unacceptable toxicity,
withdrawal, or
up to 24 mo*)
» Median (range) study folow-up, 33.6 (74.624) mo, Patents who daconinued eis could be svtched to gemvcis forthe remainder ofthe platinum doublet cycles
{up 8 in total) < À maximum of 24 mo from fst dose of NIVO administered as part ofthe NIVO + gemveis combination
1. nps/esnicalviaisgow'study/NCTO3036008. 2. van der Heiden MS eta ESMO 2023. Abstract LBAT. 3. van der Helden MS et al. N Engl J Med.
2023:389-1778-1789,
PeerView.com/XSE827
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Copyright © 2000-2024, PeerView
CheckMate -901: Nivolumab Plus Gem/Cis
Improved OS (Primary Endpoint)'22
12-mo rate:
70.2%
24-mo rate:
x © mo rate:
y © 46.9%
© 40
mos NIVO + gemícis
Treatment Events/Patients (95% Cl), moe is the first 1L
NIVO + gemiois 172/304 21.7 (18.6-26.4) concurrent immune
Gemvcis 193/304 18.9 (14.7-22.4) checkpoint inhibitor
HR = 0.78 (95% CI, 0.63-0.96) + chemotherapy
P=.0171
combination to
improve OS
in this setting
NIVO + gemícis
Gemicis
30
Time, mo
FDA Approved for 1L.
36 42 48 54 60 66
Treatment of
Unresectable or mUC:
‘Median (range) study follow-up, 33.6 (74624) mo. * OS was estimated in al randomized paints and defined as time from randomization to death rom any cause.
For patents without documented death, OS was censored on the last date the patent was known fo be ave. For randomized patients with no folow-up, OS was
‘censored a andomzaton OS final analysis statatcal boundaries: Pvalue boundar
1 van der Heiden MS eta ESMO 2023, Abstract LBAT. 2 van der Hejden MS et al. N Engl J Med. 2023:388:1778-1780 3. hp fa govidrugsiresources-
information approved-drugstéa-approves nivolumat combination <isplatn and. gemetabne-unvesectable-r metastate-uroiheial
PeerView.com/XSE827
311: cal HR 2 0.7880,
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Copyright © 2000-2024, PeerView
Improved OS (Primary Endpoint)'22
12-mo rate:
70.2%
24-mo rate:
x © mo rate:
y © 46.9%
© 40
mos NIVO + gemícis
Treatment Events/Patients (95% Cl), moe is the first 1L
NIVO + gemiois 172/304 21.7 (18.6-26.4) concurrent immune
Gemvcis 193/304 18.9 (14.7-22.4) checkpoint inhibitor
HR = 0.78 (95% CI, 0.63-0.96) + chemotherapy
P=.0171
combination to
improve OS
in this setting
NIVO + gemícis
Gemicis
30
Time, mo
FDA Approved for 1L.
36 42 48 54 60 66
Treatment of
Unresectable or mUC:
‘Median (range) study follow-up, 33.6 (74624) mo. * OS was estimated in al randomized paints and defined as time from randomization to death rom any cause.
For patents without documented death, OS was censored on the last date the patent was known fo be ave. For randomized patients with no folow-up, OS was
‘censored a andomzaton OS final analysis statatcal boundaries: Pvalue boundar
1 van der Heiden MS eta ESMO 2023, Abstract LBAT. 2 van der Hejden MS et al. N Engl J Med. 2023:388:1778-1780 3. hp fa govidrugsiresources-
information approved-drugstéa-approves nivolumat combination <isplatn and. gemetabne-unvesectable-r metastate-uroiheial
PeerView.com/XSE827
311: cal HR 2 0.7880,
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Phase 3 CheckMate -901: Nivolumab Plus Gem/Cis
Improved PFS (Primary Endpoint)'2:2
er ‚Treatment Events/Patients (05% mere NIVO + gem/cis demonstrated
NIVO + gemicis 2111304 7.9(7.6-9.5) statistically significant and
30 Gemicis 191/304 7.6 (6.1-78) clinically meaningful
70: HR = 0.72 (85% CI, 0.59-0.88) improvements in PFS vs
æ 60 P=.0012 gem/cis alone as 1L treatment
ui 50 . for unresectable or mUC
Edo 12-mo rate:
NIVO + gemicis
0 6 12 18 24 30 36 42 4 54 60
Time, mo
Mecian (ange) study folow-up, 33.5 (7.482 4) mo. PFS was estimated in al randomized patents and defined as time rom randomization 1 frst documented
disease progression (per BICR assessment using RECIST VI.1) or death due to any cause, whichever occurred fst. Patents who di nat progress orde were
‘censored at last evaluable tumor assessment Patents without on-study tumor assessments who de nt de were censored at randomizaton, Patients who started any
subsequent anticancer therapy whut pr reported progression were censored at lat evaluable tumor assessment before ination of subsequent therapy. < PFS
foal analysis statistical boundaries: Pave boundary = 01; cial HR = 0.7734, a
‘van der Heiden MS et al. ESMO 2023, Abstract LBAT. 2. van der Hien MS eta. Eng! J Med. 2023:380:1778-1789, PeerView.com
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
Improved PFS (Primary Endpoint)'2:2
er ‚Treatment Events/Patients (05% mere NIVO + gem/cis demonstrated
NIVO + gemicis 2111304 7.9(7.6-9.5) statistically significant and
30 Gemicis 191/304 7.6 (6.1-78) clinically meaningful
70: HR = 0.72 (85% CI, 0.59-0.88) improvements in PFS vs
æ 60 P=.0012 gem/cis alone as 1L treatment
ui 50 . for unresectable or mUC
Edo 12-mo rate:
NIVO + gemicis
0 6 12 18 24 30 36 42 4 54 60
Time, mo
Mecian (ange) study folow-up, 33.5 (7.482 4) mo. PFS was estimated in al randomized patents and defined as time rom randomization 1 frst documented
disease progression (per BICR assessment using RECIST VI.1) or death due to any cause, whichever occurred fst. Patents who di nat progress orde were
‘censored at last evaluable tumor assessment Patents without on-study tumor assessments who de nt de were censored at randomizaton, Patients who started any
subsequent anticancer therapy whut pr reported progression were censored at lat evaluable tumor assessment before ination of subsequent therapy. < PFS
foal analysis statistical boundaries: Pave boundary = 01; cial HR = 0.7734, a
‘van der Heiden MS et al. ESMO 2023, Abstract LBAT. 2. van der Hien MS eta. Eng! J Med. 2023:380:1778-1789, PeerView.com
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Phase 3 CheckMate -901: Nivolumab Plus Gem/Cis
Is Associated With Deep and Durable Responses*?
‘ORR (95% CI) and BOR per BICR* TTR and DOR
70 cram NIVO+Gemicis GemiCis
57.5 Any Objective Response: al =
60 N PR (n=175) (n=130)
ai TTR (21-03), mo 21(2023) 212022)
. 50 y
po 21.7 ra) MDOR (95% CI), mo 9576151 736789)
2 30 or (n= 66) (n=36)
&
20 mTTCR (Q1-03), mo 211922) 21922)
> 313
10
o
FERN 253 283 + ORR and CR rates were notably higher with
NIVO + gem/cis and associated with deep and
PD, % 95 128 durable responses
VE me Pa + The CR rate was nearly doubled with NIVO + gemvcis
À + DOCR was almost 3 times longer with NIVO + gemvcis,
NIVO + Gem/Cis Gem/Cis despite a maximum of 2 y of NIVO treatment
(n= 304) (n = 304)
“in al randomized patents. The most common reasons for UE response Included death before rs tumor assessment, wihérawal a consent. treatment stopped due
to oct, patent never treated, and receip of subsequent anicancer therapy before fist tumor assessment. Based on patients with an objecive response per BICR.
{PR or CR as BOR). * Based on patents with a CR per BIC.
1. van der Heiden MS et al ESMO 2023, Abstract LBAT. 2. van der Helden MS et a. N Engl J Med. 2023:380:1778-1780, ES
3 Senpavde O et al AUA 2024, Abstract POSS. PeerView.com
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Is Associated With Deep and Durable Responses*?
‘ORR (95% CI) and BOR per BICR* TTR and DOR
70 cram NIVO+Gemicis GemiCis
57.5 Any Objective Response: al =
60 N PR (n=175) (n=130)
ai TTR (21-03), mo 21(2023) 212022)
. 50 y
po 21.7 ra) MDOR (95% CI), mo 9576151 736789)
2 30 or (n= 66) (n=36)
&
20 mTTCR (Q1-03), mo 211922) 21922)
> 313
10
o
FERN 253 283 + ORR and CR rates were notably higher with
NIVO + gem/cis and associated with deep and
PD, % 95 128 durable responses
VE me Pa + The CR rate was nearly doubled with NIVO + gemvcis
À + DOCR was almost 3 times longer with NIVO + gemvcis,
NIVO + Gem/Cis Gem/Cis despite a maximum of 2 y of NIVO treatment
(n= 304) (n = 304)
“in al randomized patents. The most common reasons for UE response Included death before rs tumor assessment, wihérawal a consent. treatment stopped due
to oct, patent never treated, and receip of subsequent anicancer therapy before fist tumor assessment. Based on patients with an objecive response per BICR.
{PR or CR as BOR). * Based on patents with a CR per BIC.
1. van der Heiden MS et al ESMO 2023, Abstract LBAT. 2. van der Helden MS et a. N Engl J Med. 2023:380:1778-1780, ES
3 Senpavde O et al AUA 2024, Abstract POSS. PeerView.com
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Treatment-Related AE,
Any
Leading to discontinuation
Phase 3 CheckMate -901:
TRAEs in All Treated Patients’?
NIVO + Gem/Cis (n = 304)
Any Grade
97
21
Gem/Cis (n
Any Grade
93
Decreased platelet count
Decreased white blood cell count
Vomiting
Asthenia
Thrombocytopenia
Pruntus
Constipation
Rash
Diarrhea
Hypothyroidism
Increased blood creatinine
‘Leukopenia
Grade 1-2
El
LES
0
Incidence, %
y
* Includes events that occured in treated patents between frst dose and 30 d after last dose of study therapy. Tomado plot displays individual TRAES occuring at any
‘rade in 210% of treated patients in ether arm. One grade 5 event occurred in each arm (sepais inthe NIVO + gems arm and acute Kidney injury
Inthe gemics arm).
1. van der Heiden MS et al. ESMO 2023, Abstract LBAT. 2. van der Hejden MS et al. N Engl J Med. 2023:389:1778-1789,
PeerView.com/XSE827
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Any
Leading to discontinuation
Phase 3 CheckMate -901:
TRAEs in All Treated Patients’?
NIVO + Gem/Cis (n = 304)
Any Grade
97
21
Gem/Cis (n
Any Grade
93
Decreased platelet count
Decreased white blood cell count
Vomiting
Asthenia
Thrombocytopenia
Pruntus
Constipation
Rash
Diarrhea
Hypothyroidism
Increased blood creatinine
‘Leukopenia
Grade 1-2
El
LES
0
Incidence, %
y
* Includes events that occured in treated patents between frst dose and 30 d after last dose of study therapy. Tomado plot displays individual TRAES occuring at any
‘rade in 210% of treated patients in ether arm. One grade 5 event occurred in each arm (sepais inthe NIVO + gems arm and acute Kidney injury
Inthe gemics arm).
1. van der Heiden MS et al. ESMO 2023, Abstract LBAT. 2. van der Hejden MS et al. N Engl J Med. 2023:389:1778-1789,
PeerView.com/XSE827
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Phase 3 EV-302: Pembrolizumab Plus EV Versus
Gem/Cis in Cisplatin-Eligible Patients’?
Key Eligibility Criteria
+ Previously untreated,
EV + pembrolizumab®
No maximum treatment cycles for
ificati de 5 Treatment until
locally advanced or Suatification EV; maximum 35 cycles for > sion
ae + Cisplatin eligibility pembrolizumab pe
Eligible for platinum, Claber psigtle) ul e progression,
EV, and P 2 PDA expression, unacceptable
PD-L1 inhibitor naive Mones) toxicity, or
en + Liver metastases Chemotherapy completion of
Eo (present/absent) atin o atin maximum cycles
N=886
+ Dual primary endpoints: PFS by BICR and OS
+ Select secondary endpoints: ORR per RECIST v1.1 by BICR
and investigator assessment, safety
* Stasical plan or analysis: the fst panned analysis was performed ater approximately 528 PFS (fna) and 358 OS events (interim): OS was postive at intern,
the OS interim analysis was considered nal. Data cuo August, 2023; FP. Apr 7, 2020; LPI November 9, 2022 * Cispatn ety and assigamentidosing of
patin vs carbopain were protocol defined: patents received 3-uk cycles of EV 1.25 mo/k IV on days 1 and 8 and pembrokzumab 200 mg IV on day 1
*Mtantenance therapy could be used folowing completon andor dsconinuatn of plainum containing era en
1. Podes T etai. Engl Med 2024:390-875-888 PeerView.com
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Gem/Cis in Cisplatin-Eligible Patients’?
Key Eligibility Criteria
+ Previously untreated,
EV + pembrolizumab®
No maximum treatment cycles for
ificati de 5 Treatment until
locally advanced or Suatification EV; maximum 35 cycles for > sion
ae + Cisplatin eligibility pembrolizumab pe
Eligible for platinum, Claber psigtle) ul e progression,
EV, and P 2 PDA expression, unacceptable
PD-L1 inhibitor naive Mones) toxicity, or
en + Liver metastases Chemotherapy completion of
Eo (present/absent) atin o atin maximum cycles
N=886
+ Dual primary endpoints: PFS by BICR and OS
+ Select secondary endpoints: ORR per RECIST v1.1 by BICR
and investigator assessment, safety
* Stasical plan or analysis: the fst panned analysis was performed ater approximately 528 PFS (fna) and 358 OS events (interim): OS was postive at intern,
the OS interim analysis was considered nal. Data cuo August, 2023; FP. Apr 7, 2020; LPI November 9, 2022 * Cispatn ety and assigamentidosing of
patin vs carbopain were protocol defined: patents received 3-uk cycles of EV 1.25 mo/k IV on days 1 and 8 and pembrokzumab 200 mg IV on day 1
*Mtantenance therapy could be used folowing completon andor dsconinuatn of plainum containing era en
1. Podes T etai. Engl Med 2024:390-875-888 PeerView.com
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Phase 3 EV-302: Improved OS With
Enfortumab Vedotin Plus Pembrolizumab'»?
Hi
N Events (0) ER, Two-Sided P-mOS (85% c,mo
100
9 EV+P 442 133(30.1)
047 31.5 (25.4-NR)
(038-058) <00001
80 Chemo 444 226(509) |( 16.1 (13.9-18.3)
70 Risk of death was reduced by
x © 53% in patients who received
& © EV + pembrolizumab
9 4
EV + pembro
30 Chemo
20
ha FDA Full Approval
o for 1L Treatment
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 3% 36 38 of muc2
No. at Risk Time, mo
EV+P 442 426 400 304 76 301 270 222 nn om 12 8 1 1 1 —
Chemo 444 423 303 356 317 263 209 164 125 90 0 37 25 18 12 7 6 2 1 —
* Data euof. August 8, 2023; FP: Api 7, 2020; LPI: November 9, 2022. Median survival folow-up: 17.2 mo. OS at 12 and 18 mo was estimated using Kaplan-Meier
‘method. *Caleted using stratifed Cox proportonal hazards model, HR <1 favors the EV + pembralzumab arm.
Y. Pos T etal N Engl J Med 2024,390.875-888, 2. hips: va da. govidruguresourcesnfoematon-approved:-drugetsa-approves-enforumab-vedotn-gi-
pembrotzumab-lecaly-advanced-ormetastabe-urothelia-cancer PeerView.com
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Enfortumab Vedotin Plus Pembrolizumab'»?
Hi
N Events (0) ER, Two-Sided P-mOS (85% c,mo
100
9 EV+P 442 133(30.1)
047 31.5 (25.4-NR)
(038-058) <00001
80 Chemo 444 226(509) |( 16.1 (13.9-18.3)
70 Risk of death was reduced by
x © 53% in patients who received
& © EV + pembrolizumab
9 4
EV + pembro
30 Chemo
20
ha FDA Full Approval
o for 1L Treatment
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 3% 36 38 of muc2
No. at Risk Time, mo
EV+P 442 426 400 304 76 301 270 222 nn om 12 8 1 1 1 —
Chemo 444 423 303 356 317 263 209 164 125 90 0 37 25 18 12 7 6 2 1 —
* Data euof. August 8, 2023; FP: Api 7, 2020; LPI: November 9, 2022. Median survival folow-up: 17.2 mo. OS at 12 and 18 mo was estimated using Kaplan-Meier
‘method. *Caleted using stratifed Cox proportonal hazards model, HR <1 favors the EV + pembralzumab arm.
Y. Pos T etal N Engl J Med 2024,390.875-888, 2. hips: va da. govidruguresourcesnfoematon-approved:-drugetsa-approves-enforumab-vedotn-gi-
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Phase 3 EV-302: Improved PFS With
Enfortumab Vedotin Plus Pembrolizumab'»?
100 mPFS (95% Cl),
12.5 (104-166)
63 (626.5)
N Events(%) HR®(95% Cl) Two-Sided P
EV+P 442 223(505)
Chemo 444 307(69.1)
045(038054 <00001
388
g 00
wo 50
2 ie
Risk of
a
be EV+pembro | progression or
Sn death was
20 reduced by 55%
a in patients who
E Chemo | received EV +
pembrolizumab
0 2 4 6 8 1 12 14 16 18 20 22 24 2% 28 30 32 34
Time, mo
No, at Risk
EV+P 442 400 381 303 258 204 167 192 102 73 45 33 17 6 3 1 —
Chemo 444 380 27 213 M 78 OS 41 2 1 8 6 $ 3 2 41
Data cto August 8, 2023; FP: Ape 7, 2020; LPI: November 9, 2022. PFS a 12 and 18 mont as estimated using Kaplan-Meier method. Calculated using
strafed Cox proportonal hazards made: HR <1 favors the EV + pembrolzumab am. az
1. Pontes Tet a N Engl Med 2024:300.875-888 PeerView.com
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Enfortumab Vedotin Plus Pembrolizumab'»?
100 mPFS (95% Cl),
12.5 (104-166)
63 (626.5)
N Events(%) HR®(95% Cl) Two-Sided P
EV+P 442 223(505)
Chemo 444 307(69.1)
045(038054 <00001
388
g 00
wo 50
2 ie
Risk of
a
be EV+pembro | progression or
Sn death was
20 reduced by 55%
a in patients who
E Chemo | received EV +
pembrolizumab
0 2 4 6 8 1 12 14 16 18 20 22 24 2% 28 30 32 34
Time, mo
No, at Risk
EV+P 442 400 381 303 258 204 167 192 102 73 45 33 17 6 3 1 —
Chemo 444 380 27 213 M 78 OS 41 2 1 8 6 $ 3 2 41
Data cto August 8, 2023; FP: Ape 7, 2020; LPI: November 9, 2022. PFS a 12 and 18 mont as estimated using Kaplan-Meier method. Calculated using
strafed Cox proportonal hazards made: HR <1 favors the EV + pembrolzumab am. az
1. Pontes Tet a N Engl Med 2024:300.875-888 PeerView.com
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Phase 3 EV-302: Improved Overall Response’
Significant improvement in ORR was
observed with EV + pembrolizumab
si 677 PRE M
= I rum
ie 444
x» 387
g 4
E
5»
* | | |
291
1
o
EV+P ‘Chemotherapy
MDOR (95% Cl) NR (20.2-NR) 7.0 (6.2-10.2)
EV+P
(n= 437)
Confirmed ORR, n (%) 296 (67.7)
(95% Cl) (63.1-72.1)
2-sided P
BOR’, n (%)
CR 127 (29.1)
PR 169 (38.7)
sD 82 (18.8)
PD 38 (8.7)
NE/NAS 21 (4.8)
Chemotherapy
(n = 441)
196 (44.4)
(39.7-49.2)
<.00001
55 (12.5)
141 (32.0)
149 (33.8)
60 (13.6)
36 (8.2)
‘Subgroup analyses: OS benefit with EV + pembrolizumab was consistent with the overall popul
ion, regardless of
cisplatin eligibility or PD-L1 expression status, as well as the presence or absence of liver or visceral metastases?
* Data cutft August 8,2023 ° BOR according to RECIST v1.1 per BICR. CR or PR was confirmed wit repeat scans 228 d afte nal response
“Patents had ether post-baselne assessment and the BOR was determine tobe not evaluable per RECIST v1.1 or no response assessment post baseline
1.Powies T et al N Engl Med 2024;300:875-888, 2 van der Heiden MS et al, ASCO GU 2024. Abstract LBAS30.
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Significant improvement in ORR was
observed with EV + pembrolizumab
si 677 PRE M
= I rum
ie 444
x» 387
g 4
E
5»
* | | |
291
1
o
EV+P ‘Chemotherapy
MDOR (95% Cl) NR (20.2-NR) 7.0 (6.2-10.2)
EV+P
(n= 437)
Confirmed ORR, n (%) 296 (67.7)
(95% Cl) (63.1-72.1)
2-sided P
BOR’, n (%)
CR 127 (29.1)
PR 169 (38.7)
sD 82 (18.8)
PD 38 (8.7)
NE/NAS 21 (4.8)
Chemotherapy
(n = 441)
196 (44.4)
(39.7-49.2)
<.00001
55 (12.5)
141 (32.0)
149 (33.8)
60 (13.6)
36 (8.2)
‘Subgroup analyses: OS benefit with EV + pembrolizumab was consistent with the overall popul
ion, regardless of
cisplatin eligibility or PD-L1 expression status, as well as the presence or absence of liver or visceral metastases?
* Data cutft August 8,2023 ° BOR according to RECIST v1.1 per BICR. CR or PR was confirmed wit repeat scans 228 d afte nal response
“Patents had ether post-baselne assessment and the BOR was determine tobe not evaluable per RECIST v1.1 or no response assessment post baseline
1.Powies T et al N Engl Med 2024;300:875-888, 2 van der Heiden MS et al, ASCO GU 2024. Abstract LBAS30.
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Phase 3 EV-302: TRAEs"?
EV +P (n= 440) Chemo (n = 433)
Overan ]972 En
+ Serious TRAEs
Peripheral Sensory Neuropathy — 122 (27.7%) EV +P.
pass — 85 (19.6%) chemotherapy
Alopecia + TRAEs leading to death (per
Maculopapular Rash investigator):
Fatigue - EV +P: 4 (0.9%)
> Asthenia
ce > Diarthea
Decreased Appetite > Immune-mediated lung disease
Nausea > Multiple organ dysfunction
‘Anemia Grades 12 Grade23 139 ss PR cast 409%)
= ler erapy:
un à > Febrile neutropenia
‘Thrombocytopenia > Myocardial infarction
100.90 80 70 60 60 40 30 20 10 0 10 20 30 40 50 60 70 60 90100 > Neutropenic sepsis
Incidence, % > Sepsis
Grade 23 events were 56% in EV + P and 70% in chemotherapy arms
* Data ct August ©, 2023. TRAES shown in igure are any grace by prefered term in 220% of patents or any grade nether arm. .
Pons Ta ESMO 2023 A ROY a PeerView.com
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EV +P (n= 440) Chemo (n = 433)
Overan ]972 En
+ Serious TRAEs
Peripheral Sensory Neuropathy — 122 (27.7%) EV +P.
pass — 85 (19.6%) chemotherapy
Alopecia + TRAEs leading to death (per
Maculopapular Rash investigator):
Fatigue - EV +P: 4 (0.9%)
> Asthenia
ce > Diarthea
Decreased Appetite > Immune-mediated lung disease
Nausea > Multiple organ dysfunction
‘Anemia Grades 12 Grade23 139 ss PR cast 409%)
= ler erapy:
un à > Febrile neutropenia
‘Thrombocytopenia > Myocardial infarction
100.90 80 70 60 60 40 30 20 10 0 10 20 30 40 50 60 70 60 90100 > Neutropenic sepsis
Incidence, % > Sepsis
Grade 23 events were 56% in EV + P and 70% in chemotherapy arms
* Data ct August ©, 2023. TRAES shown in igure are any grace by prefered term in 220% of patents or any grade nether arm. .
Pons Ta ESMO 2023 A ROY a PeerView.com
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Erdafitinib in FGFR-Altered Metastatic or Unresectable UC
Phase 2 BLC2001**:
Erdafitinib Monotherapy
+ Long-term efficacy outcomes
showed that patients derived
DOR, PFS, and OS benefit from
dafitinib, regardless
of FGFR alteration type, tumor
location, presence of visceral
metastases, or prior treatment
with immune checkpoint inhibitor
19: Accelerated FDA approval
for mUC with an FGFR3- or
FGFR2-activating mutation or
fusion after progression on 21 line
of platinum-containing chemo
1. Lori Y et al. N Engl J Med. 2016:381:338-
4: Lori Teta. N Engl J Med. 2023:386-1961-1971,
PeerView.com/XSE827
Phase 3 THOR’:
Where should FGFR3 inhibitors be integrated into the treatment regimens of
Key Eligibility Criteria
Patients with metastati
unresectable locally
advanced UC
Cohort 1: prior treatment
with an anti-PD-L1 agent as
monotherapy or as
combination therapy; <2 prior
lines of systemic treatment
Cohort 2: no prior treatment
with an anti-PD-L1 agent;
only 1 line of prior systemic
treatment
ECOG PS 0-2
Primary endpoint: OS
Central
screening for
FGFR
fusions or
‘mutations
patients with mUC?
Cohort 1
n=266
Secondary endpoints: PFS, ORR, PROs, DOR, safety
8. 2. Necchi A et al. Ann Oncol. 2020:31(supp 45860. 3. Siefker-Radike et al. Lancet Oncol 20222324
orally
21-d cycle
Vinflunine y
Q3W + docetaxel
Erdafitinib 8 mg orally
Ince daily for 21 din a
Pembrolizumab
PeerView.com
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Phase 2 BLC2001**:
Erdafitinib Monotherapy
+ Long-term efficacy outcomes
showed that patients derived
DOR, PFS, and OS benefit from
dafitinib, regardless
of FGFR alteration type, tumor
location, presence of visceral
metastases, or prior treatment
with immune checkpoint inhibitor
19: Accelerated FDA approval
for mUC with an FGFR3- or
FGFR2-activating mutation or
fusion after progression on 21 line
of platinum-containing chemo
1. Lori Y et al. N Engl J Med. 2016:381:338-
4: Lori Teta. N Engl J Med. 2023:386-1961-1971,
PeerView.com/XSE827
Phase 3 THOR’:
Where should FGFR3 inhibitors be integrated into the treatment regimens of
Key Eligibility Criteria
Patients with metastati
unresectable locally
advanced UC
Cohort 1: prior treatment
with an anti-PD-L1 agent as
monotherapy or as
combination therapy; <2 prior
lines of systemic treatment
Cohort 2: no prior treatment
with an anti-PD-L1 agent;
only 1 line of prior systemic
treatment
ECOG PS 0-2
Primary endpoint: OS
Central
screening for
FGFR
fusions or
‘mutations
patients with mUC?
Cohort 1
n=266
Secondary endpoints: PFS, ORR, PROs, DOR, safety
8. 2. Necchi A et al. Ann Oncol. 2020:31(supp 45860. 3. Siefker-Radike et al. Lancet Oncol 20222324
orally
21-d cycle
Vinflunine y
Q3W + docetaxel
Erdafitinib 8 mg orally
Ince daily for 21 din a
Pembrolizumab
PeerView.com
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Phase 3 THOR: Cohort 1
(Erdafitinib Versus Chemotherapy)"
MOS: 12.1 mo vs 7.8 mo =
HR = 0.64 (95% Cl, 0.47-0.88)
P= 005
mPFS: 5.6 mo vs 2.7 mo
HR = 0.58 (95% Cl, 0.44-0.78)
1002
a im, ©
A E a
= ERDA is
neo
SOTA TT A
a Time Since Randomization, mo leas Time Since Randomization, mo
PEA lee mn ee eT ae
Gene 1 8 0 0 8 D 0 ts 22100000 m mane 4 1 à 1 1 4 0 0 o
Based on these interim analyses, IMDC
recommended to stop the study, unblind data,
and cross over patients from chemo to erdafitinib
"Median follow-up: 16.9 mont a
Foret et a Meng Med 2023200:1001-1071 PeerView.com
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(Erdafitinib Versus Chemotherapy)"
MOS: 12.1 mo vs 7.8 mo =
HR = 0.64 (95% Cl, 0.47-0.88)
P= 005
mPFS: 5.6 mo vs 2.7 mo
HR = 0.58 (95% Cl, 0.44-0.78)
1002
a im, ©
A E a
= ERDA is
neo
SOTA TT A
a Time Since Randomization, mo leas Time Since Randomization, mo
PEA lee mn ee eT ae
Gene 1 8 0 0 8 D 0 ts 22100000 m mane 4 1 à 1 1 4 0 0 o
Based on these interim analyses, IMDC
recommended to stop the study, unblind data,
and cross over patients from chemo to erdafitinib
"Median follow-up: 16.9 mont a
Foret et a Meng Med 2023200:1001-1071 PeerView.com
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Phase 3 THOR: Cohort 1
(Erdafitinib Versus Chemotherapy)?
FDA Approved for
Locally Advanced or
mUC With Select FGFR3
ORR: 45.6 Alterations Progressing
on 21 PD-A/PD-L1
à Inhibitor?
RR, 3.94 (95% Cl, 2.37-6.57)
P<.001
20
Patients, %
ORR: 11.5 CR:0.8
—(n= 1)
10
Erdafitinib Chemotherapy
(n= 136) (n = 130)
à Median follow-up: 15.9 months.
1. Loni Total. N Engl J Med. 2023:380:1961-1971, 2. hips hw fda govldugs/resources-informaton-approved:-drugs/ide-approves-erdaftini-ocalyadvanced-
‘oemetastate-urthelal- carcinoma,
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(Erdafitinib Versus Chemotherapy)?
FDA Approved for
Locally Advanced or
mUC With Select FGFR3
ORR: 45.6 Alterations Progressing
on 21 PD-A/PD-L1
à Inhibitor?
RR, 3.94 (95% Cl, 2.37-6.57)
P<.001
20
Patients, %
ORR: 11.5 CR:0.8
—(n= 1)
10
Erdafitinib Chemotherapy
(n= 136) (n = 130)
à Median follow-up: 15.9 months.
1. Loni Total. N Engl J Med. 2023:380:1961-1971, 2. hips hw fda govldugs/resources-informaton-approved:-drugs/ide-approves-erdaftini-ocalyadvanced-
‘oemetastate-urthelal- carcinoma,
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Phase 3 THOR: Cohort 21
Erdafitinib vs Pembrolizumab
ORR: 40.0 RR, 1.85 (95% Cl, 132259)
Be oo
Median 08 so
ERDA: 109 mo (95% Cl, 9226)
PEMBRO: 111 mo (8% Cl 87-138)
Pr x»
® 2 CR:45
4 = 5 (n= 8)
8. 2 2 (028)
&
» ES 1
ROA
> o
(ERERREEEEEEEEEEEEENY) Erdafitinib Pembrolizumab
E Time Since Randomization, mo (n= 175) (n= 176)
a Erdafitinib — Pembrolizumab
mPFS, mo 44 27
Primary endpoint was not met; no significant difference in oe 3 144
mOS between erdafitinib and pembrolizumab
Erdafitinib demonstrated numerically better PFS
and ORR but shorter DOR versus pembrolizumab
PeerView.com
1. Sieker-Radike A et al. Ann Oncol 2024:35:107-117
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
Erdafitinib vs Pembrolizumab
ORR: 40.0 RR, 1.85 (95% Cl, 132259)
Be oo
Median 08 so
ERDA: 109 mo (95% Cl, 9226)
PEMBRO: 111 mo (8% Cl 87-138)
Pr x»
® 2 CR:45
4 = 5 (n= 8)
8. 2 2 (028)
&
» ES 1
ROA
> o
(ERERREEEEEEEEEEEEENY) Erdafitinib Pembrolizumab
E Time Since Randomization, mo (n= 175) (n= 176)
a Erdafitinib — Pembrolizumab
mPFS, mo 44 27
Primary endpoint was not met; no significant difference in oe 3 144
mOS between erdafitinib and pembrolizumab
Erdafitinib demonstrated numerically better PFS
and ORR but shorter DOR versus pembrolizumab
PeerView.com
1. Sieker-Radike A et al. Ann Oncol 2024:35:107-117
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
Using Erdafitinib Therapy in the Clinic:
Tactics for Safety Management’
General Guidance
+ FGFR3 inhibitors associated with unique AEs + Monitor for skin and nail toxicities, referring to
+ Oral hygiene critical; mucositis and other oral dermatology and podiatry as needed
toxicities a concern + Close monitoring and supportive care important
Hyperphosphatemia Ocular Toxicities
+ Erdafitinib also inhibits FGFR signaling + Recommended ophthalmologic examinations
in the proximal renal tubule, impairing — Monthly for first 4 mo; every 3 mo thereafter
function of the sodium-dependent — At any time for visual symptoms
phosphate co-transporter o + For any occurrence of central serous
+ Dietary phosphate may require restriction retinopathy (CSR)/retinal pigment epithelial
— Consult a nutrition professional detachment (RPED):
(eg, registered dietitian, nutritionist) — Withhold erdafitinib; discontinue permanently
for individualized dietary planning if symptoms do not resolve in 4 wk
— Consider adding a non-calcium-containing - Discontinue permanently for grade 4
phosphate binder (eg, sevelamer carbonate) CSR/RPED
1 LañetY etal N Engl Med, 2019:201239:49, 2 Star Rate etal, Lancet Oncol, 202223249259, PeerView.com
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
Tactics for Safety Management’
General Guidance
+ FGFR3 inhibitors associated with unique AEs + Monitor for skin and nail toxicities, referring to
+ Oral hygiene critical; mucositis and other oral dermatology and podiatry as needed
toxicities a concern + Close monitoring and supportive care important
Hyperphosphatemia Ocular Toxicities
+ Erdafitinib also inhibits FGFR signaling + Recommended ophthalmologic examinations
in the proximal renal tubule, impairing — Monthly for first 4 mo; every 3 mo thereafter
function of the sodium-dependent — At any time for visual symptoms
phosphate co-transporter o + For any occurrence of central serous
+ Dietary phosphate may require restriction retinopathy (CSR)/retinal pigment epithelial
— Consult a nutrition professional detachment (RPED):
(eg, registered dietitian, nutritionist) — Withhold erdafitinib; discontinue permanently
for individualized dietary planning if symptoms do not resolve in 4 wk
— Consider adding a non-calcium-containing - Discontinue permanently for grade 4
phosphate binder (eg, sevelamer carbonate) CSR/RPED
1 LañetY etal N Engl Med, 2019:201239:49, 2 Star Rate etal, Lancet Oncol, 202223249259, PeerView.com
PeerView.com/XSE827 Copyright © 2000-2024, PeerView
Charles: A Patient With mUC
Panel Discuss
66-year-old presented with hematuria
due to bladder mass
Urine cytology and TURBT:
urothelial carcinoma
CT CAP: several retroperitoneal
and pelvic lymph nodes
— CrCl 60 mL/min
— ECOG PS 1
— Current smoker
— History of neuropathy
— No autoimmune disease, not on steroids
— No FGFR alterations
What options would you discuss
with Charles?
PeerView.com/XSE827
PeerView.com
Copyright © 2000-2024, Peerview
Panel Discuss
66-year-old presented with hematuria
due to bladder mass
Urine cytology and TURBT:
urothelial carcinoma
CT CAP: several retroperitoneal
and pelvic lymph nodes
— CrCl 60 mL/min
— ECOG PS 1
— Current smoker
— History of neuropathy
— No autoimmune disease, not on steroids
— No FGFR alterations
What options would you discuss
with Charles?
PeerView.com/XSE827
PeerView.com
Copyright © 2000-2024, Peerview
Tool to Support Patients Searching
for Clinical Trials in Bladder Cancer
SU
a The BCAN Clinical Trials dashboard
BCAN. can be used to find a trial that fits an
ans individual patient's needs.
+ Healthcare professionals can save trials and email
them to patients for further discussion at their next visit
+ Patients can search by geographic area and find trials
close to/convenient for them
See the BCAN Practice Aid for full details on
the BCAN website, a QR code for professionals
to download resources for patients, and more!
PeerView.com
Copyright © 2000-2024, PeerView
PeerView.com/XSE827
for Clinical Trials in Bladder Cancer
SU
a The BCAN Clinical Trials dashboard
BCAN. can be used to find a trial that fits an
ans individual patient's needs.
+ Healthcare professionals can save trials and email
them to patients for further discussion at their next visit
+ Patients can search by geographic area and find trials
close to/convenient for them
See the BCAN Practice Aid for full details on
the BCAN website, a QR code for professionals
to download resources for patients, and more!
PeerView.com
Copyright © 2000-2024, PeerView
PeerView.com/XSE827
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