Achieving Optimal SCLC Care With Established and Innovative Therapies: Latest Evidence, Key Ongoing Trials, and Practical Considerations for Real-World Practice
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About This Presentation
Chair and Presenters Ticiana Leal, MD, Mark M. Awad, MD, PhD, Professor Byoung Chul Cho, MD, PhD, and Carl M. Gay, MD, PhD, discuss small cell lung cancer in this CME/MOC/NCPD/AAPA/IPCE activity titled “Achieving Optimal SCLC Care With Established and Innovative Therapies: Latest Evidence, Key Ong...
Slide Content
Achieving Optimal SCLC Care
With Established and Innovative Therapies
Latest Evidence, Key Ongoing Trials, and Practical Considerations
Ticiana Leal, MD for Real-World Practice
Associate Professor Carl M. Gay, MD, PhD
Department of Hematology & Oncology Assistant Professor
Director, Thoracic Medical Oncology Department of Thoracic/Head and Neck
Winship Cancer Institute Medical Oncology
Emory University School of Medicine Division of Cancer Medicine
Atlanta, Georgia The University of Texas MD Anderson Cancer
Center
Houston, Texas
Mark M. Awad, MD, PhD
Director of Clinical Research
Program Director Prof. Byoung Chul Cho, MD, PhD
‘Advanced Fellowship in Thoracic Oncology Professor, Division of Medical Oncology
Physician Yonsei Cancer Center
Associate Professor of Medicine ‘Yonsei University College of Medicine
Harvard Medical School ‘Seoul, South Korea
Associate Chief of the Lowe Center for Thoracic Oncology
Dana-Farber Cancer institute
Boston, Massachusetts
Go online to access full CME/MOC/NCPD/AAPA/IPCE information, including faculty disclosures.
Copyright © 2000-2024, PeerView
With Established and Innovative Therapies
Latest Evidence, Key Ongoing Trials, and Practical Considerations
Ticiana Leal, MD for Real-World Practice
Associate Professor Carl M. Gay, MD, PhD
Department of Hematology & Oncology Assistant Professor
Director, Thoracic Medical Oncology Department of Thoracic/Head and Neck
Winship Cancer Institute Medical Oncology
Emory University School of Medicine Division of Cancer Medicine
Atlanta, Georgia The University of Texas MD Anderson Cancer
Center
Houston, Texas
Mark M. Awad, MD, PhD
Director of Clinical Research
Program Director Prof. Byoung Chul Cho, MD, PhD
‘Advanced Fellowship in Thoracic Oncology Professor, Division of Medical Oncology
Physician Yonsei Cancer Center
Associate Professor of Medicine ‘Yonsei University College of Medicine
Harvard Medical School ‘Seoul, South Korea
Associate Chief of the Lowe Center for Thoracic Oncology
Dana-Farber Cancer institute
Boston, Massachusetts
Go online to access full CME/MOC/NCPD/AAPA/IPCE information, including faculty disclosures.
Copyright © 2000-2024, PeerView
PeerView.com/HXN827
Our Goals for Today
Equip you with knowledge and skills to make the most of the established
and new approved therapies for SCLC
Enhance your awareness of emerging therapies showing promise in SCLC
Augment your ability to develop individualized treatment plans, manage AEs,
and improve outcomes in SCLC
Our Goals for Today
Equip you with knowledge and skills to make the most of the established
and new approved therapies for SCLC
Enhance your awareness of emerging therapies showing promise in SCLC
Augment your ability to develop individualized treatment plans, manage AEs,
and improve outcomes in SCLC
LUNGevity as Our Partner: Access Survivorship and
Support Services for Your Patients and Their Care Partners
For Patients &
Caregivers
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Support Services for Your Patients and Their Care Partners
For Patients &
Caregivers
PeerView.com/HXN827 Copyright © 2000-2024, PeerView
UNGevity as Our Partner: A Focus on SCLC
LUNGevity is working with SCLC experts ES me
to create an interactive journey map ar tie
LUNGevity is partnering with Dr. Misty Shields to launch the | si
SMALL CELL SMASHERS Group through social media ©
Small Cell Lung
| About Small Cell Lung Cancer
Introducing Small» interested
Cell Smashers:...
CRE o
PeerView.com/HXN827 Copyright © 2000-2024, PeerView
LUNGevity is working with SCLC experts ES me
to create an interactive journey map ar tie
LUNGevity is partnering with Dr. Misty Shields to launch the | si
SMALL CELL SMASHERS Group through social media ©
Small Cell Lung
| About Small Cell Lung Cancer
Introducing Small» interested
Cell Smashers:...
CRE o
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LUNGevity as Our Partner: SCLC Patient Perspectives
Patients and caregivers feel
+ They have not been well
prepared for the diagnosis
of SCLC, regardless of
whether they have limited
or extensive stage disease
Hopeful and stated that their
providers are very
supportive and have been
accessible and answered
questions thoroughly
The hopelessness of the
disease was “swept
under the rug”
Emphasis was placed on
responding to first-line
therapy and then no real
information to prepare them
for what comes next
PeerView.com/HXN827
For SCLC survivors there
is a feeling that they are living
in an NSCLC world where
there are few resources
specifically for them
Many patients and their care
partners reported that they
appreciate when written
materials are reviewed with
them by the HCP and not
just handed to them
Patients’ perception is that
“everything on the internet
is so negative”
Only 2 out of 6 patients
interviewed stated that
a clinical trial had been
mentioned by their
provider
Very few of those
interviewed had ever
sought out resources
from advocacy groups
Very few had ever engaged
in support groups
Most were unaware of
current clinical trials or
any new treatments on
the horizon
Most stated they would like
to hear some positive news
around treatments
Caregivers felt unprepared
for the rapidity of the
progression of the disease
Copyright © 2000-2024, PeerView
Patients and caregivers feel
+ They have not been well
prepared for the diagnosis
of SCLC, regardless of
whether they have limited
or extensive stage disease
Hopeful and stated that their
providers are very
supportive and have been
accessible and answered
questions thoroughly
The hopelessness of the
disease was “swept
under the rug”
Emphasis was placed on
responding to first-line
therapy and then no real
information to prepare them
for what comes next
PeerView.com/HXN827
For SCLC survivors there
is a feeling that they are living
in an NSCLC world where
there are few resources
specifically for them
Many patients and their care
partners reported that they
appreciate when written
materials are reviewed with
them by the HCP and not
just handed to them
Patients’ perception is that
“everything on the internet
is so negative”
Only 2 out of 6 patients
interviewed stated that
a clinical trial had been
mentioned by their
provider
Very few of those
interviewed had ever
sought out resources
from advocacy groups
Very few had ever engaged
in support groups
Most were unaware of
current clinical trials or
any new treatments on
the horizon
Most stated they would like
to hear some positive news
around treatments
Caregivers felt unprepared
for the rapidity of the
progression of the disease
Copyright © 2000-2024, PeerView
Clinical and Research Accelerator
How Can We Optimize the Current
First-Line Treatment Options for ES-SCLC?
Ticiana Leal, MD
Associate Professor
Department of Hematology & Oncology
Director, Thoracic Medical Oncology
Winship Cancer Institute
Emory University School of Medicine
Atlanta, Georgia
Copyright © 2000-2024, PeerView
How Can We Optimize the Current
First-Line Treatment Options for ES-SCLC?
Ticiana Leal, MD
Associate Professor
Department of Hematology & Oncology
Director, Thoracic Medical Oncology
Winship Cancer Institute
Emory University School of Medicine
Atlanta, Georgia
Copyright © 2000-2024, PeerView
A Case to Consider
79-year-old woman with a PMHx of HTN, COPD, and HLD, as well as a 45 pack-year smoking history
presents to PCP c/o cough and generalized fatigue x 3 months; ECOG PS 1
Initial CXR reveals a LUL opacity; follow-up CT of the chest reveals a 4-cm lobulated LUL mass
with associated L hilar and mediastinal LAD
She underwent a bronchoscopy and biopsy that revealed the diagnosis of SCLC
MRI brain is negative; PET/CT showed multiple FDG avid hepatic hypodensities and extensive
bone marrow uptake c/w skeletal metastasis
She is presenting to your medical oncology clinic to discuss further management
PeerView.com/HXN827 Copyright © 2000-2024, PeerView
79-year-old woman with a PMHx of HTN, COPD, and HLD, as well as a 45 pack-year smoking history
presents to PCP c/o cough and generalized fatigue x 3 months; ECOG PS 1
Initial CXR reveals a LUL opacity; follow-up CT of the chest reveals a 4-cm lobulated LUL mass
with associated L hilar and mediastinal LAD
She underwent a bronchoscopy and biopsy that revealed the diagnosis of SCLC
MRI brain is negative; PET/CT showed multiple FDG avid hepatic hypodensities and extensive
bone marrow uptake c/w skeletal metastasis
She is presenting to your medical oncology clinic to discuss further management
PeerView.com/HXN827 Copyright © 2000-2024, PeerView
CASPIAN Study Design:
Durvalumab + Tremelimumab + EP in ES-SCLC!
+» Treatment-naive ES-SCLC
+ WHOPSOor1
+ Asymptomatic or treated
and stable brain
metastases permitted
* Life expectancy 212 wk
+ Measurable disease per
RECIST v1.1
N = 805 (randomized)
Stratified by
+ Planned platinum
(carboplatin vs cisplatin)
1. Paz-Ares LG et al ASCO 2020. Abstract 9002,
PeerView.com/HXN827
Durvalumab
+ tremelimumab + EP
every 3 weeks for 4 cycles
Durvalumab
every 4 weeks until PD
Durvalumab
every 4 weeks until PD
Durvalumab + EP
every 3 weeks for 4 cycles
EP
every 3 weeks for up to 6 cycles
Optional PCI
+ Primary endpoint: OS
+ Secondary endpoints: PFS, ORR, safety and tolerability,
and patient-reported outcomes
PeerView.com
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Durvalumab + Tremelimumab + EP in ES-SCLC!
+» Treatment-naive ES-SCLC
+ WHOPSOor1
+ Asymptomatic or treated
and stable brain
metastases permitted
* Life expectancy 212 wk
+ Measurable disease per
RECIST v1.1
N = 805 (randomized)
Stratified by
+ Planned platinum
(carboplatin vs cisplatin)
1. Paz-Ares LG et al ASCO 2020. Abstract 9002,
PeerView.com/HXN827
Durvalumab
+ tremelimumab + EP
every 3 weeks for 4 cycles
Durvalumab
every 4 weeks until PD
Durvalumab
every 4 weeks until PD
Durvalumab + EP
every 3 weeks for 4 cycles
EP
every 3 weeks for up to 6 cycles
Optional PCI
+ Primary endpoint: OS
+ Secondary endpoints: PFS, ORR, safety and tolerability,
and patient-reported outcomes
PeerView.com
Copyright © 2000-2024, PeerView
CASPIAN 3-Year OS Update: Durvalumab + EP vs Ep!:2a
‘ Durva + EP EP
1.
Events, niN (%) 2211268 (82.5) 2481269 (92.2)
os MOS, mo (95% Cl) 129113147) 105 93-112)
£ HR (95% Cl) 0.71 (0.60-0.86)
5 06 Nominal P value 0003
é Median follow-up in censored patients: 39.4 mo (range, 0.1-47.5)
04
a 32.0%
° 22.9%
02 Durva + EP
3 13.9%
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51
Time Since Randomization, mo
No, at Risk
Duva+EP 268 244 214 177 140 109 86 70 60 54 50 46 3% 26 13 3 0 0
ep 269 243 212 166 104 82 64 51 36 24 19 17 13 10 3 0 0 0
* Data ato March 22, 2021 A
1.Paz-Ares LG et al ESMO 2021. Abstract LBABI. 2. Paz-Ares LG et al. ESMO Open. 2022:7: 100408. PeerView.com
PeerView.com/HXN827 Copyright © 2000-2024, PeerView
‘ Durva + EP EP
1.
Events, niN (%) 2211268 (82.5) 2481269 (92.2)
os MOS, mo (95% Cl) 129113147) 105 93-112)
£ HR (95% Cl) 0.71 (0.60-0.86)
5 06 Nominal P value 0003
é Median follow-up in censored patients: 39.4 mo (range, 0.1-47.5)
04
a 32.0%
° 22.9%
02 Durva + EP
3 13.9%
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51
Time Since Randomization, mo
No, at Risk
Duva+EP 268 244 214 177 140 109 86 70 60 54 50 46 3% 26 13 3 0 0
ep 269 243 212 166 104 82 64 51 36 24 19 17 13 10 3 0 0 0
* Data ato March 22, 2021 A
1.Paz-Ares LG et al ESMO 2021. Abstract LBABI. 2. Paz-Ares LG et al. ESMO Open. 2022:7: 100408. PeerView.com
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Impact of Brain Metastases on Treatment Patterns
and Outcomes in CASPIAN!
OS in Patients With Brain Metastases at Baseline
me
zen
Der wen lic ia
ES Bawa ME Migas A
Pen me rem Randomization, mo
EE ge re 4 1 9 8 8
OS in Patients Without Brain Metastases at Baseline
sen she nis
DORE EEE
1. Chen Y et a. JTO Cin Res Rep. 2022:3:100320.
PeerView.com/HXN827
PFS in Patients With Brain Metastases at Baseline
E Nae
ose From
a ea 0 er
PFS in Patients Without Brain Metastases at Baseline
ahr eee ES sas ier
i:
da
sic Tine From Randomization,
PeerView.com
Copyright © 2000-2024, PeerView
and Outcomes in CASPIAN!
OS in Patients With Brain Metastases at Baseline
me
zen
Der wen lic ia
ES Bawa ME Migas A
Pen me rem Randomization, mo
EE ge re 4 1 9 8 8
OS in Patients Without Brain Metastases at Baseline
sen she nis
DORE EEE
1. Chen Y et a. JTO Cin Res Rep. 2022:3:100320.
PeerView.com/HXN827
PFS in Patients With Brain Metastases at Baseline
E Nae
ose From
a ea 0 er
PFS in Patients Without Brain Metastases at Baseline
ahr eee ES sas ier
i:
da
sic Tine From Randomization,
PeerView.com
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IMpower133 Study Desig
Atezolizumab + Chemotherapy in ES-SCLC!
Induction (4 x 21-day cycles) Maintenance
+ Measurable ES-SCLC Atezolizumab 1,200 mg IV ond 1
(RECIST v1.1) + carboplatin AUC 5 mg/mL/min IV on d 1 M Atezolizumab
+ ECOG PS 0 or 1 + etoposide 100 mg/m? IV on d 1-3
+ No prior systemic & Treat until
treatment for ES-SCLC PD or loss
+ Treated asymptomatic of oo
brain metastases were
eligible Placebo
+ carboplatin AUC 5 mg/mL/min IV on d 1 Placebo
N=403 + etoposide 100 mg/m? IV on d 1
Survival follow-up
Stratified by PCI per local SOC
+ Sex (male vs female) + Coprimary endpoints: OS, investigator-assessed PFS
+ ECOG PS (0 vs 1) A
a FR NAS) + Key secondary endpoints: ORR, DOR, safety
1. Hom Letal. N Engl J Med. 2018:379:2220-2220, PeerView.com
PeerView.com/HXN827 Copyright © 2000-2024, Peerview
Atezolizumab + Chemotherapy in ES-SCLC!
Induction (4 x 21-day cycles) Maintenance
+ Measurable ES-SCLC Atezolizumab 1,200 mg IV ond 1
(RECIST v1.1) + carboplatin AUC 5 mg/mL/min IV on d 1 M Atezolizumab
+ ECOG PS 0 or 1 + etoposide 100 mg/m? IV on d 1-3
+ No prior systemic & Treat until
treatment for ES-SCLC PD or loss
+ Treated asymptomatic of oo
brain metastases were
eligible Placebo
+ carboplatin AUC 5 mg/mL/min IV on d 1 Placebo
N=403 + etoposide 100 mg/m? IV on d 1
Survival follow-up
Stratified by PCI per local SOC
+ Sex (male vs female) + Coprimary endpoints: OS, investigator-assessed PFS
+ ECOG PS (0 vs 1) A
a FR NAS) + Key secondary endpoints: ORR, DOR, safety
1. Hom Letal. N Engl J Med. 2018:379:2220-2220, PeerView.com
PeerView.com/HXN827 Copyright © 2000-2024, Peerview
IMpower133: Atezolizumab + Chemotherapy Updated OS!
100 Atezolizumab + CP/ET Placebo + CPIET
(n= 201) (n= 202)
bi ‘Median OS, mo 123 103
80 (85% Cl) (10.8-15.8) (03-113)
70: HR (95% Cl) 0.76 (0.60-0.95)
P 0154"
60.
50
40
30.
20:
22.
OS, %
Atezolizumab + CP/ET
21.0%
10 Placebo + CPIET
o
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32
same Time, mo
Alezozumab +CPET 201 187 180 159 190 109 99 08 75 61 St 2% 21 8 1
Placebo +CPET 22 189 183 AD 191 97 TA OOO OA
"Ps provided for descptve purposes. CCOD: January 24, 2019. N
1ÉREG M ea ESMO 2019. abeeast 2070 PeerView.com
PeerView.com/HXN827 Copyright © 2000-2024, PeerView
100 Atezolizumab + CP/ET Placebo + CPIET
(n= 201) (n= 202)
bi ‘Median OS, mo 123 103
80 (85% Cl) (10.8-15.8) (03-113)
70: HR (95% Cl) 0.76 (0.60-0.95)
P 0154"
60.
50
40
30.
20:
22.
OS, %
Atezolizumab + CP/ET
21.0%
10 Placebo + CPIET
o
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32
same Time, mo
Alezozumab +CPET 201 187 180 159 190 109 99 08 75 61 St 2% 21 8 1
Placebo +CPET 22 189 183 AD 191 97 TA OOO OA
"Ps provided for descptve purposes. CCOD: January 24, 2019. N
1ÉREG M ea ESMO 2019. abeeast 2070 PeerView.com
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IMbrella A: An Extension Study of IMpower1331
IMpower133 Study IMbrella A Extension Study
Patients were eligible
if they continued to receive
atezolizumab at Atezolizumab
study closure or were and/or survival
in the survival follow-up follow-up
(n= 18)
1. Liu Seta. WLC 2023. Oral presentation OAD1.04. PeerView.com
PeerView.com/HXN827 Copyright © 2000-2024, Peerview
IMpower133 Study IMbrella A Extension Study
Patients were eligible
if they continued to receive
atezolizumab at Atezolizumab
study closure or were and/or survival
in the survival follow-up follow-up
(n= 18)
1. Liu Seta. WLC 2023. Oral presentation OAD1.04. PeerView.com
PeerView.com/HXN827 Copyright © 2000-2024, Peerview
IMpower133 and IMbrella A: Long-Term OS1
‘Atez0 + CPIET Placebo + CPIET
= 209) (a= 202)
100
en 159 gen 168 (837) IMpower133 + IMbrella A ower133 Only
Median OS, mo (95% ci) 123 (108-158) 103 (03-113)
OS Rate,y Atezo + CPIET, Placebo + CPIET,
% (95% CI)
02)
e
Aezo + CPIET median follow-up: 59.4 mo (range, 0-72)
# w Placebo + CPIET median follow-up: 26.4 mo (range, 0-34.4) a ee) a8 (0248)
g yee 08, 12% 2 22 (1628) 16 (1421)
”
3 46 (11-21) Neo
a Atezolizumab + CPIET 4 13 (8-18) NE
5 1207) Ne
o
03 © © W205 10 24 da 27 30 39 30 30 42 45 49 81 58 87 60 63 OOD 7276
Time, mo
Per
use CET 201 102150921 99 81 01 48 39 39 30 30 BBW 515 UM M 12 11 10 € 7 2
Pate + CPET men 68 9 M SN 3 2 0 0 0 0 0 0 0 0 0 0 8 © ©
+ Cinca ef date: Marc 10.2020
208 rates were NE inthe contol arm as or to re A was not permite —
1. Lu S etal WCLC 2023, Oral presentation OAO' 04. PeerView.com
PeerView.com/HXN827 Copyright © 2000-2024, PeerView
‘Atez0 + CPIET Placebo + CPIET
= 209) (a= 202)
100
en 159 gen 168 (837) IMpower133 + IMbrella A ower133 Only
Median OS, mo (95% ci) 123 (108-158) 103 (03-113)
OS Rate,y Atezo + CPIET, Placebo + CPIET,
% (95% CI)
02)
e
Aezo + CPIET median follow-up: 59.4 mo (range, 0-72)
# w Placebo + CPIET median follow-up: 26.4 mo (range, 0-34.4) a ee) a8 (0248)
g yee 08, 12% 2 22 (1628) 16 (1421)
”
3 46 (11-21) Neo
a Atezolizumab + CPIET 4 13 (8-18) NE
5 1207) Ne
o
03 © © W205 10 24 da 27 30 39 30 30 42 45 49 81 58 87 60 63 OOD 7276
Time, mo
Per
use CET 201 102150921 99 81 01 48 39 39 30 30 BBW 515 UM M 12 11 10 € 7 2
Pate + CPET men 68 9 M SN 3 2 0 0 0 0 0 0 0 0 0 0 8 © ©
+ Cinca ef date: Marc 10.2020
208 rates were NE inthe contol arm as or to re A was not permite —
1. Lu S etal WCLC 2023, Oral presentation OAO' 04. PeerView.com
PeerView.com/HXN827 Copyright © 2000-2024, PeerView
Sites of Progression in IMpower133 (ITT Population)!
Sites of New Lesions
20 in Patients Who Progressed®
18
16
mAtezo + CP/ET
“ 124
PD 160 (79.6) 173 (856) nieto Rene
= 12 0.4! 104102 109
PD on target = 10
Be 103 (51.2) 114 (56.4) EM
PD on nontarget E
a 32 (15.9) 47 (23.3) 6
PD on new lesion 86 (42.8) 99 (49.0) A
2
o ll L 1
Brain Lung Lymph Liver Adrenal Bone Pleura
Node Gland
Hs A et at ASTRO 2000 A PeerView.com
PeerView.com/HXN827 Copyright © 2000-2024, Peerview
Sites of New Lesions
20 in Patients Who Progressed®
18
16
mAtezo + CP/ET
“ 124
PD 160 (79.6) 173 (856) nieto Rene
= 12 0.4! 104102 109
PD on target = 10
Be 103 (51.2) 114 (56.4) EM
PD on nontarget E
a 32 (15.9) 47 (23.3) 6
PD on new lesion 86 (42.8) 99 (49.0) A
2
o ll L 1
Brain Lung Lymph Liver Adrenal Bone Pleura
Node Gland
Hs A et at ASTRO 2000 A PeerView.com
PeerView.com/HXN827 Copyright © 2000-2024, Peerview
Intracranial Progression in IMpower133 (ITT Population)!
Atezo + Ci Placebo + CPIET
(n=201) (n=202)
‘Median time to intracranial
100 en 202(11.0-NE) 105 (67-173)
- HR (95% CI) 0.66 (0.44-4.0)
e ones
æ 60
g
G40 Atezo + CP/ET
Placebo + CP/ET
20
0
No, at Risk Time, mo
Atezo+CPIET 201 174 154 84 66 47 38 36 32 26 20 15 9 2 1
Placebo +CP/ET 202 183 156 56 35 2 15 13 12 9 6 5 2 0 0
2 Foe dessiptive purposes A
1 nig ca ASTRO 2020 Abstract LAS, PeerView.com
PeerView.com/HXN827 Copyright © 2000-2024, PeerView
Atezo + Ci Placebo + CPIET
(n=201) (n=202)
‘Median time to intracranial
100 en 202(11.0-NE) 105 (67-173)
- HR (95% CI) 0.66 (0.44-4.0)
e ones
æ 60
g
G40 Atezo + CP/ET
Placebo + CP/ET
20
0
No, at Risk Time, mo
Atezo+CPIET 201 174 154 84 66 47 38 36 32 26 20 15 9 2 1
Placebo +CP/ET 202 183 156 56 35 2 15 13 12 9 6 5 2 0 0
2 Foe dessiptive purposes A
1 nig ca ASTRO 2020 Abstract LAS, PeerView.com
PeerView.com/HXN827 Copyright © 2000-2024, PeerView
IMforte: 1L Lurbinectedin in Combination
With Atezolizumab!
A phase 3 study evaluating the efficacy and safety of atezolizumab plus lurbinectedin as maintenance
treatment compared with atezolizumab alone
Induction Phase
Agez18 y
ES-SCLC
Treatment-ree for at Patients with
least 6 mo since last ‘ongoing response
‘chemotherapy or Four 21-4 or SD per Treatment until
radiotherapy in re of RECIST v1.1% disease
participants who were O toxicities attributed progression per
treated with curative 1200 ma to prior induction RECIST v1.1
intent for LS-SCLC * catboplatin || anti-cancer therapy or death
No prior systemic A ‘or PCI resolved to
therapy for ES-SCLC grade st
+ Co-primary endpoints: independent
review facilty-assessed PFS, OS
+ Secondary endpoints: investigator-
assessed PFS, ORR, DOR, PFS, OS,
safety, prevalence of anti-drug
antibodies to atezolizumab, QOL
ECOG PS 0 or 1
No CNS metastases.
+ Fotowing the induction therapy but before randomization, parscpant may recive Prophylac canal rraiaben atthe investigator’ dscreton pe local standard
*Granulocyte eolony-stmuating factor as primary prophylais is mandatory for paricipats assigned tothe lrbinectedin-contaning arm. m
1.Paz-AresLetal. WCLC 2022. Poster EP14.01.018 PeerView.com
PeerView.com/HXN827 Copyright © 2000-2024, PeerView
With Atezolizumab!
A phase 3 study evaluating the efficacy and safety of atezolizumab plus lurbinectedin as maintenance
treatment compared with atezolizumab alone
Induction Phase
Agez18 y
ES-SCLC
Treatment-ree for at Patients with
least 6 mo since last ‘ongoing response
‘chemotherapy or Four 21-4 or SD per Treatment until
radiotherapy in re of RECIST v1.1% disease
participants who were O toxicities attributed progression per
treated with curative 1200 ma to prior induction RECIST v1.1
intent for LS-SCLC * catboplatin || anti-cancer therapy or death
No prior systemic A ‘or PCI resolved to
therapy for ES-SCLC grade st
+ Co-primary endpoints: independent
review facilty-assessed PFS, OS
+ Secondary endpoints: investigator-
assessed PFS, ORR, DOR, PFS, OS,
safety, prevalence of anti-drug
antibodies to atezolizumab, QOL
ECOG PS 0 or 1
No CNS metastases.
+ Fotowing the induction therapy but before randomization, parscpant may recive Prophylac canal rraiaben atthe investigator’ dscreton pe local standard
*Granulocyte eolony-stmuating factor as primary prophylais is mandatory for paricipats assigned tothe lrbinectedin-contaning arm. m
1.Paz-AresLetal. WCLC 2022. Poster EP14.01.018 PeerView.com
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SCLC Subtypes'4
+ Biologic subtypes can be established by differential expression of transcription
regulators such as
— ASCL1 (achaete-scute homologue 1)
— NEUROD1 (neurogenic differentiation factor 1)
— POU2F3 (POU class 2 homeobox 3)
+ SCLC subtypes based on neuroendocrine (SCLC-A and SCLC-N), non-neuroendocrine
(SCLC-P), and immune-infiltrated (SCLC-I) transcription signatures are potentially
promising biomarkers
1. Rudin CM etal. Nat Rev Cancer. 2019:19:289-297. 2. Gay CM etal. WCLC 2019. Abstract OAD3.06. ae
3. Gay CM et a. Cancer Cel 2021.30:346-60.7.4. Lu SV et al, ESMO Viral Plenary. VPS-2021 PeerView.com
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+ Biologic subtypes can be established by differential expression of transcription
regulators such as
— ASCL1 (achaete-scute homologue 1)
— NEUROD1 (neurogenic differentiation factor 1)
— POU2F3 (POU class 2 homeobox 3)
+ SCLC subtypes based on neuroendocrine (SCLC-A and SCLC-N), non-neuroendocrine
(SCLC-P), and immune-infiltrated (SCLC-I) transcription signatures are potentially
promising biomarkers
1. Rudin CM etal. Nat Rev Cancer. 2019:19:289-297. 2. Gay CM etal. WCLC 2019. Abstract OAD3.06. ae
3. Gay CM et a. Cancer Cel 2021.30:346-60.7.4. Lu SV et al, ESMO Viral Plenary. VPS-2021 PeerView.com
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SCLC Subtypes’
+ Biologic subtypes can be established by differential expression of transcription
regulators such as
— ASCL1 (achaete-scute homologue 1)
— NEUROD1 (neurogenic differentiation factor 1)
— POU2F3 (POU class 2 homeobox 3)
+ SCLC subtypes based on neuroendocrine (SCLC-A and SCLC-N), non-neuroendocrine
(SCLC-P), and immune-infiltrated (SCLC-I) transcription signatures are potentially
promising biomarkers
Results from gene expression al
were recently reported—associations between differer
(LTS) from IMpower133
gene expression and
1. Rudin CM tai Nat Rev Cancer 201919280297.2 Gay CM et al WLC 2019. Abstract OA03 08. —
3. Gay CM et a. Cancer Call 2021;30:346-60e7. 4. Liu SV et al, ESMO Viral Plenary. VPS-2021 PeerView.com
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+ Biologic subtypes can be established by differential expression of transcription
regulators such as
— ASCL1 (achaete-scute homologue 1)
— NEUROD1 (neurogenic differentiation factor 1)
— POU2F3 (POU class 2 homeobox 3)
+ SCLC subtypes based on neuroendocrine (SCLC-A and SCLC-N), non-neuroendocrine
(SCLC-P), and immune-infiltrated (SCLC-I) transcription signatures are potentially
promising biomarkers
Results from gene expression al
were recently reported—associations between differer
(LTS) from IMpower133
gene expression and
1. Rudin CM tai Nat Rev Cancer 201919280297.2 Gay CM et al WLC 2019. Abstract OA03 08. —
3. Gay CM et a. Cancer Call 2021;30:346-60e7. 4. Liu SV et al, ESMO Viral Plenary. VPS-2021 PeerView.com
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Distinct SCLC Subsets Experience Different Outcomes
With Chemo-Immunotherapy!
Sos IMpower133 OS (EP + Atezo) IMpower133 OS (EP + Placebo)
rum ii EN
Moo 021090)
CE x
RERSENTTETTIETI MERRELITETTITTI
ara i Time, mo ime, mo
ES
ad IMpowert33 OS by Subtype
Er H mu Lane
ei |? ole cra
cen test rn
} saca m 09 ws
ee | sen é
Pa.” saco] ——h Fe
ss
ES SQL mn 270)
Le)
1. Gay CM et al Cancer Cel 2021;9:346-60¢7 PeerView.com
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With Chemo-Immunotherapy!
Sos IMpower133 OS (EP + Atezo) IMpower133 OS (EP + Placebo)
rum ii EN
Moo 021090)
CE x
RERSENTTETTIETI MERRELITETTITTI
ara i Time, mo ime, mo
ES
ad IMpowert33 OS by Subtype
Er H mu Lane
ei |? ole cra
cen test rn
} saca m 09 ws
ee | sen é
Pa.” saco] ——h Fe
ss
ES SQL mn 270)
Le)
1. Gay CM et al Cancer Cel 2021;9:346-60¢7 PeerView.com
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Enrichment of LTS Among the SCLC-I Subtype
Associated With Atezolizumab'
Patients
E
ES ES CS
LE LE
1. Lu SV et al ESMO Virtual Plenary. VPS-2021,
PeerView.com/HXN827
SS
ZA
scLc4
mNon-LTS
LTS
+ There were nonsignificant trends
observed in the SCLC-I subset
— Inthe atezolizumab arm, 11 of 20
(55%) were LTS
— In the placebo arm, 8 of 27 (30%)
were LTS
A higher percentage of the SCLC-I subset
were LTS than non-LTS (55% vs 45%) in
the atezolizumab arm
LTS in the atezolizumab arm were not
limited to one specific subset
— Benefit was seen across all subtypes
PeerView.com
Copyright © 2000-2024, PeerView
Associated With Atezolizumab'
Patients
E
ES ES CS
LE LE
1. Lu SV et al ESMO Virtual Plenary. VPS-2021,
PeerView.com/HXN827
SS
ZA
scLc4
mNon-LTS
LTS
+ There were nonsignificant trends
observed in the SCLC-I subset
— Inthe atezolizumab arm, 11 of 20
(55%) were LTS
— In the placebo arm, 8 of 27 (30%)
were LTS
A higher percentage of the SCLC-I subset
were LTS than non-LTS (55% vs 45%) in
the atezolizumab arm
LTS in the atezolizumab arm were not
limited to one specific subset
— Benefit was seen across all subtypes
PeerView.com
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CASPIAN: OS by Molecular Subtype’
me
à D+EP nn 115 10: EP
Fk Ea sa
3 Ses à
£ os. va 173 os.
5
zZ fa os
B ga 8.
3 o
Ss 7 zum CE TE TE VETE ERC)
EA Braun er ase
at! phidd ER
3 =
i sms Y
2 =
=
SM Mirar RELw eee
E wane Timo, mo ‘cee "Time, mo.
Psat ri biiig: Per ibiidaadd
Na Ua resin ones PeerView.com
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me
à D+EP nn 115 10: EP
Fk Ea sa
3 Ses à
£ os. va 173 os.
5
zZ fa os
B ga 8.
3 o
Ss 7 zum CE TE TE VETE ERC)
EA Braun er ase
at! phidd ER
3 =
i sms Y
2 =
=
SM Mirar RELw eee
E wane Timo, mo ‘cee "Time, mo.
Psat ri biiig: Per ibiidaadd
Na Ua resin ones PeerView.com
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CASPIAN: Patients With High T-Cell Inflamed Signature
Had Numerically Longer OS in the D + EP Arm!
D+EP EP
Inflamed signature High Low High Low
MOS, months (95% CI) 15.8 (10.4-NE) 11.3(7.1-14.6) 9.4(7.3-159) 8.3(6.1-11.4)
HR, high vs low (95% Cl) 0.64 (0.31-1.32) 0.87 (0.45-1.66)
10 10
09 D+EP os EP
08 08
807 07
=
& 085 805
gos & 04
03 High = top quartile dos
02 — 02
01 Lo = rest 01
o o
0 4 8 12 16 20 26 20 32 % 40 44 48 0451216 20 20 28 32 35 40 44 de
No. at Risk Tino, mo. No. at Risk. Time, mo
Mori? 2 1 8 6 4 3 3 3 3 2 0 0 tort) o 5 3 2 1 0 0 0 0 0 0
tw 4 0 2 1 2 0 8 8 7 6 3 2 0 e aan 7121117008
1. Shrestha Y etal, ACR 2022. Abstract CTO24 PeerView.com
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Had Numerically Longer OS in the D + EP Arm!
D+EP EP
Inflamed signature High Low High Low
MOS, months (95% CI) 15.8 (10.4-NE) 11.3(7.1-14.6) 9.4(7.3-159) 8.3(6.1-11.4)
HR, high vs low (95% Cl) 0.64 (0.31-1.32) 0.87 (0.45-1.66)
10 10
09 D+EP os EP
08 08
807 07
=
& 085 805
gos & 04
03 High = top quartile dos
02 — 02
01 Lo = rest 01
o o
0 4 8 12 16 20 26 20 32 % 40 44 48 0451216 20 20 28 32 35 40 44 de
No. at Risk Tino, mo. No. at Risk. Time, mo
Mori? 2 1 8 6 4 3 3 3 3 2 0 0 tort) o 5 3 2 1 0 0 0 0 0 0
tw 4 0 2 1 2 0 8 8 7 6 3 2 0 e aan 7121117008
1. Shrestha Y etal, ACR 2022. Abstract CTO24 PeerView.com
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Coming Back to Our Case
79-year-old woman with a PMHx of HTN, COPD, and HLD, as well as a 45 pack-year smoking history
presents to PCP c/o cough and generalized fatigue x 3 months; ECOG PS 1
Initial CXR reveals a LUL opacity; follow-up CT of the chest reveals a 4-cm lobulated LUL mass
with associated L hilar and mediastinal LAD
She underwent a bronchoscopy and biopsy that revealed the diagnosis of SCLC
MRI brain is negative; PET/CT showed multiple FDG avid hepatic hypodensities and extensive
bone marrow uptake c/w skeletal metastasis
She is presenting to your medical oncology clinic to discuss further management
PeerView.com/HXN827 Copyright © 2000-2024, PeerView
79-year-old woman with a PMHx of HTN, COPD, and HLD, as well as a 45 pack-year smoking history
presents to PCP c/o cough and generalized fatigue x 3 months; ECOG PS 1
Initial CXR reveals a LUL opacity; follow-up CT of the chest reveals a 4-cm lobulated LUL mass
with associated L hilar and mediastinal LAD
She underwent a bronchoscopy and biopsy that revealed the diagnosis of SCLC
MRI brain is negative; PET/CT showed multiple FDG avid hepatic hypodensities and extensive
bone marrow uptake c/w skeletal metastasis
She is presenting to your medical oncology clinic to discuss further management
PeerView.com/HXN827 Copyright © 2000-2024, PeerView
Expert Panel Discussion
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Clinical and Research Accelerator
Can We Expand the Benefits
of Immunotherapy to LS-SCLC?
Professor Byoung Chul Cho, MD, PhD ee yy
Professor, Division of Medical Oncology z
Yonsei Cancer Center
Yonsei University College of Medicine -
Seoul, South Korea 4 2
Copyright © 2000-2024, Peerview
Can We Expand the Benefits
of Immunotherapy to LS-SCLC?
Professor Byoung Chul Cho, MD, PhD ee yy
Professor, Division of Medical Oncology z
Yonsei Cancer Center
Yonsei University College of Medicine -
Seoul, South Korea 4 2
Copyright © 2000-2024, Peerview
Another Case to Consider
72-year-old woman is diagnosed with LS-SCLC
She has a history of hypertension, COPD, and presents with cough and worsening
shortness of breath for 2 weeks
CT chest shows bulky right-sided mediastinal adenopathy
Additional staging with PET-CT and brain MRI show no evidence of metastatic disease
Copyright © 2000-2024, PeerView
72-year-old woman is diagnosed with LS-SCLC
She has a history of hypertension, COPD, and presents with cough and worsening
shortness of breath for 2 weeks
CT chest shows bulky right-sided mediastinal adenopathy
Additional staging with PET-CT and brain MRI show no evidence of metastatic disease
Copyright © 2000-2024, PeerView
Where Do We Go Next With Immunotherapies in SCLC?
Can adding radiation to immunotherapy help improve
Can we expand the benefits of immunsiherapy, to LS-SCLC?
Trials starting to answer these questions now...
PeerView.com
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Can adding radiation to immunotherapy help improve
Can we expand the benefits of immunsiherapy, to LS-SCLC?
Trials starting to answer these questions now...
PeerView.com
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Current Standard of Care and Unmet Needs in LS-SCLC‘?2
Limited-Stage Disease
ige for treatment of curative intent
71-2, NO, MO 74-2, M, MO
Td, Nx, MO + LS-SCLC (stage II) is
classified as SCLC that is
generally only in one lung
STAGE Bac or one side of the chest
accounts for approximately
30% of SCLC diagnoses
+ Prognosis remains poor
for patients with LS-SCLC
despite curative-intent
treatment with standard-of-
care cCRT: only 15%-30%
of patients are alive
5 years after diagnosis,
} ADRIATIC (Ourvalumab consoldation v placebo)?
À imo: 559 ve 334 mo
mission (ALL Sta
1. NCCN Cinical Practice Guidelines in Oncology. Small Cel Lung Cancer. Version 22024. tp uw nen orpprtessonals/pryicin, pce pa Ae
2 Bebb 0G etal. Pu Tor. 20239435480. PeerView.com
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Limited-Stage Disease
ige for treatment of curative intent
71-2, NO, MO 74-2, M, MO
Td, Nx, MO + LS-SCLC (stage II) is
classified as SCLC that is
generally only in one lung
STAGE Bac or one side of the chest
accounts for approximately
30% of SCLC diagnoses
+ Prognosis remains poor
for patients with LS-SCLC
despite curative-intent
treatment with standard-of-
care cCRT: only 15%-30%
of patients are alive
5 years after diagnosis,
} ADRIATIC (Ourvalumab consoldation v placebo)?
À imo: 559 ve 334 mo
mission (ALL Sta
1. NCCN Cinical Practice Guidelines in Oncology. Small Cel Lung Cancer. Version 22024. tp uw nen orpprtessonals/pryicin, pce pa Ae
2 Bebb 0G etal. Pu Tor. 20239435480. PeerView.com
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ADRIATIC: Durvalumab or Durvalumab + Tremelimumab
as Consolidation Treatment in LS-SCLC'
Phase 3, randomized, double-blind, placebo-controlled, multicenter study for patients with LS-SCLC
(inclusion criteria
+ Stage I-III LS-SCLC (stage III
inoperable)
I" PCI? permitted before randomization
Stratified by
+ Stage (Wil vs un)
_PCI (yes or no)
(CCRT components
Four cycles of platinum and
etoposide (three permitted?)
RT: 60-66 Gy QD over 6 wk or 45 Gy
BID over 3 wk
RT must commence no later than end
of cycle 2 of CT
‘CCRT and PCI treatment received per local standard of care, must be completed within 1 to 42d before randomization. disease contol was achieved and no
‘expected with an additonal cyte of chemotherapy. nthe opinion of the investigator.‘ The frs 600 patents were randomized 1:1:1 rai tothe thee treatment arms
‘andomized 1:1 to either durvalumab or placebo
1-Spigel DR etal ASCO 2024. Abstract LBAS.
PeerView.com/HXN827
without disease progression after cCRT
Durvalumab 1,500 mg
(n = 264)
urvalumab 1,51
Q4W for four doses
ed by durvalumab 1
(n = 200)
mg + tremelimumat
Treatment until investigator-determined progression or
intolerable toxicity, or a maximum of 24 mo
‘Dual primary endpoints
+ Durvalumab vs placebo
- 0s
— PFS (by BICR, per RECIST
v1.1)
Key secondary endpoints
+ Durvalumab + tremelimumab vs
placebo
- 08
— PFS (by BICR, per RECIST
vit)
Other secondary endpoints
+ OSIPFS landmarks
PeerView.com
Copyright © 2000-2024, PeerView
as Consolidation Treatment in LS-SCLC'
Phase 3, randomized, double-blind, placebo-controlled, multicenter study for patients with LS-SCLC
(inclusion criteria
+ Stage I-III LS-SCLC (stage III
inoperable)
I" PCI? permitted before randomization
Stratified by
+ Stage (Wil vs un)
_PCI (yes or no)
(CCRT components
Four cycles of platinum and
etoposide (three permitted?)
RT: 60-66 Gy QD over 6 wk or 45 Gy
BID over 3 wk
RT must commence no later than end
of cycle 2 of CT
‘CCRT and PCI treatment received per local standard of care, must be completed within 1 to 42d before randomization. disease contol was achieved and no
‘expected with an additonal cyte of chemotherapy. nthe opinion of the investigator.‘ The frs 600 patents were randomized 1:1:1 rai tothe thee treatment arms
‘andomized 1:1 to either durvalumab or placebo
1-Spigel DR etal ASCO 2024. Abstract LBAS.
PeerView.com/HXN827
without disease progression after cCRT
Durvalumab 1,500 mg
(n = 264)
urvalumab 1,51
Q4W for four doses
ed by durvalumab 1
(n = 200)
mg + tremelimumat
Treatment until investigator-determined progression or
intolerable toxicity, or a maximum of 24 mo
‘Dual primary endpoints
+ Durvalumab vs placebo
- 0s
— PFS (by BICR, per RECIST
v1.1)
Key secondary endpoints
+ Durvalumab + tremelimumab vs
placebo
- 08
— PFS (by BICR, per RECIST
vit)
Other secondary endpoints
+ OSIPFS landmarks
PeerView.com
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ADRIATIC: OS (Dual Primary Endpoint)!
+ Median duration of follow up in censored patients: 37.2 months (range 0.1-60.9)
10 Durvalum:
(n
)
Events, n (%) 115 (43.6) )
ig 08 MOS, mo (95% Cl) 55.9(37.3-NE) _ 33.4(25.9-39.9)
2 HR (85% Cl) 0.73 (0.57-0.93)
3 P 0104
3 06
2
Eos Din
E lacebo
02
o +
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63
Time, mo
No atRisk
Dunalumab 264 261 248 26 229 207 180 183 172 162 141 110 90 68 51 29 27 19 1 5 1 ©
Placebo 266 260 247 231 214 195 175 164 151 143 123 97 80 62 4% 3 23 19 8 5 1 0
+ OS was analyzed using a stratified log-rank test adjusted for receipt of PCI (yes vs no); the significance level for testing OS at this interim
analysis was 0.01679 (2-sided) at the overall 4.5% level, allowing for strong alpha control across interim and final analysis timepoints
1. Spigel DR etal ASCO 2024, Abstract LAS PeerView.com
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+ Median duration of follow up in censored patients: 37.2 months (range 0.1-60.9)
10 Durvalum:
(n
)
Events, n (%) 115 (43.6) )
ig 08 MOS, mo (95% Cl) 55.9(37.3-NE) _ 33.4(25.9-39.9)
2 HR (85% Cl) 0.73 (0.57-0.93)
3 P 0104
3 06
2
Eos Din
E lacebo
02
o +
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63
Time, mo
No atRisk
Dunalumab 264 261 248 26 229 207 180 183 172 162 141 110 90 68 51 29 27 19 1 5 1 ©
Placebo 266 260 247 231 214 195 175 164 151 143 123 97 80 62 4% 3 23 19 8 5 1 0
+ OS was analyzed using a stratified log-rank test adjusted for receipt of PCI (yes vs no); the significance level for testing OS at this interim
analysis was 0.01679 (2-sided) at the overall 4.5% level, allowing for strong alpha control across interim and final analysis timepoints
1. Spigel DR etal ASCO 2024, Abstract LAS PeerView.com
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ADRIATIC: OS Subgroup Analysis!
Al patents
Agey
WHO performance status
AICC disease stage
at diagnosis
Time from end of CORTE
te randomization, à
Por chemotherapy regimen
Prot radiation schedule
Best response to prior CRT
Prog PGI
gee-of Hf Exe
21410 28
Cisplatn-toposice
‘Once day
Twice dally
Partal response
Stable disease
No
Events/Pationts, uN
Ourvalumab
115264
sanso
40104
rane
366
gortso
sanar
48133
ernst
1109
1047291
1902
3770
ans
3181
danza
sanos
230
1291
senor
1542
suraz
enna
Placebo
146260
3162
63104
108188
3878
mar
sanzı
anat
Tas
1204
1947232
2462
sus
Tune
4688
10078
10787
3979
1504
116200
1582
eras
Tons
HR (85% cr,
073 057083)
076 0551.09)
070 048-102)
070 (052083)
083 (052-131)
0.75 (053-405)
072 (0501.04)
055 (038.079)
0.96 067-131)
0820040211)
071 (055091)
047 (024091)
0.0 (038.090)
080 (0641.27)
056 (0350.29)
082 081-1.10)
07205505)
088 (0401.14)
080 041.182)
076 (57-100)
054 0251.13)
075 (052-107)
071 (051-099)
0% 08 10 20
A
Favors durvalumab Favors placebo
Intentiontotreat analysis strated, subgroup analyses unstated. Not all respected subgroups are included inthe plot.
Size of exci is proporional to numberof events across bath arms.
* End of enemotherapy or rachtherapy, whichever was lates.
1-Spigel DR etal ASCO 2024. Abstract LBAS.
PeerView.com/HXN827
PeerView.com
Copyright © 2000-2024, PeerView
Al patents
Agey
WHO performance status
AICC disease stage
at diagnosis
Time from end of CORTE
te randomization, à
Por chemotherapy regimen
Prot radiation schedule
Best response to prior CRT
Prog PGI
gee-of Hf Exe
21410 28
Cisplatn-toposice
‘Once day
Twice dally
Partal response
Stable disease
No
Events/Pationts, uN
Ourvalumab
115264
sanso
40104
rane
366
gortso
sanar
48133
ernst
1109
1047291
1902
3770
ans
3181
danza
sanos
230
1291
senor
1542
suraz
enna
Placebo
146260
3162
63104
108188
3878
mar
sanzı
anat
Tas
1204
1947232
2462
sus
Tune
4688
10078
10787
3979
1504
116200
1582
eras
Tons
HR (85% cr,
073 057083)
076 0551.09)
070 048-102)
070 (052083)
083 (052-131)
0.75 (053-405)
072 (0501.04)
055 (038.079)
0.96 067-131)
0820040211)
071 (055091)
047 (024091)
0.0 (038.090)
080 (0641.27)
056 (0350.29)
082 081-1.10)
07205505)
088 (0401.14)
080 041.182)
076 (57-100)
054 0251.13)
075 (052-107)
071 (051-099)
0% 08 10 20
A
Favors durvalumab Favors placebo
Intentiontotreat analysis strated, subgroup analyses unstated. Not all respected subgroups are included inthe plot.
Size of exci is proporional to numberof events across bath arms.
* End of enemotherapy or rachtherapy, whichever was lates.
1-Spigel DR etal ASCO 2024. Abstract LBAS.
PeerView.com/HXN827
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ADRIATIC: PFS? (Dual Primary Endpoint)’
+ Median duration of follow up in censored patients: 27.6 months (range 0.0-55.8)
10
we vents, n (%) )
MOS, mo (25% Cl) 166(10.2-282) 92(74-129)
2 HR (95% CI) 0.76 (0.61-0.95)
3 06 nn | A
8
4
Ê 04
es Durvalumab
Placebo
& 02
o + +
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63
Time, mo
No, at Risk
Durvalumad 264 212 161 135 113 105 101 98 84 78 St 51 33 21 19 10 10 4 4 0 0 0
Placebo 266 208 146 122 100 88 79 76 71 OO 47 47 34 23 22 15 14 5 5 0 0 0
By BICR per RECIST v1.1. PFS was analyzed using a srl log rank test adjusted for disease stage (UI v I) and receipt of PCI yes v no). Th signicance
level for testing PFS at his interim analysis was 0.00184 (2-sded) at the 0.5% level, and 0.02605 (eis) atthe overal 5% level. Statistical igicance for PFS was
“achieved though the recycing mule testing procedure framework and testing atthe 5% (2-sded) alpha level (agiusted for an interim and final analysis). a
Y Spigel DR etal ASCO 2024, Abstract LBAS PeerView.com
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+ Median duration of follow up in censored patients: 27.6 months (range 0.0-55.8)
10
we vents, n (%) )
MOS, mo (25% Cl) 166(10.2-282) 92(74-129)
2 HR (95% CI) 0.76 (0.61-0.95)
3 06 nn | A
8
4
Ê 04
es Durvalumab
Placebo
& 02
o + +
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63
Time, mo
No, at Risk
Durvalumad 264 212 161 135 113 105 101 98 84 78 St 51 33 21 19 10 10 4 4 0 0 0
Placebo 266 208 146 122 100 88 79 76 71 OO 47 47 34 23 22 15 14 5 5 0 0 0
By BICR per RECIST v1.1. PFS was analyzed using a srl log rank test adjusted for disease stage (UI v I) and receipt of PCI yes v no). Th signicance
level for testing PFS at his interim analysis was 0.00184 (2-sded) at the 0.5% level, and 0.02605 (eis) atthe overal 5% level. Statistical igicance for PFS was
“achieved though the recycing mule testing procedure framework and testing atthe 5% (2-sded) alpha level (agiusted for an interim and final analysis). a
Y Spigel DR etal ASCO 2024, Abstract LBAS PeerView.com
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ADRIATIC: PFS Subgroup Analysis!
Aupatens
ney S
tite
in Female
une
Race wo
WO peromance sais °
ICO seas tage u
agree '"
su
Time tom end oR
manten à a
Canopainetponce
Prercnemsteranyegimen opin
vicki st ‘nce day
a Twice daily
Compt response
esresponse opor CRT anal vsprse
Sie osea
ver
Prerpoi ve
Evonts/Patints, uN
Durvalumab
139264
831160
senos
re
4306
657190
Test
sons
Test
1483
125231
1802
4379
Tensa
4491
95/173
108/105,
31169
3501
108191
1842
ssnaz
Tanza
Placebo
1097268
ganz
Tios
120188.
4078
Sonar
Tanzı
ass
Ss
12178
122187
4779
1804
130200
2032
ans
ass
HR (95% ch
076 (081-085)
0.77 058-103)
0.77 (0541.10)
0.80 (061-104)
071 (047-108)
068 (040063)
0.91 (006-120)
0.64 046.090)
0.91 (067-124)
071 035-142)
077 (061-008)
045 (0.24083)
0.09 059-124)
079 (058107)
081 (041-060)
088 (851.18)
0.77 (060-100)
0.72 (045-1.13)
1.00 0.0.1.90)
081 082.109)
050 026-054)
0.73 (053101)
0.80 (030-100)
COS y 2
I 5
Favors durvalumab Favors placebo
Intentonto-treat analysis stratified, subgroup analyses unstated. Not all prespeciied subgroups ar included in the plot
‘Size of erde is proportional to number of events across both arms.
End of chemotherapy or rachtherapy, whichever was latest
1-Spigel DR etal ASCO 2024. Abstract LBAS.
PeerView.com/HXN827
PeerView.com
Copyright © 2000-2024, PeerView
Aupatens
ney S
tite
in Female
une
Race wo
WO peromance sais °
ICO seas tage u
agree '"
su
Time tom end oR
manten à a
Canopainetponce
Prercnemsteranyegimen opin
vicki st ‘nce day
a Twice daily
Compt response
esresponse opor CRT anal vsprse
Sie osea
ver
Prerpoi ve
Evonts/Patints, uN
Durvalumab
139264
831160
senos
re
4306
657190
Test
sons
Test
1483
125231
1802
4379
Tensa
4491
95/173
108/105,
31169
3501
108191
1842
ssnaz
Tanza
Placebo
1097268
ganz
Tios
120188.
4078
Sonar
Tanzı
ass
Ss
12178
122187
4779
1804
130200
2032
ans
ass
HR (95% ch
076 (081-085)
0.77 058-103)
0.77 (0541.10)
0.80 (061-104)
071 (047-108)
068 (040063)
0.91 (006-120)
0.64 046.090)
0.91 (067-124)
071 035-142)
077 (061-008)
045 (0.24083)
0.09 059-124)
079 (058107)
081 (041-060)
088 (851.18)
0.77 (060-100)
0.72 (045-1.13)
1.00 0.0.1.90)
081 082.109)
050 026-054)
0.73 (053101)
0.80 (030-100)
COS y 2
I 5
Favors durvalumab Favors placebo
Intentonto-treat analysis stratified, subgroup analyses unstated. Not all prespeciied subgroups ar included in the plot
‘Size of erde is proportional to number of events across both arms.
End of chemotherapy or rachtherapy, whichever was latest
1-Spigel DR etal ASCO 2024. Abstract LBAS.
PeerView.com/HXN827
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ADRIATIC: Exposure and Safety Summary!
Durvalumab Placebo
di 62) (n
Median (range) 9 (1-26) 9 (1-26)
Durvalumab or placebo doses, n
Mean (standard deviation) 129(9.5) — 11.8(9.2)
Any-grade all-cause AEs, n (%) 247 (94.3) 234 (88.3)
Maximum grade 3/4 AEs 64 (24.4) 64 (24.2)
Serious AEs 78 (29.8) 64(242)
AEs leading to treatment discontinuation 43(164) 28(106)
AEs leading to death zen 5(1.9)
Treatment-related* AEs leading to death 20.8" o
Any-grade immune-mediated AEs? 84 (321) 27(102)
Maximum grade 3/4 immune-mediated AES 14 (53) 4(15)
Includes AEs wi an onset ate folowing fst dose of study treatment. or pre-treatment AES that increased in severty folowing frst dose of study restment, through to 90 days ater last dose
‘cunt star ofthe first subsequent systemic anticancer therapy (whichever occures fr)
"Assessed by investgator.* Defined as an AE of special interest (excluding infusion relatedhypersensitviy/anaphyfactc reacton) that is consistent with an immune-mediated mechanism
‘that required treatment with systemic eoricosteroids, other mmunosuppressans, or endocrine therapy.‘ Causes ol death were encephalopathy and pneumonis. $
Y Spigel DR etal ASCO 2024. Abstract LAS PeerView.com
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Durvalumab Placebo
di 62) (n
Median (range) 9 (1-26) 9 (1-26)
Durvalumab or placebo doses, n
Mean (standard deviation) 129(9.5) — 11.8(9.2)
Any-grade all-cause AEs, n (%) 247 (94.3) 234 (88.3)
Maximum grade 3/4 AEs 64 (24.4) 64 (24.2)
Serious AEs 78 (29.8) 64(242)
AEs leading to treatment discontinuation 43(164) 28(106)
AEs leading to death zen 5(1.9)
Treatment-related* AEs leading to death 20.8" o
Any-grade immune-mediated AEs? 84 (321) 27(102)
Maximum grade 3/4 immune-mediated AES 14 (53) 4(15)
Includes AEs wi an onset ate folowing fst dose of study treatment. or pre-treatment AES that increased in severty folowing frst dose of study restment, through to 90 days ater last dose
‘cunt star ofthe first subsequent systemic anticancer therapy (whichever occures fr)
"Assessed by investgator.* Defined as an AE of special interest (excluding infusion relatedhypersensitviy/anaphyfactc reacton) that is consistent with an immune-mediated mechanism
‘that required treatment with systemic eoricosteroids, other mmunosuppressans, or endocrine therapy.‘ Causes ol death were encephalopathy and pneumonis. $
Y Spigel DR etal ASCO 2024. Abstract LAS PeerView.com
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ADRIATIC: Most Frequent AEs‘?
Maximum grade: MM 1/2 23 Duralumab 1/2 23 Placebo
Radiation pneumoitis 29 234
Decreased appetite
Hypothyroidism
Cough
Pruritus
Nausea
Dizziness
Fatigue
Diarrhea
Pneumonia
Pneumonitis
Rash
Constipation
Hyperthyroidism
Headache
Arthralgía 109
40 30 20 10 0 10 20 30 40
Durvalumab (n = 262) Patients, % Placebo (n = 265)
Preferred Term
* Occuring in 210% of patents in ether treatment arm. .
1"Spige BR et at ASCO 2024 Abstract BAS PeerView.com
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Maximum grade: MM 1/2 23 Duralumab 1/2 23 Placebo
Radiation pneumoitis 29 234
Decreased appetite
Hypothyroidism
Cough
Pruritus
Nausea
Dizziness
Fatigue
Diarrhea
Pneumonia
Pneumonitis
Rash
Constipation
Hyperthyroidism
Headache
Arthralgía 109
40 30 20 10 0 10 20 30 40
Durvalumab (n = 262) Patients, % Placebo (n = 265)
Preferred Term
* Occuring in 210% of patents in ether treatment arm. .
1"Spige BR et at ASCO 2024 Abstract BAS PeerView.com
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ADRIATIC: Conclusions!
+ Durvalumab as consolidation treatment after cCCRT demonstrated statistically significant and clinically
meaningful improvement in OS and PFS compared with placebo in patients with LS-SCLC
— OS HR 0.73 (95% Cl 0.57-0.93), P = .0104; mOS 55.9 (95% Cl 37.3-NE) vs
33.4 (95% Cl 25.5-39.9) months
— PFS HR 0.76 (95% Cl 0.61-0.95), P = .0161; mPFS 16.6 (95% Cl 10.2-28.2) vs
9.2 (95% Cl 7.4-12.9) months
— Treatment benefit was generally consistent across predefined patient subgroups for both OS and PFS
+ Durvalumab consolidation treatment for up to 2 years was well tolerated, and safety findings were consistent
with the known safety profile of durvalumab monotherapy in the post-cCRT setting
These data support consolidation durvalumab as a new standard of care
for patients with LS-SCLC who have not progressed after CCRT
1. Spigel DR et al ASCO 2024. Abstract LBAS. PeerView.com
PeerView.com/HXN827 Copyright © 2000-2024, PeerView
+ Durvalumab as consolidation treatment after cCCRT demonstrated statistically significant and clinically
meaningful improvement in OS and PFS compared with placebo in patients with LS-SCLC
— OS HR 0.73 (95% Cl 0.57-0.93), P = .0104; mOS 55.9 (95% Cl 37.3-NE) vs
33.4 (95% Cl 25.5-39.9) months
— PFS HR 0.76 (95% Cl 0.61-0.95), P = .0161; mPFS 16.6 (95% Cl 10.2-28.2) vs
9.2 (95% Cl 7.4-12.9) months
— Treatment benefit was generally consistent across predefined patient subgroups for both OS and PFS
+ Durvalumab consolidation treatment for up to 2 years was well tolerated, and safety findings were consistent
with the known safety profile of durvalumab monotherapy in the post-cCRT setting
These data support consolidation durvalumab as a new standard of care
for patients with LS-SCLC who have not progressed after CCRT
1. Spigel DR et al ASCO 2024. Abstract LBAS. PeerView.com
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NRG/Alliance LU005: cCRT + Atezolizumab in LS-SCLC!
Phase 2/3, randomized study of cCRT + Atezolizumab in LS-SCLC
Patient population Platinum*/etoposide x 4 cycles
+ LS-SCLC
Pallonta mel have received thoracic RT 45 Gy BID or 6
1 cycle of platinum/etoposide prior daily beginning + Primary endpoints: PFS
to registration ° 2 (phase 2), OS (phase 3)
+ Measurable disease
le + Secondary endpoints: ORR,
Stratified by local and distant disease
Radiation schedule (BID vs daily) cic RT 4! BID or 66 G control, QOUPRO
Chemotherapy (cisplatin vs daily beginning with cycle 2
carboplatin) chemotherapy”
‘Sex (male vs female)
ECOG (0/1 vs 2)
Fist ele of chematherapy must be given piro study entry fr atta of 4 eyes, 3 given on study. Chemotherapy doubts delivered concurenty, cisplatnetoposide o carboplatin etoposide
8 required. The steinvestgal must deciae the chemotherapy regimen that the pabent wil receive prior to the patent’ randomization Patents who develop a contrandicatn 1 cisplatin afer
Beginning therapy may receive carboplatin in subsequent cycle. Al pabents vih a complete or near compiete response ae svongly recommended to receveproprylact canal kradiaton (PC).
planned within 4 10 6 weeks from completion of chemoradionerapy. Significant chemoradictherapy toxicives shouldbe resolved to grade 2 ar less before beginning PCI. Patents in arm 2 uno
Teceve PCI wil ceive concurrent with tezokzumab, a
{Higgins KA etal WCLC 2020 poster P48.02. PeerView.com
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Phase 2/3, randomized study of cCRT + Atezolizumab in LS-SCLC
Patient population Platinum*/etoposide x 4 cycles
+ LS-SCLC
Pallonta mel have received thoracic RT 45 Gy BID or 6
1 cycle of platinum/etoposide prior daily beginning + Primary endpoints: PFS
to registration ° 2 (phase 2), OS (phase 3)
+ Measurable disease
le + Secondary endpoints: ORR,
Stratified by local and distant disease
Radiation schedule (BID vs daily) cic RT 4! BID or 66 G control, QOUPRO
Chemotherapy (cisplatin vs daily beginning with cycle 2
carboplatin) chemotherapy”
‘Sex (male vs female)
ECOG (0/1 vs 2)
Fist ele of chematherapy must be given piro study entry fr atta of 4 eyes, 3 given on study. Chemotherapy doubts delivered concurenty, cisplatnetoposide o carboplatin etoposide
8 required. The steinvestgal must deciae the chemotherapy regimen that the pabent wil receive prior to the patent’ randomization Patents who develop a contrandicatn 1 cisplatin afer
Beginning therapy may receive carboplatin in subsequent cycle. Al pabents vih a complete or near compiete response ae svongly recommended to receveproprylact canal kradiaton (PC).
planned within 4 10 6 weeks from completion of chemoradionerapy. Significant chemoradictherapy toxicives shouldbe resolved to grade 2 ar less before beginning PCI. Patents in arm 2 uno
Teceve PCI wil ceive concurrent with tezokzumab, a
{Higgins KA etal WCLC 2020 poster P48.02. PeerView.com
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Combinations of RT and Immunotherapy
and Other Investigational Strategies in LS-SCLC12
Stratified
pare by BID and
CCRT + atezolizumab followed ‘QD RT Primary
by atezolizumab consolidation by atezo Q3W x14 cycles (10.5 mo) MEA eau
LU-005 21 days after first CTX dose "os
Phase 3 (+14 days if not recovered) He
9 ECOG PS 0-2 EP x3 cycles concurrent with RT
5 RT schedule stratification
& Straliled followed by pembro Q6W
9 x9 cycles (13.5 mi
+ Double-blind, placebo-controlled Be eet à Primary.
& CORTS pembxoltauniab tolowed Pembro + EP (Q3W + 4 cycles)+ endpoints
SS dy pembrolizumab + olaparib RT followed by pembroQcw + PFS and
Phi 'consoldallon x9 cycles (13.5 mo) + olaparib os
an stratification n= 672 300 mg x12 mo
1. tps lenicatils govstucyNCTO3811002. 2 htps/ieincatals. gowstudyINCTO4624204. PeerView.com
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and Other Investigational Strategies in LS-SCLC12
Stratified
pare by BID and
CCRT + atezolizumab followed ‘QD RT Primary
by atezolizumab consolidation by atezo Q3W x14 cycles (10.5 mo) MEA eau
LU-005 21 days after first CTX dose "os
Phase 3 (+14 days if not recovered) He
9 ECOG PS 0-2 EP x3 cycles concurrent with RT
5 RT schedule stratification
& Straliled followed by pembro Q6W
9 x9 cycles (13.5 mi
+ Double-blind, placebo-controlled Be eet à Primary.
& CORTS pembxoltauniab tolowed Pembro + EP (Q3W + 4 cycles)+ endpoints
SS dy pembrolizumab + olaparib RT followed by pembroQcw + PFS and
Phi 'consoldallon x9 cycles (13.5 mo) + olaparib os
an stratification n= 672 300 mg x12 mo
1. tps lenicatils govstucyNCTO3811002. 2 htps/ieincatals. gowstudyINCTO4624204. PeerView.com
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Phase 3 Study of Tarlatamab (AMG 757) in LS-SCLC
That Has Not Progressed After cCRT!
3s
«Staite by: ropinlacte canal rado (PO) ease sage, and number of els a chema rr to enrmen, > Subjects wi civ sy ram
tox, withdrawal death, or fora maximum of 12 months (whichever occurs rs) © Subjects wil receive 1 mg
Se ee ony yore vo tras Jon on any ar e ran GW rt Placebo. ‘Schedule wil match
{arlatamab schedule. End of treatment vist wl occur at the time the decision is made to discontinue within 14 days ater last dose of
veneran prt sal o acres erp ve De tra oe fs ame a
1. hips /einieatias gov'studyINCTO6117774 PeerView.com
Tarlatamab 10 mg Q2W><
n= 200
=>
End of treatment
Placebo Q2W+
n=200
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That Has Not Progressed After cCRT!
3s
«Staite by: ropinlacte canal rado (PO) ease sage, and number of els a chema rr to enrmen, > Subjects wi civ sy ram
tox, withdrawal death, or fora maximum of 12 months (whichever occurs rs) © Subjects wil receive 1 mg
Se ee ony yore vo tras Jon on any ar e ran GW rt Placebo. ‘Schedule wil match
{arlatamab schedule. End of treatment vist wl occur at the time the decision is made to discontinue within 14 days ater last dose of
veneran prt sal o acres erp ve De tra oe fs ame a
1. hips /einieatias gov'studyINCTO6117774 PeerView.com
Tarlatamab 10 mg Q2W><
n= 200
=>
End of treatment
Placebo Q2W+
n=200
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NRG LU007/RAPTOR: Consolidation Radiation +
Atezolizumab in ES-SCLC*
Phase 2/3, randomized study of consolidation radiation + immunotherapy for ES-SCLC
Patient population: = >
+ Primary endpoints:
+ ES-SCLC Atezolizumab maintenance investigator-assessed PFS
+ SD or PR after 4-6 cycles of (plane 2/07 OS Chess)
etoposide/platinum doublet plus
atezolizumab + Secondary endpoints: toxicity,
rn PFS (phase 3), PFS and OS in
Stratified by: patients with 1-3 visible tumors
+ Number of sites receiving radiation u and >3 visible tumors, and PFS
therapy (field 1-3 vs >3) hora 45 Gy and OS in patients receiving
+ SDvsPR ‘complete consolidation* and
+ ECOG (0/1 vs 2) : patients who receive incomplete
a consolidation?
Patents reingconskdatonradterapy 1 al able dns. Patents o dono recive consoldation radiation to al vse dense. ñ
1. ps in inialals govstudy/NCTO4402788 PeerView.com
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Atezolizumab in ES-SCLC*
Phase 2/3, randomized study of consolidation radiation + immunotherapy for ES-SCLC
Patient population: = >
+ Primary endpoints:
+ ES-SCLC Atezolizumab maintenance investigator-assessed PFS
+ SD or PR after 4-6 cycles of (plane 2/07 OS Chess)
etoposide/platinum doublet plus
atezolizumab + Secondary endpoints: toxicity,
rn PFS (phase 3), PFS and OS in
Stratified by: patients with 1-3 visible tumors
+ Number of sites receiving radiation u and >3 visible tumors, and PFS
therapy (field 1-3 vs >3) hora 45 Gy and OS in patients receiving
+ SDvsPR ‘complete consolidation* and
+ ECOG (0/1 vs 2) : patients who receive incomplete
a consolidation?
Patents reingconskdatonradterapy 1 al able dns. Patents o dono recive consoldation radiation to al vse dense. ñ
1. ps in inialals govstudy/NCTO4402788 PeerView.com
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TREASURE: Thoracic Radiotherapy With Atezolizumab
in Small Cell Lung Cancer Extensive Disease’
Study Design
10x3Gy
in 10 days
Key Inclusion Criteria
+ Ext. dis. SCLC
+ Any response after
induction therapy with 4 x
Thoracic radiotherapy +
atezolizumab
maintenance
Stratification
+ Presence of brain
carboplatin/etoposide + metastases (yes
atezolizumab vs no) = ed
+ ECOG 0 or 1 + Thoracic response Toxicity (pneumonitis 2 grade 3)
Key Exclusion Criteria ‘after induction Atezolizumab
+ PD after induction therapy Eo maintenance
+ Autoimmune disease =)
in + PCI (yes vs no)
+ ED SCLC patients after four cycles of standard chemo-immunotherapy (carboplatin, etoposide, atezolizumab) with any
response, defined as CR/PR or thoracic SD with CR/PR of extrathoracio lesions, are included into the study and
randomized into a group that receives thoracic radiotherapy or one that does not
+ All patients will receive maintenance atezolizumab treatment until disease progression or the occurrence of toxic effect
* Safety interim analysis in arm A ater n= 23 patients, Safety signal 22 patients wih 23 pneumonitis :
1. Bozorgmehr F et al ESMO 2023. Abstract 1980M0. PeerView.com
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in Small Cell Lung Cancer Extensive Disease’
Study Design
10x3Gy
in 10 days
Key Inclusion Criteria
+ Ext. dis. SCLC
+ Any response after
induction therapy with 4 x
Thoracic radiotherapy +
atezolizumab
maintenance
Stratification
+ Presence of brain
carboplatin/etoposide + metastases (yes
atezolizumab vs no) = ed
+ ECOG 0 or 1 + Thoracic response Toxicity (pneumonitis 2 grade 3)
Key Exclusion Criteria ‘after induction Atezolizumab
+ PD after induction therapy Eo maintenance
+ Autoimmune disease =)
in + PCI (yes vs no)
+ ED SCLC patients after four cycles of standard chemo-immunotherapy (carboplatin, etoposide, atezolizumab) with any
response, defined as CR/PR or thoracic SD with CR/PR of extrathoracio lesions, are included into the study and
randomized into a group that receives thoracic radiotherapy or one that does not
+ All patients will receive maintenance atezolizumab treatment until disease progression or the occurrence of toxic effect
* Safety interim analysis in arm A ater n= 23 patients, Safety signal 22 patients wih 23 pneumonitis :
1. Bozorgmehr F et al ESMO 2023. Abstract 1980M0. PeerView.com
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TREASURE: Safety!
+ During routine SMC safety review in Q3-2022 — identification of potential imbalance in the total number of fatal SAEs
in armA (5 vs 1)
Due to this imbalance — ad hoc unplanned interim OS analysis — led SMC to propose stopping recruitment for three months;
results were not shared with Cl and the sponsor but only with the SMC to ensure the integrity of the study
in arm A (6 vs 1)
‘Any grade AES 166 (62)
Grade 3-4 28 (78)
Grade 5 6 (66)
Leading to disc:
atezolizumab 560)
Leading to dise,
Led 2(100)
Any grade
trealment-related AE 569
‘Thereof SAES 28 (76)
1. Bozorgmehr F et al ESMO 2023, Abstract 1988M0.
PeerView.com/HXN827
Arm B: Atezo, n
Total, N
266 (100)
36 (100)
7 (100)
16 (100)
2(100)
102 (100)
37 (100)
Re-analysis 11/2022 — no change in OS, a three-times higher number of SAEs in arm A, increased number of fatal SAEs
Death of death in arm A
Sepsis: ulcus cruris with staph. aureus sepsis
Sepsis: pneumonia DD urosepsis (pseudomonas)
Multiorgan failure (patient found dead at home)
Lung infection (febrile infection with cough)
Pneumonitis (pre-existing ILD)
Worsening of general condition (PD was missed)
Cause of death in arm B
Hepatic failure (irHepatitis and irNephritis)
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+ During routine SMC safety review in Q3-2022 — identification of potential imbalance in the total number of fatal SAEs
in armA (5 vs 1)
Due to this imbalance — ad hoc unplanned interim OS analysis — led SMC to propose stopping recruitment for three months;
results were not shared with Cl and the sponsor but only with the SMC to ensure the integrity of the study
in arm A (6 vs 1)
‘Any grade AES 166 (62)
Grade 3-4 28 (78)
Grade 5 6 (66)
Leading to disc:
atezolizumab 560)
Leading to dise,
Led 2(100)
Any grade
trealment-related AE 569
‘Thereof SAES 28 (76)
1. Bozorgmehr F et al ESMO 2023, Abstract 1988M0.
PeerView.com/HXN827
Arm B: Atezo, n
Total, N
266 (100)
36 (100)
7 (100)
16 (100)
2(100)
102 (100)
37 (100)
Re-analysis 11/2022 — no change in OS, a three-times higher number of SAEs in arm A, increased number of fatal SAEs
Death of death in arm A
Sepsis: ulcus cruris with staph. aureus sepsis
Sepsis: pneumonia DD urosepsis (pseudomonas)
Multiorgan failure (patient found dead at home)
Lung infection (febrile infection with cough)
Pneumonitis (pre-existing ILD)
Worsening of general condition (PD was missed)
Cause of death in arm B
Hepatic failure (irHepatitis and irNephritis)
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Coming Back to Our Case
72-year-old woman is diagnosed with LS-SCLC
She has a history of hypertension, COPD, and presents with cough and worsening
shortness of breath for 2 weeks
CT chest shows bulky right-sided mediastinal adenopathy
Additional staging with PET-CT and brain MRI show no evidence of metastatic disease
Copyright © 2000-2024, PeerView
72-year-old woman is diagnosed with LS-SCLC
She has a history of hypertension, COPD, and presents with cough and worsening
shortness of breath for 2 weeks
CT chest shows bulky right-sided mediastinal adenopathy
Additional staging with PET-CT and brain MRI show no evidence of metastatic disease
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Expert Panel Discussion
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Clinical and Research Accelerator
How Can We Make the Most of the
Established and New Second-Line and
Beyond Treatment Options for SCLC?
Carl M. Gay, MD, PhD
Assistant Professor
Department of Thoracic/Head and Neck Medical Oncology BE
Division of Cancer Medicine
The University of Texas MD Anderson Cancer Center
Houston, Texas
Copyright © 2000-2024,
How Can We Make the Most of the
Established and New Second-Line and
Beyond Treatment Options for SCLC?
Carl M. Gay, MD, PhD
Assistant Professor
Department of Thoracic/Head and Neck Medical Oncology BE
Division of Cancer Medicine
The University of Texas MD Anderson Cancer Center
Houston, Texas
Copyright © 2000-2024,
Another Case to Consider
An 80-year-old woman newly diagnosed with ES-SCLC received initial treatment with EP + durvalumab
She completed 4 cycles of induction chemoimmunotherapy with delays in initiating C3 and C4
because of delayed count recovery
She transitioned to durvalumab maintenance
Routine restaging CT scans after 7 cycles of Q4W maintenance durvalumab unfortunately
demonstrated multiple new or progressive hepatic lesions
MRI of brain shows 4 sub-centimeter parenchymal lesions consistent with metastases and
without perilesional edema
ECOG PS remains preserved, and she wants to explore other therapeutic options
PeerView.com/HXN827 Copyright © 2000-2024, PeerView
An 80-year-old woman newly diagnosed with ES-SCLC received initial treatment with EP + durvalumab
She completed 4 cycles of induction chemoimmunotherapy with delays in initiating C3 and C4
because of delayed count recovery
She transitioned to durvalumab maintenance
Routine restaging CT scans after 7 cycles of Q4W maintenance durvalumab unfortunately
demonstrated multiple new or progressive hepatic lesions
MRI of brain shows 4 sub-centimeter parenchymal lesions consistent with metastases and
without perilesional edema
ECOG PS remains preserved, and she wants to explore other therapeutic options
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Platinum Doublet Rechallenge vs Topotecan!
Median PFS, 27
mo(@0% CI) (2332)
HR (90% ci
100 HR (90% cn
75
x
‘a Combination
2
a
25
o
o 25 50 75
Time, mo
No. at Risk (Censored)
Topotecan 81 (0) 4500) 150) 20
Combination chemo 810) CTI 70) sa
1.Baize Net al. Lancet Oncol 2020:21:1224-1233.
PeerView.com/HXN827
6555
057 (0410.73)
‘boas
100
75 Combination chemo
x
chemo Pe
°
25
o
10.0 o 10 20 30 40
Time, mo
No, at Risk (Censored)
10) Topotecan 79 (0) 270) so 2@) 1@)
oa) Combination chemo 77 (0) 2500) co 0 0)
PeerView.com
Copyright © 2000-2024, Peerview
Median PFS, 27
mo(@0% CI) (2332)
HR (90% ci
100 HR (90% cn
75
x
‘a Combination
2
a
25
o
o 25 50 75
Time, mo
No. at Risk (Censored)
Topotecan 81 (0) 4500) 150) 20
Combination chemo 810) CTI 70) sa
1.Baize Net al. Lancet Oncol 2020:21:1224-1233.
PeerView.com/HXN827
6555
057 (0410.73)
‘boas
100
75 Combination chemo
x
chemo Pe
°
25
o
10.0 o 10 20 30 40
Time, mo
No, at Risk (Censored)
10) Topotecan 79 (0) 270) so 2@) 1@)
oa) Combination chemo 77 (0) 2500) co 0 0)
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Topotecan Efficacy’?
+ Topotecan 2.3 mg/m?/d PO for days 1 to 5 every + Topotecan 1.5 mg/m?/d IV for days 1 to 5 every 21 days
A
21 days vs CAV
— Eligibility included chemotherapy-free — Eligibility included chemotherapy-free interval of
interval of at least 45 days after 1L therapy at least 60 days after 1L therapy
£
<
E
€
2
E
é
2
3
E
3
o
ÉRDETTETTITEITITETTITETITIE
Timo, wk Time, wk
1. O'Brien MER et al. Clin Oncol 2006:24:5441-5447.2. von Pawel Jt al Cin Oncol, 1999:17:658-667. PeerView.com
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+ Topotecan 2.3 mg/m?/d PO for days 1 to 5 every + Topotecan 1.5 mg/m?/d IV for days 1 to 5 every 21 days
A
21 days vs CAV
— Eligibility included chemotherapy-free — Eligibility included chemotherapy-free interval of
interval of at least 45 days after 1L therapy at least 60 days after 1L therapy
£
<
E
€
2
E
é
2
3
E
3
o
ÉRDETTETTITEITITETTITETITIE
Timo, wk Time, wk
1. O'Brien MER et al. Clin Oncol 2006:24:5441-5447.2. von Pawel Jt al Cin Oncol, 1999:17:658-667. PeerView.com
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Lurbinectedin: Rationale for Use in SCLC
as a Translationally Active Disease’
SCI
has genomic alterations
> rapid cell proliferation
+ TP53 mutation, RB1 loss
+ MYC amplification
Lurbinectedin )
+ Binds to DNA promoters > binding of
transcription factors prevented > oncogenic
transcription inhibited > cell apoptosis
1.Farrago AF et al. Future Oncology. 2019,15:231-230 PeerView.com
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as a Translationally Active Disease’
SCI
has genomic alterations
> rapid cell proliferation
+ TP53 mutation, RB1 loss
+ MYC amplification
Lurbinectedin )
+ Binds to DNA promoters > binding of
transcription factors prevented > oncogenic
transcription inhibited > cell apoptosis
1.Farrago AF et al. Future Oncology. 2019,15:231-230 PeerView.com
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Phase 2 Basket Trial of Lurbinectedin
as Single Agent in Second-Line SCLC’
Statistical Assumptions
for the SCLC Cohort
Null hypothesis: <15% get a
response (Ps.15)
+ Alternative hypothesis: 230%
get a response (P 2.30)
+ Statistical power: 95%
+ 223% of confirmed responses
needed to reject the null
hypothesis
Patients With SCLC
PS02
One prior chemotherapy ine | Lurbinectedin 3.2 mg/m 1-h IV GW
+ Prior immunotherapy
allowed
‘Adequate organ function
CNS mets excluded
investigator-assessed ORR by RECIST v1.1
Five contemed responses observed in the fst 15 treated patents :
1. Tigo Jet al Lancet Oneal. 02021:645.54, PeerView.com
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as Single Agent in Second-Line SCLC’
Statistical Assumptions
for the SCLC Cohort
Null hypothesis: <15% get a
response (Ps.15)
+ Alternative hypothesis: 230%
get a response (P 2.30)
+ Statistical power: 95%
+ 223% of confirmed responses
needed to reject the null
hypothesis
Patients With SCLC
PS02
One prior chemotherapy ine | Lurbinectedin 3.2 mg/m 1-h IV GW
+ Prior immunotherapy
allowed
‘Adequate organ function
CNS mets excluded
investigator-assessed ORR by RECIST v1.1
Five contemed responses observed in the fst 15 treated patents :
1. Tigo Jet al Lancet Oneal. 02021:645.54, PeerView.com
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Lurbinectedin: Efficacy’
Al Pationts Interval 904 Interval 280 d E E .
pa) (n=60) sm #2
RECT Response 8: gi
Compl reponse 0 o o 3 E
Est are wa aus el E
‘Stable disease, n (%)" 35 (33) 13 29) 22(37) Lt 3 we
E 2m wo vun © Tacomas à
cer) 26 20 10 pa den
Oran À (8% 0) Ba ae asogziseay Te en on
Dres (058 CI Men) use) OUEN) u
OR
Disease progression. elapse, or death
events in responding patients, rN (%) 20137 (78) 9110 80) 20027 (74)
‘Medan duration of response, mo (range) 534184) 470656) 928573)
Patients sil responding at 6 mo, % (range) 43.0 (256.05) 417033.) 55.3 (45760)
PES
PES events, n(%) 9080) so 49 (62)
Median PFS, mo (85% Ch) 352643) 281339) 460865)
mo PFS, % (05% Ci) 4660987565) 291(153428) S09(471-727)
320 233425) 188(68309 435(01-589)
68 (63) 37 (82) 28 (48)
93163118) 504.183) 119 (07-182)
7176787) 458(904813) 8367.05) EII RA
rom
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Al Pationts Interval 904 Interval 280 d E E .
pa) (n=60) sm #2
RECT Response 8: gi
Compl reponse 0 o o 3 E
Est are wa aus el E
‘Stable disease, n (%)" 35 (33) 13 29) 22(37) Lt 3 we
E 2m wo vun © Tacomas à
cer) 26 20 10 pa den
Oran À (8% 0) Ba ae asogziseay Te en on
Dres (058 CI Men) use) OUEN) u
OR
Disease progression. elapse, or death
events in responding patients, rN (%) 20137 (78) 9110 80) 20027 (74)
‘Medan duration of response, mo (range) 534184) 470656) 928573)
Patients sil responding at 6 mo, % (range) 43.0 (256.05) 417033.) 55.3 (45760)
PES
PES events, n(%) 9080) so 49 (62)
Median PFS, mo (85% Ch) 352643) 281339) 460865)
mo PFS, % (05% Ci) 4660987565) 291(153428) S09(471-727)
320 233425) 188(68309 435(01-589)
68 (63) 37 (82) 28 (48)
93163118) 504.183) 119 (07-182)
7176787) 458(904813) 8367.05) EII RA
rom
PeerView.com
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Lurbinectedin: Safety’
Grade 1 Grade 3 Grade 4
Hematological abnormalities (regardless of relation to study drug), n (%)*
‘Anemia 9167) 9(9) 0
Leukopenia 53 (50) 20 (19) 10 (10)
‘Neutropenia 27 (26) 22 (21) 26 (25)
Thrombocytopenia 3937) 33) 4(4)
Biochemical abnormalities (regardless of relation to study drug), niN (%)*
Creatinine? 881104 (83) 0 0
Alanine aminotransferase 69/103 (67) 5/103 (5) 0
Aspartate aminotransferase 5203 (50) 1303 (13) 2703 (2)
Y-glutamyftransferase 441103 (43) 21103 (2) 0
Alkaline phosphatase 31/103 (30) 3/103 3) 0
Treatment-related adverse events, n (%
Fatigue 5461) 70) 0
Nausea 34 (32) 0 0
Decreased appetite 2201) o 0
Vomiting 1918) 0 0
Diarthea 13 (14) 1) 0
Febrile neutropenia 0 2(2) 36)
Pneumonia 0 20) 0
Skin vicer 0 14 0
Based on all the patents with laboratory data avaliable. © Version 4.0 of NCHCTCAE grades any creatine Inereases Wom baseline as abnotmalies, even Wereainine
values remain within he normal range —
Y Thgo J etal. Lancet Oncol 202021:545:54 PeerView.com
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Grade 1 Grade 3 Grade 4
Hematological abnormalities (regardless of relation to study drug), n (%)*
‘Anemia 9167) 9(9) 0
Leukopenia 53 (50) 20 (19) 10 (10)
‘Neutropenia 27 (26) 22 (21) 26 (25)
Thrombocytopenia 3937) 33) 4(4)
Biochemical abnormalities (regardless of relation to study drug), niN (%)*
Creatinine? 881104 (83) 0 0
Alanine aminotransferase 69/103 (67) 5/103 (5) 0
Aspartate aminotransferase 5203 (50) 1303 (13) 2703 (2)
Y-glutamyftransferase 441103 (43) 21103 (2) 0
Alkaline phosphatase 31/103 (30) 3/103 3) 0
Treatment-related adverse events, n (%
Fatigue 5461) 70) 0
Nausea 34 (32) 0 0
Decreased appetite 2201) o 0
Vomiting 1918) 0 0
Diarthea 13 (14) 1) 0
Febrile neutropenia 0 2(2) 36)
Pneumonia 0 20) 0
Skin vicer 0 14 0
Based on all the patents with laboratory data avaliable. © Version 4.0 of NCHCTCAE grades any creatine Inereases Wom baseline as abnotmalies, even Wereainine
values remain within he normal range —
Y Thgo J etal. Lancet Oncol 202021:545:54 PeerView.com
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Phase 3 ATLANTIS Trial: Patients With
Relapsed SCLC Receiving Lurbinectedin!
Baseline Characteristics
12)
3 (62)
18.8)
31 (62)
40 (20)
10620)
ET
+ sac
re ‘Stratification factors 2142)
chemotherapy + ECOG PS (0vs21) N
Pe A 070 v 2180 days) cin 1 da
a, ens invevement yes vano) : Core Di
innere
+ ECOG PS 22 + Prior PDAPD-LA (yes ve no) ee rare 30)
+ Measurable or + Investgators preference for contol arm Loren bl Fe
nonmessurable rated 1020)
esse per BL CNS involvement, (4) 36)
RECIST Primary ‘Bost response to AL therapy. n (%)
+ CTFI290 days endpoint: CR sc
os PR 20
so 6012)
Po 10
Unknaum 24)
Screening (up to 28 days) ‘Treatment period Follow-up period TFL N(%)
— A) (— 05
2004
Primary prophylaxis with G-CSF was mandatory in both arms. “eos
1. Navarro A et al ASCO 2022. Abstract 852.
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Relapsed SCLC Receiving Lurbinectedin!
Baseline Characteristics
12)
3 (62)
18.8)
31 (62)
40 (20)
10620)
ET
+ sac
re ‘Stratification factors 2142)
chemotherapy + ECOG PS (0vs21) N
Pe A 070 v 2180 days) cin 1 da
a, ens invevement yes vano) : Core Di
innere
+ ECOG PS 22 + Prior PDAPD-LA (yes ve no) ee rare 30)
+ Measurable or + Investgators preference for contol arm Loren bl Fe
nonmessurable rated 1020)
esse per BL CNS involvement, (4) 36)
RECIST Primary ‘Bost response to AL therapy. n (%)
+ CTFI290 days endpoint: CR sc
os PR 20
so 6012)
Po 10
Unknaum 24)
Screening (up to 28 days) ‘Treatment period Follow-up period TFL N(%)
— A) (— 05
2004
Primary prophylaxis with G-CSF was mandatory in both arms. “eos
1. Navarro A et al ASCO 2022. Abstract 852.
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Phase 3 ATLANTIS Trial: Efficacy of Lurbinectedin +
Doxorubicin and Lurbinectedin Monotherapy'?
+ ATLANTIS did not meet the primary endpoint: median OS was 8.6 mo with lurbinectedin + doxorubicin vs
7.6 mo in the control arm of topotecan or CAV (HR = 0.967, P = .7032)
Single-Agent Lurbinectedin
+ Post-hoc analysis explored the efficacy of single-agent lurbinectedin in patients who completed 10 cycles
of the combination and then switched to lurbinectedin monotherapy per protocol
OS From Randomization
Best Best Response on Lurbinectedin
Response to Monotherapy 3.2 mg/m?
Lurbinectedin EventsiN Median (95% CI)
+ Doxorubicin
30/50 20.7 (15.7-24.8)
CR(n=3) ®
g
A
8
é
SD (n= 19) 4
Anprevina iba 0 3 6 9 1215 18 21 24 27 30 33 36
response EP response Time From Response, mo
1.Paz-Ares Letal. WOLC 2021. Abstract PLO2.03. 2. Navarro À et al. ASCO 2022. Abstract 8524. PeerView.com
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Doxorubicin and Lurbinectedin Monotherapy'?
+ ATLANTIS did not meet the primary endpoint: median OS was 8.6 mo with lurbinectedin + doxorubicin vs
7.6 mo in the control arm of topotecan or CAV (HR = 0.967, P = .7032)
Single-Agent Lurbinectedin
+ Post-hoc analysis explored the efficacy of single-agent lurbinectedin in patients who completed 10 cycles
of the combination and then switched to lurbinectedin monotherapy per protocol
OS From Randomization
Best Best Response on Lurbinectedin
Response to Monotherapy 3.2 mg/m?
Lurbinectedin EventsiN Median (95% CI)
+ Doxorubicin
30/50 20.7 (15.7-24.8)
CR(n=3) ®
g
A
8
é
SD (n= 19) 4
Anprevina iba 0 3 6 9 1215 18 21 24 27 30 33 36
response EP response Time From Response, mo
1.Paz-Ares Letal. WOLC 2021. Abstract PLO2.03. 2. Navarro À et al. ASCO 2022. Abstract 8524. PeerView.com
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Lurbinectedin: Ongoing and Future Trials!
Confirmatory phase 3 trial has been initiated: LAGOON
Eligibility
Relapsed SCLC
One prior platinum-containing regimen
CTFI 230 days
ECOG PS 0-2
‘Adequate hematologic, renal, and
liver function
Stratification
CTFI (290 d, <90 d)
Prior PD-L1/PD-1 (yes or no)
LDH (>ULN or <ULN)
CNS involvement (yes or no)
Investigator's preference of the
control arm.
N=705
Screening up to 28 d
—
1. Besse B et a, ASCO 2029. Abstract TPSa613
PeerView.com/HXN827
Lurbinectedin 2.0 mg/m? IV d 1 + Treatment until progression
irinotecan 75 mg/m? IV a by RECIST v1.1
Primary endpoint: OS
+ Secondary endpoints:
PFS, ORR, DOR, safety,
and PRO
Institutional choice chemotherapy
Topotecan im? oral or 1.5 d
Irinotecan
Treatment period Follow-up period
PeerView.com
Copyright © 2000-2024, PeerView
Confirmatory phase 3 trial has been initiated: LAGOON
Eligibility
Relapsed SCLC
One prior platinum-containing regimen
CTFI 230 days
ECOG PS 0-2
‘Adequate hematologic, renal, and
liver function
Stratification
CTFI (290 d, <90 d)
Prior PD-L1/PD-1 (yes or no)
LDH (>ULN or <ULN)
CNS involvement (yes or no)
Investigator's preference of the
control arm.
N=705
Screening up to 28 d
—
1. Besse B et a, ASCO 2029. Abstract TPSa613
PeerView.com/HXN827
Lurbinectedin 2.0 mg/m? IV d 1 + Treatment until progression
irinotecan 75 mg/m? IV a by RECIST v1.1
Primary endpoint: OS
+ Secondary endpoints:
PFS, ORR, DOR, safety,
and PRO
Institutional choice chemotherapy
Topotecan im? oral or 1.5 d
Irinotecan
Treatment period Follow-up period
PeerView.com
Copyright © 2000-2024, PeerView
CONFERENCE UPDATES & HIGHLIGHTS | #ASCOZ4
Abstract 8094
ae Abstract conclusions: The LUR/IRI combination showed
Title: Efficacy and safety of lurbinectedin (LUR) | oromising antitumor activity and a manageable safety
O Nt EISEN profile in these pts with poor prognosis, particularly those
SCLC: Results fr se 2 expansion cohort 2
MSO ORL 20H) with CTFI>30 d. These encouraging results reinforce the
rationale for including this combination as an experimental
Poster Session; June 3, 2024 arm in the ongoing pivotal phase 3 LAGOON trial
Presenter: Luis G. Paz-Ares (NCT05153239) in relapsed SCLC with CTFI>30 d.
All Patients CTFI<90d CTFI 290 d CTFI>30 d
(n=101) (n=52) (n=49) (n=74)
ORR, % (95% CI) 42.6 (32.8-52.8) 25(14.0-389) 61.2(46.2-74.8) 51.4 (39.4-63.1)
MDOR, mo (95% CI) 84(46127) 82(54117)
MPFS, mo (95% Cl) x x 62 (42-96) 5.6 (4.1-7.2)
MOS, mo (95% CI) 9 78(3589) 14(101161) — 127(9.1-14.1)
OS rate at 12 mo, % (95% Cl) 44.6(33.9-55.3) 28(142-418) 617(466-767) 52.3 (39.8-64.7)
PeerView.com/HXN827
Abstract 8094
ae Abstract conclusions: The LUR/IRI combination showed
Title: Efficacy and safety of lurbinectedin (LUR) | oromising antitumor activity and a manageable safety
O Nt EISEN profile in these pts with poor prognosis, particularly those
SCLC: Results fr se 2 expansion cohort 2
MSO ORL 20H) with CTFI>30 d. These encouraging results reinforce the
rationale for including this combination as an experimental
Poster Session; June 3, 2024 arm in the ongoing pivotal phase 3 LAGOON trial
Presenter: Luis G. Paz-Ares (NCT05153239) in relapsed SCLC with CTFI>30 d.
All Patients CTFI<90d CTFI 290 d CTFI>30 d
(n=101) (n=52) (n=49) (n=74)
ORR, % (95% CI) 42.6 (32.8-52.8) 25(14.0-389) 61.2(46.2-74.8) 51.4 (39.4-63.1)
MDOR, mo (95% CI) 84(46127) 82(54117)
MPFS, mo (95% Cl) x x 62 (42-96) 5.6 (4.1-7.2)
MOS, mo (95% CI) 9 78(3589) 14(101161) — 127(9.1-14.1)
OS rate at 12 mo, % (95% Cl) 44.6(33.9-55.3) 28(142-418) 617(466-767) 52.3 (39.8-64.7)
PeerView.com/HXN827
Overview of DLL3 T-Cell Engager Pipeline’
T-cell
T-cell engager Tarlatamab 1764532 HPN 328
Costing TM
on =p
u
fe
non
1. Modified trom Rudin eta. J Homato! Oncol. 2023:166. PeerView.com
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T-cell
T-cell engager Tarlatamab 1764532 HPN 328
Costing TM
on =p
u
fe
non
1. Modified trom Rudin eta. J Homato! Oncol. 2023:166. PeerView.com
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DeLLphi-301: Tarlatamab (AMG 757) in 23L SCLC12
Key Inclusion Criteria
+ ES-SCLC
Previous treatment with
22 Ines (including
platinum-doublet)
ECOG PS 0,1
Measurable disease
Treated and stable brain
metastases allowed
Part 1: Dose Evaluation
Tariatamab 10 mg
Tarlatamab 100 mg
Part 2: Dose Expansion Part 3: Reduced Inpatient
‘Monitoring Period
+ Primary endpoints: ORR per RECIST v1.1 by BICR, TEAES, tarlatamab
serum concentrations
+ Secondary endpoints: DOR, DCR, PFS per RECIST v1.1 by BICR, OS
1. tps cinicaiis govle@showNCTOS060016. 2. Paz-Aves Leta. ESMO 2023. Abstract LBAS2 PeerView.com
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Copyright © 2000-2024, PeerView
Key Inclusion Criteria
+ ES-SCLC
Previous treatment with
22 Ines (including
platinum-doublet)
ECOG PS 0,1
Measurable disease
Treated and stable brain
metastases allowed
Part 1: Dose Evaluation
Tariatamab 10 mg
Tarlatamab 100 mg
Part 2: Dose Expansion Part 3: Reduced Inpatient
‘Monitoring Period
+ Primary endpoints: ORR per RECIST v1.1 by BICR, TEAES, tarlatamab
serum concentrations
+ Secondary endpoints: DOR, DCR, PFS per RECIST v1.1 by BICR, OS
1. tps cinicaiis govle@showNCTOS060016. 2. Paz-Aves Leta. ESMO 2023. Abstract LBAS2 PeerView.com
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Copyright © 2000-2024, PeerView
DeLLphi-301:
Efficacy of Tarlatamab (AMG 757) in 23L SCLC12
Tarlatamab 10 mg Tarlatamab 100 mg
(n=91)
2892) 21-44)
vo
PR 2120
so zn
po 13 (18)
NEMO postbaseine scan EI
Osmanen GOR 3 me a ae
DCR. ns) (5% CH 70 70) (60-79) 55 63) 62-73)
Median PFS, mo (85% CI) 490967) 392844)
Median OS, mo (95% Cl) 143 (08NE) NE (124NE)
Onset and Duration of Response
A Fist response (paral response or better) I Disease progression > Ongoing treatment. Death
Tarlatamab 10 mg (n = 40) Tarlatamab 100 mg (n = 28)
=
o © 20 % 4 % & 7 % 0 10
Duration of Treatment, wk .
1.Paz-Ares Let al ESMO 2023. Abstract LBAS2. 2. Ah Met al. N Engl Med 2025:389 2063-2075. PeerView.com
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Efficacy of Tarlatamab (AMG 757) in 23L SCLC12
Tarlatamab 10 mg Tarlatamab 100 mg
(n=91)
2892) 21-44)
vo
PR 2120
so zn
po 13 (18)
NEMO postbaseine scan EI
Osmanen GOR 3 me a ae
DCR. ns) (5% CH 70 70) (60-79) 55 63) 62-73)
Median PFS, mo (85% CI) 490967) 392844)
Median OS, mo (95% Cl) 143 (08NE) NE (124NE)
Onset and Duration of Response
A Fist response (paral response or better) I Disease progression > Ongoing treatment. Death
Tarlatamab 10 mg (n = 40) Tarlatamab 100 mg (n = 28)
=
o © 20 % 4 % & 7 % 0 10
Duration of Treatment, wk .
1.Paz-Ares Let al ESMO 2023. Abstract LBAS2. 2. Ah Met al. N Engl Med 2025:389 2063-2075. PeerView.com
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DeLLphi-301:
Efficacy of Tarlatamab (AMG 757) in SCLC12
Tarlatamab Tarlatamab
100 mg
(n= 88)
3(108-NE) NE(2
PFS, Proportion
= a " :
te .. @ 8 o» 2
PeerView.com
1.Paz-Ares Letal. ESMO 2023. Abstract LBAG2. 2. Ahn M e al. N Engl J Med. 2023:389:2063-2075,
PeerView.com/HXN827 Copyright © 2000-2024, PeerView
Efficacy of Tarlatamab (AMG 757) in SCLC12
Tarlatamab Tarlatamab
100 mg
(n= 88)
3(108-NE) NE(2
PFS, Proportion
= a " :
te .. @ 8 o» 2
PeerView.com
1.Paz-Ares Letal. ESMO 2023. Abstract LBAG2. 2. Ahn M e al. N Engl J Med. 2023:389:2063-2075,
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DeLLphi-301 Study: Safety Summary’
+ Tarlatamab demonstrated a favorable safety profile, with a low rate of discontinuations due to TRAEs
+ Most common TRAE was CRS, which primarily occurred in cycle 1 and was mostly grade 1-2 and generally
manageable with supportive care
+ Discontinuation of tarlatamab due to TRAEs was low (3%)
Part1+2 Parti Part3 Part1+2 Parti Part3
Tarlatamab Tarlatamab Tarlatamab | Most Common TEAES in Tarlatamab Tarlatamab Tarlatamab
10mg 100mg 10mg |220%ofPatients, n (%) 10mg 100mg 10mg
TEAEs, n (%)
(n=99) (n=87) (n=34) (n=99) (n=87) (n=34)
Any grade We) — 87(100) 34(100) |CRS 49 (49) EI] 19 (56)
Grade 23 57 (58) 56 (64) 2069) | Grade 12 49 (49) 48 (55) 18(53)
Related to tarlatamab, any grade 89 (90) 81 (63) 29(85) | Grade 23 o 516) 10)
Grade 23 29129) 2933) 5(15) Decreased appetite 25 (25) 38 (44) 13 68)
Fatal o o 108) Pyrexia 38 (38) 2933) 204)
Leading to dose interuptionireduction 14 (14) 25 29) 36) _] Constipation 28 (28) 22(25) 84
Leading to discontinuation 40 29) o Anemia 26 (28) 22 (25) 9/25)
Asthenia 20 (20) 2124) 10(29)
Dysgeusia 24 (24) 12(14) 14(41)
Fatigue 2121) 17.20) 326)
‘Ongoing phase 3 DeLLphi-304 study will compare efficacy
and safety of tarlatamab (10 mg Q2W) with standard-of-care chemotherapy
1.Paz-Ares Let al ESMO 2023. Abstract LBAS2. 2. Ahn M et al. N Eng! Med. 2028;388 2068-2075, PeerView.com
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+ Tarlatamab demonstrated a favorable safety profile, with a low rate of discontinuations due to TRAEs
+ Most common TRAE was CRS, which primarily occurred in cycle 1 and was mostly grade 1-2 and generally
manageable with supportive care
+ Discontinuation of tarlatamab due to TRAEs was low (3%)
Part1+2 Parti Part3 Part1+2 Parti Part3
Tarlatamab Tarlatamab Tarlatamab | Most Common TEAES in Tarlatamab Tarlatamab Tarlatamab
10mg 100mg 10mg |220%ofPatients, n (%) 10mg 100mg 10mg
TEAEs, n (%)
(n=99) (n=87) (n=34) (n=99) (n=87) (n=34)
Any grade We) — 87(100) 34(100) |CRS 49 (49) EI] 19 (56)
Grade 23 57 (58) 56 (64) 2069) | Grade 12 49 (49) 48 (55) 18(53)
Related to tarlatamab, any grade 89 (90) 81 (63) 29(85) | Grade 23 o 516) 10)
Grade 23 29129) 2933) 5(15) Decreased appetite 25 (25) 38 (44) 13 68)
Fatal o o 108) Pyrexia 38 (38) 2933) 204)
Leading to dose interuptionireduction 14 (14) 25 29) 36) _] Constipation 28 (28) 22(25) 84
Leading to discontinuation 40 29) o Anemia 26 (28) 22 (25) 9/25)
Asthenia 20 (20) 2124) 10(29)
Dysgeusia 24 (24) 12(14) 14(41)
Fatigue 2121) 17.20) 326)
‘Ongoing phase 3 DeLLphi-304 study will compare efficacy
and safety of tarlatamab (10 mg Q2W) with standard-of-care chemotherapy
1.Paz-Ares Let al ESMO 2023. Abstract LBAS2. 2. Ahn M et al. N Eng! Med. 2028;388 2068-2075, PeerView.com
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FDA Approval of Tarlatamab!
On May 16, 2024, the FDA granted accelerated
approval to tarlatamab for ES-SCLC with disease
progression on or after platinum-based chemotherapy
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On May 16, 2024, the FDA granted accelerated
approval to tarlatamab for ES-SCLC with disease
progression on or after platinum-based chemotherapy
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INFERENCE UPDATES & HIGHLIGHTS | #ASCO24
Abstract conclusions: Tarlatamab showed
promising efficacy and a favorable benefit-risk
profile in patients with previously treated SCLC
and stable brain metastases.
PeerView.com/HXN827
oR
(5% ci)
Responders
wh sustained
response at 12 mo,
KM estimate, %
(5% ch)
PES, median, mo
sx ch)
(08, median, mo
(sic)
TE
Yes
(m=22)
ss
23.
758)
74
one,
143
Ne)
No
@=7™
384
es.
41)
4
aus)
ne
an)
41
ess)
NE
(MENE)
2024 ASCO
ANA MEET)
Overall (n= 188)
29 ss 39
(543 6682 (2744)
NE NE NE
(GONE) (143NE) (ONE)
Copyright © 2000-2024, PeerView
Abstract conclusions: Tarlatamab showed
promising efficacy and a favorable benefit-risk
profile in patients with previously treated SCLC
and stable brain metastases.
PeerView.com/HXN827
oR
(5% ci)
Responders
wh sustained
response at 12 mo,
KM estimate, %
(5% ch)
PES, median, mo
sx ch)
(08, median, mo
(sic)
TE
Yes
(m=22)
ss
23.
758)
74
one,
143
Ne)
No
@=7™
384
es.
41)
4
aus)
ne
an)
41
ess)
NE
(MENE)
2024 ASCO
ANA MEET)
Overall (n= 188)
29 ss 39
(543 6682 (2744)
NE NE NE
(GONE) (143NE) (ONE)
Copyright © 2000-2024, PeerView
First-in-Human Dose Escalation Trial of BI-764532
in Patients With SCLC or NEC!
Key Inclusion Criteria
‘Advanced SCLC,
LONEC, or epNEC
DLL3 positive (archived tissue
‘or in-study biopsy) according
Regimen B
Regimen B1 Regimen B2
BLRM
to central review
Failed/neligible for available
standard therapies (21 line
of platinum-based chemotherapy
‘Adequate liver, bone marrow,
and renal function
Switch to B1 based ‘Switch to step-in dosing (82)
on regimen A data based on regimen A and B1 data
ECOG PS 0/1 + MD + Objective response (RECIST v1.1)
+ DLTs in the MTD evaluation period + PK parameters.
Patients are treated until disease worsening or a maximum duration of 36 months
1. Wermke Met al, ASCO 2023. Abstract 8502.
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in Patients With SCLC or NEC!
Key Inclusion Criteria
‘Advanced SCLC,
LONEC, or epNEC
DLL3 positive (archived tissue
‘or in-study biopsy) according
Regimen B
Regimen B1 Regimen B2
BLRM
to central review
Failed/neligible for available
standard therapies (21 line
of platinum-based chemotherapy
‘Adequate liver, bone marrow,
and renal function
Switch to B1 based ‘Switch to step-in dosing (82)
on regimen A data based on regimen A and B1 data
ECOG PS 0/1 + MD + Objective response (RECIST v1.1)
+ DLTs in the MTD evaluation period + PK parameters.
Patients are treated until disease worsening or a maximum duration of 36 months
1. Wermke Met al, ASCO 2023. Abstract 8502.
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First-in-Human Dose Escalation Trial of BI-764532 in
Best Change From Baseline
in SOD, %
Efficacy by Tumor Type (Doses 290 g/kg)
Patients With SCLC or NEC!
n(%)
so
PD
DCR
NE
SCLC epNEC LCNEC
; (n=27; (n=5;
100
1006) 5(19) 3(60)
10(26) 7(26) 240)
1261) 1348 0
20(51) 12(4) 5(100)
7(18) 2m 0
Efficacy, ie, tumor shrinkage
was observed across all
enrolled tumor types.
* Etescy population: 21 postbaseline tumor assessment or permanently discontinued prior o tumor assessment: responses evaluated per RECIST vi. entera.
* Discontinued prior to tumor assessment
1. Werke Metal. ASCO 2023, Abstract 8802.
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Best Change From Baseline
in SOD, %
Efficacy by Tumor Type (Doses 290 g/kg)
Patients With SCLC or NEC!
n(%)
so
PD
DCR
NE
SCLC epNEC LCNEC
; (n=27; (n=5;
100
1006) 5(19) 3(60)
10(26) 7(26) 240)
1261) 1348 0
20(51) 12(4) 5(100)
7(18) 2m 0
Efficacy, ie, tumor shrinkage
was observed across all
enrolled tumor types.
* Etescy population: 21 postbaseline tumor assessment or permanently discontinued prior o tumor assessment: responses evaluated per RECIST vi. entera.
* Discontinued prior to tumor assessment
1. Werke Metal. ASCO 2023, Abstract 8802.
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Phase 1/2 Study of HPN328 in Patients With SCLC
and Other NECs!
Dose Es.
‘Ongoing 1 mg priming step-dose
escalation and optimization cohorts
Early fixed dose and step-dose
escalation cohorts
Target population
‘Small cel ung cancer (SCLC)
relapsedirefractory after platinum
chemotherapy
+ Neuroendocrine prostate cancer
(NEPC) relapsed refractor to Standard
of Care (SOC)
+ Other high-grade neuroendocrine
neoplasms (NEN) relapsedirefractory
to SOC or no SOC available; DLL3
expression by IHC required
+ One-mg o 24mg cohorts use a 12mg intermediate sep up pir to moving to 24mg target." Sil enon; protocol low for hart of up o 17 patents, depending on
cohort“ Alezo combination cohorts recent opened; data tobe presented tater date .
ay Net a ESO 2023 Aste abe PeerView.com
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and Other NECs!
Dose Es.
‘Ongoing 1 mg priming step-dose
escalation and optimization cohorts
Early fixed dose and step-dose
escalation cohorts
Target population
‘Small cel ung cancer (SCLC)
relapsedirefractory after platinum
chemotherapy
+ Neuroendocrine prostate cancer
(NEPC) relapsed refractor to Standard
of Care (SOC)
+ Other high-grade neuroendocrine
neoplasms (NEN) relapsedirefractory
to SOC or no SOC available; DLL3
expression by IHC required
+ One-mg o 24mg cohorts use a 12mg intermediate sep up pir to moving to 24mg target." Sil enon; protocol low for hart of up o 17 patents, depending on
cohort“ Alezo combination cohorts recent opened; data tobe presented tater date .
ay Net a ESO 2023 Aste abe PeerView.com
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Phase 1/2 Study of HPN328 in Patients With SCLC
and Other NECs!
Response in Patients Treated at 2 Minimal Effective Dose (21.215 mg)
100 With 21 Postbaseline Assessment (n = 49)
+ Axis capped
at 100%,
although largest
were
>100.0%; EC-PR
= extracranial
partial response
per mRECIST
8
i
fl
E
5
bl
bl
* NEN patent enroled wih 0% DLL3 expression rior o protocol requiement In patents with opportnty to have two scans or scontinued pro o confematory
scan dueto AE or PD. * Patients on study wih ony one imaging assessment o date. Incudes RECIST:based normalzaton ol lymph node size; patent achieved
‘PR porto CR, so considered a confrmed response. “Paten! with brain meta at week 2 kradiled wth contnued extacranial response for 64 weeks. a
1. ChouchuryN et al ESMO 2023, Abstract C88 PeerView.com
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and Other NECs!
Response in Patients Treated at 2 Minimal Effective Dose (21.215 mg)
100 With 21 Postbaseline Assessment (n = 49)
+ Axis capped
at 100%,
although largest
were
>100.0%; EC-PR
= extracranial
partial response
per mRECIST
8
i
fl
E
5
bl
bl
* NEN patent enroled wih 0% DLL3 expression rior o protocol requiement In patents with opportnty to have two scans or scontinued pro o confematory
scan dueto AE or PD. * Patients on study wih ony one imaging assessment o date. Incudes RECIST:based normalzaton ol lymph node size; patent achieved
‘PR porto CR, so considered a confrmed response. “Paten! with brain meta at week 2 kradiled wth contnued extacranial response for 64 weeks. a
1. ChouchuryN et al ESMO 2023, Abstract C88 PeerView.com
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Tarlatamab and Other DLL3 T-Cell Engagers: Ongoing Trials
Agent Disease Setting NCT Notes
Tarlatamab LS-SCLC; 1L maintained NCTO6117774 Tarlatamab vs placebo following chemo RT
Tarlatamab ES-SCLC; 1L maintained NCTO6211036 Tarlatamab + durvalumab vs durvalumab following EP + PD-L1
RO7616789 R/RSCLCandNECs NCTO5619744 Trispecific, including CD137 Ab
QLS31904 R/R SCLC and NECs NCTO5461287 -
BI764532 ES-SCLC; 1L maintained NCT06077500 Combo with EP + PD-L1
BI 764532 RIR SCLC NCT05990738 Combo with topotecan
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Agent Disease Setting NCT Notes
Tarlatamab LS-SCLC; 1L maintained NCTO6117774 Tarlatamab vs placebo following chemo RT
Tarlatamab ES-SCLC; 1L maintained NCTO6211036 Tarlatamab + durvalumab vs durvalumab following EP + PD-L1
RO7616789 R/RSCLCandNECs NCTO5619744 Trispecific, including CD137 Ab
QLS31904 R/R SCLC and NECs NCTO5461287 -
BI764532 ES-SCLC; 1L maintained NCT06077500 Combo with EP + PD-L1
BI 764532 RIR SCLC NCT05990738 Combo with topotecan
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DLL3 CARs: Phase 1 Trial of AMG119 (DLL3 CAR-T)
in Relapsed SCLC’
AMG 119 sé Fly human
Adoptive chimeric antigen ng anti-DLL3 scFv
receptor (CAR) T cell therapy
(NCT03319940) Tee)
Costimulatory
‘oman
(eats otvaten Prose)
AO 119 an y
FOR
£ sé |?
Corsa) 38 3
ss
| a
Oyen vain TO mou. PeerView.com
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in Relapsed SCLC’
AMG 119 sé Fly human
Adoptive chimeric antigen ng anti-DLL3 scFv
receptor (CAR) T cell therapy
(NCT03319940) Tee)
Costimulatory
‘oman
(eats otvaten Prose)
AO 119 an y
FOR
£ sé |?
Corsa) 38 3
ss
| a
Oyen vain TO mou. PeerView.com
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DLL3 CARs: Phase 1 Trial of AMG119 (DLL3 CAR-T)
in Relapsed SCLC’
Waterfall Plot Showing Best m ROLLS y HOLL sous
Tessin Tessi2+ Tessie
Change in Sum of Lesion
Diameters From Baseline pA En
Best Overall Response
3
8
& ff fF &F& FEA
Timepoint
Best SLD Change
From Baseline, %
¿58853038
Best responses observed in those
ith highest DLL3
by IHC
008 00s 00,
Patient ID
Patent 008 response was considered nevaluable as cou not be determined ifthe patents response changed rom sable disease o progressive disease within
a protocol ime n
1 Bera Letal SITO 2022 Abstract 807. PeerView.com
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in Relapsed SCLC’
Waterfall Plot Showing Best m ROLLS y HOLL sous
Tessin Tessi2+ Tessie
Change in Sum of Lesion
Diameters From Baseline pA En
Best Overall Response
3
8
& ff fF &F& FEA
Timepoint
Best SLD Change
From Baseline, %
¿58853038
Best responses observed in those
ith highest DLL3
by IHC
008 00s 00,
Patient ID
Patent 008 response was considered nevaluable as cou not be determined ifthe patents response changed rom sable disease o progressive disease within
a protocol ime n
1 Bera Letal SITO 2022 Abstract 807. PeerView.com
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Coming Back to Our Case
An 80-year-old woman newly diagnosed with ES-SCLC received initial treatment with EP + durvalumab
‘She completed 4 cycles of induction chemoimmunotherapy with delays in initiating C3 and C4
because of delayed count recovery
She transitioned to durvalumab maintenance
Routine restaging CT scans after 7 cycles of Q4W maintenance durvalumab unfortunately
demonstrated multiple new or progressive hepatic lesions
MRI of brain shows 4 sub-centimeter parenchymal lesions consistent with metastases and
without perilesional edema
ECOG PS remains preserved, and she wants to explore other therapeutic options
PeerView.com/HXN827 Copyright © 2000-2024, Peerview
An 80-year-old woman newly diagnosed with ES-SCLC received initial treatment with EP + durvalumab
‘She completed 4 cycles of induction chemoimmunotherapy with delays in initiating C3 and C4
because of delayed count recovery
She transitioned to durvalumab maintenance
Routine restaging CT scans after 7 cycles of Q4W maintenance durvalumab unfortunately
demonstrated multiple new or progressive hepatic lesions
MRI of brain shows 4 sub-centimeter parenchymal lesions consistent with metastases and
without perilesional edema
ECOG PS remains preserved, and she wants to explore other therapeutic options
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Expert Panel Discussion
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Research and Clinical Accelerator
Assessing the Potential of Emerging
Therapies for SCLC: Focus on the ADCs
Mark M. Awad, MD, PhD
Director of Clinical Research
Program Director, Advanced Fellowship in Thoracic Oncology
Physician
Associate Professor of Medicine
Harvard Medical School
Associate Chief of the Lowe Center for Thoracic Oncology
Dana-Farber Cancer Institute
Boston, Massachusetts
=
LY A
Copyright O 2000-2024, Peerview
Assessing the Potential of Emerging
Therapies for SCLC: Focus on the ADCs
Mark M. Awad, MD, PhD
Director of Clinical Research
Program Director, Advanced Fellowship in Thoracic Oncology
Physician
Associate Professor of Medicine
Harvard Medical School
Associate Chief of the Lowe Center for Thoracic Oncology
Dana-Farber Cancer Institute
Boston, Massachusetts
=
LY A
Copyright O 2000-2024, Peerview
ADCs: Understanding Their Composition and Structure’
Antigen ta
High homogeneous expression in tumor
Limited/absent expression in normal tissue
Limited heterogeneity
Efficient intemalization following ADC
binding
Drug/payload
+ Highly potent (eg, microtubule inhibitor,
DNA-damaging agents)
Amenable to linker attachment
+ Maximized drug-to-antibody ratio
1. Marks S, Naidoo J. Lung Cancer, 2022:103:5948.
PeerView.com/HXN827
‘Antibody
High affinity and avidity for target antigen
Long half-life
Conjugation sites with minimal impact on.
ADC stability, internalization, and PK (eg,
cysteine, lysine)
Chimeric or humanized (decreasing
immunogenicity)
Linker
+ Controlled release of payload
= Noncleavable (eg, lysosomal
degradation of mAb)
= Cleavable (eg, acid/redox/iysosomal
sensitive)
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Antigen ta
High homogeneous expression in tumor
Limited/absent expression in normal tissue
Limited heterogeneity
Efficient intemalization following ADC
binding
Drug/payload
+ Highly potent (eg, microtubule inhibitor,
DNA-damaging agents)
Amenable to linker attachment
+ Maximized drug-to-antibody ratio
1. Marks S, Naidoo J. Lung Cancer, 2022:103:5948.
PeerView.com/HXN827
‘Antibody
High affinity and avidity for target antigen
Long half-life
Conjugation sites with minimal impact on.
ADC stability, internalization, and PK (eg,
cysteine, lysine)
Chimeric or humanized (decreasing
immunogenicity)
Linker
+ Controlled release of payload
= Noncleavable (eg, lysosomal
degradation of mAb)
= Cleavable (eg, acid/redox/iysosomal
sensitive)
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ADC Mechanisms of Action!
Antibody engagement leads to
yload-independent antitumor activity
via several mechanisms: The payload is released from endosomes
and/or lysosomes, and takes its effect on
Cells, leading to cell death
Most ADCs are internalized in tumor cells nbrane-permeable payloads enter
1. Fe-mediated stimulation of immune cell
2. Disruption of receptor dimerization
+ « Fomedated
stimulation
ol mmune
estetecio Jl
IININING
NRA
Fe region of the mAb component of ADCs can orchestrate ADCC
1. Drago JZ eta. Nat Rev Cin Oncol 2021:18:327:344 PeerView.com
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Antibody engagement leads to
yload-independent antitumor activity
via several mechanisms: The payload is released from endosomes
and/or lysosomes, and takes its effect on
Cells, leading to cell death
Most ADCs are internalized in tumor cells nbrane-permeable payloads enter
1. Fe-mediated stimulation of immune cell
2. Disruption of receptor dimerization
+ « Fomedated
stimulation
ol mmune
estetecio Jl
IININING
NRA
Fe region of the mAb component of ADCs can orchestrate ADCC
1. Drago JZ eta. Nat Rev Cin Oncol 2021:18:327:344 PeerView.com
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Drug-to-Antibody Ratio (DAR)!
+ Average number of payload a TVA
moieties attached to each mAb Bs
Px,
+ Range from 2-8
Microtubule —
+ Crucial in determining ADC disruption
potency and toxicity
+ Higher DARs may increase
cell death
activity, but also may broaden ra
off-target effects
re
+ Higher DARs might also enhance
drug clearance by the liver
damage
1.LUB etal WLC 2022. Oral presentation, PeerView.com
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+ Average number of payload a TVA
moieties attached to each mAb Bs
Px,
+ Range from 2-8
Microtubule —
+ Crucial in determining ADC disruption
potency and toxicity
+ Higher DARs may increase
cell death
activity, but also may broaden ra
off-target effects
re
+ Higher DARs might also enhance
drug clearance by the liver
damage
1.LUB etal WLC 2022. Oral presentation, PeerView.com
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Ifinatamab Deruxtecan (I-DXd; DS-7300)!
+ 1-DXd is a B7-H3-directed ADC composed of 3 parts
Payload mechanism
— A fully human anti-B7-H3 IgG1 mAb of action: topoisomerase |
— A topoisomerase | inhibitor payload (an exatecan derivative, DXd) (MÈRE
High potency of payload
Optimized DAR ~4
Payload with short systemic
— A tetrapeptide-based cleavable linker that covalently bonds
the other 2 components
Humanized Anti-87-43 half-life
sort erin + Stable linker payload
x + Tumor-selective cleavable
= linker
Clenvabe Tetrapeptide-Based Linker
‘Topoisomerase | Inhibitor + Bystander antitumor effect
Payload (OX¢)
1. Patel Metal. ESMO 2023, Abstract 690P. PeerView.com
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+ 1-DXd is a B7-H3-directed ADC composed of 3 parts
Payload mechanism
— A fully human anti-B7-H3 IgG1 mAb of action: topoisomerase |
— A topoisomerase | inhibitor payload (an exatecan derivative, DXd) (MÈRE
High potency of payload
Optimized DAR ~4
Payload with short systemic
— A tetrapeptide-based cleavable linker that covalently bonds
the other 2 components
Humanized Anti-87-43 half-life
sort erin + Stable linker payload
x + Tumor-selective cleavable
= linker
Clenvabe Tetrapeptide-Based Linker
‘Topoisomerase | Inhibitor + Bystander antitumor effect
Payload (OX¢)
1. Patel Metal. ESMO 2023, Abstract 690P. PeerView.com
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DS7300-A-J101 (NCT04145622): Study Design!
Patients with
Sans aba Part 1: Dose-Escalation Part 2: Dose-Expansion (12.0 mg/kg)
or metastatic solid tumors 9
(unselected for B7-H3 I-DXd IV Q3W monotherapy I-DXd IV Q3W monotherapy for
expression) for advanced solid tumors? selected advanced solid tumors
N= 205
16.0 mg/kg
Key primary endpoints oman) Cohort 1 En
+ Dose escalation: DLTs, SAEs, TEAEs AES! 80 mgkg (planned n = 40)
+ Dose expansion: ORR, DOR, DCR, PFS, OS 64 mgkg CORCLSTCRE!
Key secondary endpoints AS O (planned n = 40)
+ PK 32mgkg
. 16mong Cohort 3: sqNSCLC
+ Immunogenicit
pen 08 maka (planned n = 40)
Tumor pes included advanceclunresecable or metastatic HNSCC, ESCC, mCRPC, saNSCLO, SCLC, badder cancer, sarcoma, endometal cancer, melanoma,
and breast cancer .
{Patel Metal, ESMO 2023, Abstract 690P. PeerView.com
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Patients with
Sans aba Part 1: Dose-Escalation Part 2: Dose-Expansion (12.0 mg/kg)
or metastatic solid tumors 9
(unselected for B7-H3 I-DXd IV Q3W monotherapy I-DXd IV Q3W monotherapy for
expression) for advanced solid tumors? selected advanced solid tumors
N= 205
16.0 mg/kg
Key primary endpoints oman) Cohort 1 En
+ Dose escalation: DLTs, SAEs, TEAEs AES! 80 mgkg (planned n = 40)
+ Dose expansion: ORR, DOR, DCR, PFS, OS 64 mgkg CORCLSTCRE!
Key secondary endpoints AS O (planned n = 40)
+ PK 32mgkg
. 16mong Cohort 3: sqNSCLC
+ Immunogenicit
pen 08 maka (planned n = 40)
Tumor pes included advanceclunresecable or metastatic HNSCC, ESCC, mCRPC, saNSCLO, SCLC, badder cancer, sarcoma, endometal cancer, melanoma,
and breast cancer .
{Patel Metal, ESMO 2023, Abstract 690P. PeerView.com
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DS7300-A-J101 (NCT04145622): I-DXd Efficacy in SCLC
(24.8 mg/kg Cohort)13
Efficacy Population (24.8 mg/kg) n=21
SCLC Confirmed ORR, n (%, 95% Cl) 11 (62.4, 298-743)
1 Starting dose level Confirmed CR, n (%) 148)
80] I 64 mgikg D 8.0 mg/kg Ml 12.0 mg/kg Il 16.0 mg/kg Confirmed PR, n (%) 10.476)
Median TTR, mo (95% Cl) 12(1.244)
‘Median DOR, mo (95% Cl) 59(28-7.5)
Median PFS, mo (95% CI) 56 (3.9-8.1)
Median OS, mo (95% Cl) 122(64-NE)
Median follow-up, mo (95% CI) 11.7 (46-129)
Safety Population (All Doses) 2
Number of prior systemic regimens, median (range) 2(1-7)
Best Change From Baseline, %
Platinum-based chemotherapy, n (%) 22(100)
Immunotherapy, n (%) 18 (81.8)
Irinotecan or topotecan, n (%) 522.77
Topotecan, n (%) 3(13.6)
Change rom baseline in target lesions was assessed per RECIST v1.1, AN21 patients were evaluable at baselne, bul one id not have any posbaseln tumor assessments, and so was nat
included in the waterfall pl. "One patient received bath. à
{Patel M et al ESMO 2023, Abstract 690P° PeerView.com
PeerView.com/HXN827 Copyright © 2000-2024, Peerview
(24.8 mg/kg Cohort)13
Efficacy Population (24.8 mg/kg) n=21
SCLC Confirmed ORR, n (%, 95% Cl) 11 (62.4, 298-743)
1 Starting dose level Confirmed CR, n (%) 148)
80] I 64 mgikg D 8.0 mg/kg Ml 12.0 mg/kg Il 16.0 mg/kg Confirmed PR, n (%) 10.476)
Median TTR, mo (95% Cl) 12(1.244)
‘Median DOR, mo (95% Cl) 59(28-7.5)
Median PFS, mo (95% CI) 56 (3.9-8.1)
Median OS, mo (95% Cl) 122(64-NE)
Median follow-up, mo (95% CI) 11.7 (46-129)
Safety Population (All Doses) 2
Number of prior systemic regimens, median (range) 2(1-7)
Best Change From Baseline, %
Platinum-based chemotherapy, n (%) 22(100)
Immunotherapy, n (%) 18 (81.8)
Irinotecan or topotecan, n (%) 522.77
Topotecan, n (%) 3(13.6)
Change rom baseline in target lesions was assessed per RECIST v1.1, AN21 patients were evaluable at baselne, bul one id not have any posbaseln tumor assessments, and so was nat
included in the waterfall pl. "One patient received bath. à
{Patel M et al ESMO 2023, Abstract 690P° PeerView.com
PeerView.com/HXN827 Copyright © 2000-2024, Peerview
DS7300-A-J101 (NCT04145622): B7-H3 Correlative Analysis!
+ No trend of correlation between B7-H3 expression and efficacy was observed in the SCLC subset
38 8
B7-H3 Expression Level
mem/cyto H-Score
3
o
H-score
(median)
H-score
(range)
SCLC—B7-H3 Level by BOR Status for Evaluable Patients (n = 17)
ur
Cl
n=1
170
170-170
PR
n=9
105
70-150
SD
n=4
158
66-190
PD
n=2
89
10-168
E
n=1
90
90-90
B7-H3 mem/eyto H-score 115
at baseline, median (range) (10-190)
H-score at baseline, range 10-105
Unconfirmed ORR, n (%) 5 (62.5)
Median PFS, mo 58
(95% Cl) (0.7-NE)
Median OS, mo 122
(95% Cl) (5.8-NE)
At baseline. Low B7-H3 was defined as an H-core lower han the median H-2core in the SCLC B7-H-evalable population. High 87-H3 was defined as an H-score
Higher than the median H-score in the SCLC B7-H3-evaluabe population
41 Patel M etal ESMO 2023, Abstract 690P.
PeerView.com/HXN827
High B7-H3"
(n=9)
115-190
5 (65.6)
53
(1.4-NE)
69
(28-NE)
PeerView.com
Copyright © 2000-2024, PeerView
+ No trend of correlation between B7-H3 expression and efficacy was observed in the SCLC subset
38 8
B7-H3 Expression Level
mem/cyto H-Score
3
o
H-score
(median)
H-score
(range)
SCLC—B7-H3 Level by BOR Status for Evaluable Patients (n = 17)
ur
Cl
n=1
170
170-170
PR
n=9
105
70-150
SD
n=4
158
66-190
PD
n=2
89
10-168
E
n=1
90
90-90
B7-H3 mem/eyto H-score 115
at baseline, median (range) (10-190)
H-score at baseline, range 10-105
Unconfirmed ORR, n (%) 5 (62.5)
Median PFS, mo 58
(95% Cl) (0.7-NE)
Median OS, mo 122
(95% Cl) (5.8-NE)
At baseline. Low B7-H3 was defined as an H-core lower han the median H-2core in the SCLC B7-H-evalable population. High 87-H3 was defined as an H-score
Higher than the median H-score in the SCLC B7-H3-evaluabe population
41 Patel M etal ESMO 2023, Abstract 690P.
PeerView.com/HXN827
High B7-H3"
(n=9)
115-190
5 (65.6)
53
(1.4-NE)
69
(28-NE)
PeerView.com
Copyright © 2000-2024, PeerView
DS7300-A-J101 (NCT04145622): Overall Safety Summary!
scLe ESCC mERPC sqNSCLC Total
(n=22) (n=29) (n=75) (n=18) 17
ES = 1
Median treatment duration (range), wk an on 4) ps (0. in 4 73)
22 29 75 17 172
Any TEAEs,? n (%) (100) (100) (100) (94.4) (98.9)
8 13 35 12 76
TEAE of CTCAE grade 23, n (%) (36.4) (44.8) (46.7) (66.7) (43.7)
TEAE associated with drug discontinuation, n (%) @ 7) es do ven Go)
TEAE associated with dose interruption, n (%) Kom Pa) con Es Ga
TEAE associated with dose reduction, n (%) a 6) de 8) 035) es (103)
Treatment-related TEAE associated with death, n (%) 0 o o 0 ocr
includes patients with SCLC, ESCC, mCRPC, sqNSCLC and other tumor types. * Adverse evens were coded using MegDRA, version 251
One patent wth endometil cancer who received FOXG at 16.0 mghkg experienced grade 5 ILD, —
1. Patel Met al ESMO 2029. Abstract 6907. PeerView.com
PeerView.com/HXN827 Copyright © 2000-2024, PeerView
scLe ESCC mERPC sqNSCLC Total
(n=22) (n=29) (n=75) (n=18) 17
ES = 1
Median treatment duration (range), wk an on 4) ps (0. in 4 73)
22 29 75 17 172
Any TEAEs,? n (%) (100) (100) (100) (94.4) (98.9)
8 13 35 12 76
TEAE of CTCAE grade 23, n (%) (36.4) (44.8) (46.7) (66.7) (43.7)
TEAE associated with drug discontinuation, n (%) @ 7) es do ven Go)
TEAE associated with dose interruption, n (%) Kom Pa) con Es Ga
TEAE associated with dose reduction, n (%) a 6) de 8) 035) es (103)
Treatment-related TEAE associated with death, n (%) 0 o o 0 ocr
includes patients with SCLC, ESCC, mCRPC, sqNSCLC and other tumor types. * Adverse evens were coded using MegDRA, version 251
One patent wth endometil cancer who received FOXG at 16.0 mghkg experienced grade 5 ILD, —
1. Patel Met al ESMO 2029. Abstract 6907. PeerView.com
PeerView.com/HXN827 Copyright © 2000-2024, PeerView
IDeate-Lung02 (NCT06203210): Phase 3 Trial in Relapsed
SCLC After 1 Prior Line of Platinum-Based Therapy!
Abstract TPS8126 A global, multicenter, randomized, open-label, phase 3 trial
in patients with relapsed SCLC who have received one prior line
of platinum-based therapy and have an ECOG PS of st
Poster Session; June 3, 2024
Presenter: Taofeek K. Owonikoko
Key inclusion Criteria Dual primary efficacy endpoints:
Relapsed SCLC ‘ORR per RECIST v1.1 by BICR
Received 1 prior line of platinum-based and OS
therapy 2
ECOG PS 0, 1 ‘Secondary efficacy endpoints:
Patients with asymptomatic brain metastases 4 ‘ORR per investigator; PFS; DoR,
are eligible DCR and time to response by BICR
and investigator, and PROS
statieation: TPC (topotecan,
CTF after AL therapy (<90 vs 290 days) amrubicin, of Safety endpoints:
TPC (topotecan vs amrubicin vs lurbinectedin TEAES, deaths, serious TEAES,
lurbinectedin) and TEAES leading to dose
Prior treatment with PD-(L)1 (yes vs no) 234 ‘modification or discontinuation
a ono ren Study treatment continues unt disease progression
etoringes (res veo) unacoeptable toxicity, withdrawal of consent, death,
loss to follow-up, or other reasons per protocol
+ A phase 2 study (NCT05280470) of patients with 2L or 3L ES-SCLC is also currently ongoing
1.Owonikoko T et al. ASCO 2024. Abstract TPSB126, PeerView.com
PeerView.com/HXN827 Copyright © 2000-2024, Peerview
SCLC After 1 Prior Line of Platinum-Based Therapy!
Abstract TPS8126 A global, multicenter, randomized, open-label, phase 3 trial
in patients with relapsed SCLC who have received one prior line
of platinum-based therapy and have an ECOG PS of st
Poster Session; June 3, 2024
Presenter: Taofeek K. Owonikoko
Key inclusion Criteria Dual primary efficacy endpoints:
Relapsed SCLC ‘ORR per RECIST v1.1 by BICR
Received 1 prior line of platinum-based and OS
therapy 2
ECOG PS 0, 1 ‘Secondary efficacy endpoints:
Patients with asymptomatic brain metastases 4 ‘ORR per investigator; PFS; DoR,
are eligible DCR and time to response by BICR
and investigator, and PROS
statieation: TPC (topotecan,
CTF after AL therapy (<90 vs 290 days) amrubicin, of Safety endpoints:
TPC (topotecan vs amrubicin vs lurbinectedin TEAES, deaths, serious TEAES,
lurbinectedin) and TEAES leading to dose
Prior treatment with PD-(L)1 (yes vs no) 234 ‘modification or discontinuation
a ono ren Study treatment continues unt disease progression
etoringes (res veo) unacoeptable toxicity, withdrawal of consent, death,
loss to follow-up, or other reasons per protocol
+ A phase 2 study (NCT05280470) of patients with 2L or 3L ES-SCLC is also currently ongoing
1.Owonikoko T et al. ASCO 2024. Abstract TPSB126, PeerView.com
PeerView.com/HXN827 Copyright © 2000-2024, Peerview
ABBV-706: SEZ6-Targeting ADC’
+ SEZ6-targeting antibody, conjugated to a topoisomerase 1 inhibitor (Topti) payload with sub-nM cytotoxic activity
+ Drug-to-antibody ratio of 6 with stable attachment via a valine-alanine cathepsin cleavable linker
+ Phase 1, open-label, multicenter, dose-escalation and dose-expansion study
(NCT05599984) of ABBV-706 as monotherapy and in combination with
budigalimab (anti-PD-1 inhibitor), carboplatin, or cisplatin
Monotherapy Study Design
TS 2
Ke Part 1: ABBV-706 m
5226 antbody
ABBV-706 Mechanism of Action
jotherapy dose escalation
60 overall)
Part 2a: Dose optimization; Xe Part 2b: Doss expansion
22 randomized dose levels at RP2D
Part 4: ABBV-706 monotherapy dose expansion]
Part 4a: Dose expansion Part 4b: Dose expansion
in CNS tumors (n = 40) in high-grade NENS (n = 40)
CE current anaiysis (2 ongoina parts
1. Chandana SR et al ASCO 2024, Abstract 300, PeerView.com
PeerView.com/HXN827 Copyright © 2000-2024, PeerView
+ SEZ6-targeting antibody, conjugated to a topoisomerase 1 inhibitor (Topti) payload with sub-nM cytotoxic activity
+ Drug-to-antibody ratio of 6 with stable attachment via a valine-alanine cathepsin cleavable linker
+ Phase 1, open-label, multicenter, dose-escalation and dose-expansion study
(NCT05599984) of ABBV-706 as monotherapy and in combination with
budigalimab (anti-PD-1 inhibitor), carboplatin, or cisplatin
Monotherapy Study Design
TS 2
Ke Part 1: ABBV-706 m
5226 antbody
ABBV-706 Mechanism of Action
jotherapy dose escalation
60 overall)
Part 2a: Dose optimization; Xe Part 2b: Doss expansion
22 randomized dose levels at RP2D
Part 4: ABBV-706 monotherapy dose expansion]
Part 4a: Dose expansion Part 4b: Dose expansion
in CNS tumors (n = 40) in high-grade NENS (n = 40)
CE current anaiysis (2 ongoina parts
1. Chandana SR et al ASCO 2024, Abstract 300, PeerView.com
PeerView.com/HXN827 Copyright © 2000-2024, PeerView
ABBV-706: SEZ6-Targeting ADC’
ABBV-706 is highly efficacious across doses in R/R SCLC (n = 23)
Change in Target Lesion Size by Dose
2? Outcome SCLC (
E CORRS, n(%) 14 (60.9)
q (90% exact CI) (417-778)
3 Best response, n (%)
Bx CR o
8 PR 14.609)
£ so 7804)
go PD 2(87)
a CBRE, n (%) 21013)
i ll (90% exact CI) 51-984)
= + 21123 patients with SCLC were 3L+ at study
enrolment
ongoing + 11/18 patients with available 1L CTFI data were
platinum resistant
Requires a CR or PR confirmed in an assessment 24 weeks later. > Response according to RECIST vi.
«Requires CR or PR confimed in an assessment 24 weeks site or SO lasing 25 weeks. a
1. Chandana SR et al ASCO 2024, Abarat 3001 PeerView.com
PeerView.com/HXN827 Copyright © 2000-2024, PeerView
ABBV-706 is highly efficacious across doses in R/R SCLC (n = 23)
Change in Target Lesion Size by Dose
2? Outcome SCLC (
E CORRS, n(%) 14 (60.9)
q (90% exact CI) (417-778)
3 Best response, n (%)
Bx CR o
8 PR 14.609)
£ so 7804)
go PD 2(87)
a CBRE, n (%) 21013)
i ll (90% exact CI) 51-984)
= + 21123 patients with SCLC were 3L+ at study
enrolment
ongoing + 11/18 patients with available 1L CTFI data were
platinum resistant
Requires a CR or PR confirmed in an assessment 24 weeks later. > Response according to RECIST vi.
«Requires CR or PR confimed in an assessment 24 weeks site or SO lasing 25 weeks. a
1. Chandana SR et al ASCO 2024, Abarat 3001 PeerView.com
PeerView.com/HXN827 Copyright © 2000-2024, PeerView
TROP2 Overexpression in Lung Cancer!
+ High TROP2 expression has been reported in 18% of high-grade neuroendocrine tumors
from lung cancer patients (including ~10% of SCLC samples)
HGNET HGNET
High TROP2 expression (n= 21)
‘Survival Probability
TROP2 Intensity 1 TROP2 ta 2 °
intunor cots tom patents wih ing
luton of membranous TROP? expresion
"A TROP2 tent © negate), TROPE teat Y (weak o moderate), Lung Cancer-Specific Survival, mo
(ong)
+ In HGNETs, TROP2 expression was associated with lung cancer-specific survival and OS
TROP? is an attractive target for new lung cancer therapies
1. Inamura K et al Oncotarget, 2017:8:28724-28735. PeerView.com
PeerView.com/HXN827 Copyright © 2000-2024, PeerView
+ High TROP2 expression has been reported in 18% of high-grade neuroendocrine tumors
from lung cancer patients (including ~10% of SCLC samples)
HGNET HGNET
High TROP2 expression (n= 21)
‘Survival Probability
TROP2 Intensity 1 TROP2 ta 2 °
intunor cots tom patents wih ing
luton of membranous TROP? expresion
"A TROP2 tent © negate), TROPE teat Y (weak o moderate), Lung Cancer-Specific Survival, mo
(ong)
+ In HGNETs, TROP2 expression was associated with lung cancer-specific survival and OS
TROP? is an attractive target for new lung cancer therapies
1. Inamura K et al Oncotarget, 2017:8:28724-28735. PeerView.com
PeerView.com/HXN827 Copyright © 2000-2024, PeerView
IMMU-132-01: Summary of Efficacy
With Sacituzumab Govitecan!
Cohort ORR, % Median DOR, mo Median PFS,mo Median OS, mo
(95% Cl) (95% Cl)
mTNBC 108 33 77 5.5 (4.1-6.3) 13 (14.2-13,7)
HR#/HER2- MBC 54 31 87 5.5 (3.6-7.6) 12 (9.0-18.2)
mUC 45 31 129 6.8 (3.6-9.7) 16.8 (9.0-21.9)
NSCLC 54 17 6 5.2(3.2-7.1) 9.5 (5.9-16.7)
SCLC 62 18 7 e 1(5.6-
( Sacituzumab govitecan demonstrated efficacy in this pretreated patient population ]
4. Bardia À et al. Ann Oncol 2021:32:746-756 PeerView.com
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With Sacituzumab Govitecan!
Cohort ORR, % Median DOR, mo Median PFS,mo Median OS, mo
(95% Cl) (95% Cl)
mTNBC 108 33 77 5.5 (4.1-6.3) 13 (14.2-13,7)
HR#/HER2- MBC 54 31 87 5.5 (3.6-7.6) 12 (9.0-18.2)
mUC 45 31 129 6.8 (3.6-9.7) 16.8 (9.0-21.9)
NSCLC 54 17 6 5.2(3.2-7.1) 9.5 (5.9-16.7)
SCLC 62 18 7 e 1(5.6-
( Sacituzumab govitecan demonstrated efficacy in this pretreated patient population ]
4. Bardia À et al. Ann Oncol 2021:32:746-756 PeerView.com
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IMMU-132-01 SCLC: Tumor Response to Treatment
and Survival Outcomes’
All Patients 10 mg/kg
Clinical Outcome Gach aa Fee)
Median time to onset of ORR, n (%) 7 (14) 6 (17)
response was 2 months
(range: 1.8-3.6) CR, n (%) 0 0
Two response (PRs) were
still ongoing 7.2+ months PR, n 66) 7,(14) 6 (17)
and 8.7+ months after
sacituzumab govitecan Median DOR, mo (95% Cl) 5.7 (36-199) 4(3.6-5.7)
initiation
0
SD was the bestresponse | CBR (CR + PR + SD 24 mo), n (%) 17 (34) 14 (39)
in 422 01 patients Median PFS, mo (95% Cl) 3.7 (21-43) 3.7 (2.85.3)
Median OS, mo (95% Cl) 7.5 (6.288) 6.2(5.0-8.3)
1. Gray JE etal. Cin Cancer Res. 2017:29:5711-5719. PeerView.com
PeerView.com/HXN827 Copyright © 2000-2024, Peerview
and Survival Outcomes’
All Patients 10 mg/kg
Clinical Outcome Gach aa Fee)
Median time to onset of ORR, n (%) 7 (14) 6 (17)
response was 2 months
(range: 1.8-3.6) CR, n (%) 0 0
Two response (PRs) were
still ongoing 7.2+ months PR, n 66) 7,(14) 6 (17)
and 8.7+ months after
sacituzumab govitecan Median DOR, mo (95% Cl) 5.7 (36-199) 4(3.6-5.7)
initiation
0
SD was the bestresponse | CBR (CR + PR + SD 24 mo), n (%) 17 (34) 14 (39)
in 422 01 patients Median PFS, mo (95% Cl) 3.7 (21-43) 3.7 (2.85.3)
Median OS, mo (95% Cl) 7.5 (6.288) 6.2(5.0-8.3)
1. Gray JE etal. Cin Cancer Res. 2017:29:5711-5719. PeerView.com
PeerView.com/HXN827 Copyright © 2000-2024, Peerview
ADCs in SCLC: Conclusions and Considerations
+ In a tumor without easily targetable mutations, targeting surface proteins
with ADCs is an attractive approach > preliminary promising results
with several agents
+ Need to determine the best characteristics: potency, payload, DAR,
linker stability/ cleavage, toxicity, bystander effect
+ Important to learn to recognize and manage ADC toxicities (eg, ILD, Gl,
myelosuppression, ocular, mucositis, other)
PeerView.com
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+ In a tumor without easily targetable mutations, targeting surface proteins
with ADCs is an attractive approach > preliminary promising results
with several agents
+ Need to determine the best characteristics: potency, payload, DAR,
linker stability/ cleavage, toxicity, bystander effect
+ Important to learn to recognize and manage ADC toxicities (eg, ILD, Gl,
myelosuppression, ocular, mucositis, other)
PeerView.com
PeerView.com/HXN827 Copyright © 2000-2024, PeerView
Expert Panel Discussion
Copyright © 2000-2024, PeerView
Copyright © 2000-2024, PeerView
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