Maximizing the Role of ADCs in Urothelial Carcinoma: Practical Tips for Patient Selection, Safety Management, and Collaborative Care
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Jun 25, 2024
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About This Presentation
Chair and Presenters, Petros Grivas, MD, PhD, Evan Y. Yu, MD, and Tian Zhang, MD, MHS, discuss bladder cancer in this CME/MOC/NCPD/AAPA/IPCE activity titled “Maximizing the Role of ADCs in Urothelial Carcinoma: Practical Tips for Patient Selection, Safety Management, and Collaborative Care.” For...
Slide Content
Maximizing the Role of ADCs
in Urothelial Carcinoma
Practical Tips for Patient Selection, Safety Management,
and Collaborative Care
Petros Grivas, MD, PhD
Professor
Division of Hematology and Oncology, Department of Medicine | ig
Clinical Director, Genitourinary Cancers Program WES Tian Zhang, MD, MHS
University of Washington School of Medicine ig Associate Professor, Division
Professor, Clinical Research Division of Hematology and Oncology
Fred Hutchinson Cancer Center Department of Internal Medicine
Seattle, Washington Associate Director for Clinical Research
Evan Y. Yu, MD Harold C. Simmons
Section Head, Medical Oncology, Clinical Research Division ee a
Fred Hutchinson Cancer Center wt exes)
Medical Director, Clinical Research Support PSS Dallas, Texas
Fred Hutchinson Cancer Research Consortium ÉL $ 4
Professor of Medicine 7 À
Division of Hematology and Oncology, Department of Medicine
University of Washington School of Medicine
Seattle, Washington
Go online to access full CME/MOC/NCPD/AAPA/IPCE information, including faculty disclosures.
Copyright © 2000-2024, Peerview
in Urothelial Carcinoma
Practical Tips for Patient Selection, Safety Management,
and Collaborative Care
Petros Grivas, MD, PhD
Professor
Division of Hematology and Oncology, Department of Medicine | ig
Clinical Director, Genitourinary Cancers Program WES Tian Zhang, MD, MHS
University of Washington School of Medicine ig Associate Professor, Division
Professor, Clinical Research Division of Hematology and Oncology
Fred Hutchinson Cancer Center Department of Internal Medicine
Seattle, Washington Associate Director for Clinical Research
Evan Y. Yu, MD Harold C. Simmons
Section Head, Medical Oncology, Clinical Research Division ee a
Fred Hutchinson Cancer Center wt exes)
Medical Director, Clinical Research Support PSS Dallas, Texas
Fred Hutchinson Cancer Research Consortium ÉL $ 4
Professor of Medicine 7 À
Division of Hematology and Oncology, Department of Medicine
University of Washington School of Medicine
Seattle, Washington
Go online to access full CME/MOC/NCPD/AAPA/IPCE information, including faculty disclosures.
Copyright © 2000-2024, Peerview
Disclosures
All relevant conflicts of interest have been mitigated prior to the commencement of
the activity.
Chair/Planner
Petros Grivas, MD, PhD
Professor
Division of Hematology and Oncology, Department
of Medicine
Clinical Director, Genitourinary Cancers Program
University of Washington School of Medicine
Professor, Clinical Research Division
Fred Hutchinson Cancer Center
Seattle, Washington
Petros Grivas, MD, PhD, has a financial
interest/relationship or affiliation in the form of:
Consultant and/or Advisor for Aadi Bioscience, Inc.;
AbbVie Inc.; Asieris Pharmaceuticals; Astellas
Pharma Inc.; AstraZeneca; BostonGene Corporation;
PeerView.com/MBD827
Bristol Myers Squibb; CG Oncology; EMD Serono; F
Hoffmann-La Roche Ltd; Fresenius Kabi US; Gilead
Sciences, Inc.; G1 Therapeutics, Inc.; ImmunityBio,
Inc.; Janssen Pharmaceuticals, Inc.; Lucence Health
Inc.; Merck & Co., Inc.; Pfizer; PureTech Healt;
Seattle Genetics, Inc.; Silverback Therapeutics; and
Strata Oncology, Inc.
Grant/Research Support from Acrivon Therapeutics;
ALX Oncology Inc.; Bristol Myers Squibb; EMD
Serono; Genentech, Inc.; Gilead Sciences, Inc.;
GlaxoSmithKline; G1 Therapeutics, Inc.; Merck &
Co. Inc.; Mirati Therapeutics, Inc.; Pfizer; and QED
Therapeutics
All relevant conflicts of interest have been mitigated prior to the commencement of
the activity.
Chair/Planner
Petros Grivas, MD, PhD
Professor
Division of Hematology and Oncology, Department
of Medicine
Clinical Director, Genitourinary Cancers Program
University of Washington School of Medicine
Professor, Clinical Research Division
Fred Hutchinson Cancer Center
Seattle, Washington
Petros Grivas, MD, PhD, has a financial
interest/relationship or affiliation in the form of:
Consultant and/or Advisor for Aadi Bioscience, Inc.;
AbbVie Inc.; Asieris Pharmaceuticals; Astellas
Pharma Inc.; AstraZeneca; BostonGene Corporation;
PeerView.com/MBD827
Bristol Myers Squibb; CG Oncology; EMD Serono; F
Hoffmann-La Roche Ltd; Fresenius Kabi US; Gilead
Sciences, Inc.; G1 Therapeutics, Inc.; ImmunityBio,
Inc.; Janssen Pharmaceuticals, Inc.; Lucence Health
Inc.; Merck & Co., Inc.; Pfizer; PureTech Healt;
Seattle Genetics, Inc.; Silverback Therapeutics; and
Strata Oncology, Inc.
Grant/Research Support from Acrivon Therapeutics;
ALX Oncology Inc.; Bristol Myers Squibb; EMD
Serono; Genentech, Inc.; Gilead Sciences, Inc.;
GlaxoSmithKline; G1 Therapeutics, Inc.; Merck &
Co. Inc.; Mirati Therapeutics, Inc.; Pfizer; and QED
Therapeutics
Disclosures
All relevant conflicts of interest have been mitigated prior to the commencement of
the activity.
Faculty/Planner
Evan Y. Yu, MD
Section Head, Medical Oncology, Clinical
Research Division
Fred Hutchinson Cancer Center
Medical Director, Clinical Research Support
Fred Hutchinson Cancer Research Consortium
Professor of Medicine
Division of Hematology and Oncology, Department
of Medicine
University of Washington School of Medicine
Seattle, Washington
PeerView.com/MBD827
Evan Y. Yu, MD, has a financial interest/relationship
or affiliation in the form of:
Consultant and/or Advisor for AADI bioscience;
Advanced Accelerator Applications; Bayer
Corporation; Bristol Myers Squibb; Janssen
Pharmaceuticals, Inc.; Lantheus; Loxo Oncology;
Merck & Co., Inc.; and Oncternal Therapeutics.
Grant/Research Support from Bayer Corporation;
Blue Earth Diagnostics; Dendreon Pharmaceuticals
LLC; Lantheus; Merck & Co., Inc.; Oncternal
Therapeutics; Seagen Inc.; and Tyra Biosciences, Inc.
All relevant conflicts of interest have been mitigated prior to the commencement of
the activity.
Faculty/Planner
Evan Y. Yu, MD
Section Head, Medical Oncology, Clinical
Research Division
Fred Hutchinson Cancer Center
Medical Director, Clinical Research Support
Fred Hutchinson Cancer Research Consortium
Professor of Medicine
Division of Hematology and Oncology, Department
of Medicine
University of Washington School of Medicine
Seattle, Washington
PeerView.com/MBD827
Evan Y. Yu, MD, has a financial interest/relationship
or affiliation in the form of:
Consultant and/or Advisor for AADI bioscience;
Advanced Accelerator Applications; Bayer
Corporation; Bristol Myers Squibb; Janssen
Pharmaceuticals, Inc.; Lantheus; Loxo Oncology;
Merck & Co., Inc.; and Oncternal Therapeutics.
Grant/Research Support from Bayer Corporation;
Blue Earth Diagnostics; Dendreon Pharmaceuticals
LLC; Lantheus; Merck & Co., Inc.; Oncternal
Therapeutics; Seagen Inc.; and Tyra Biosciences, Inc.
Disclosures
All relevant conflicts of interest have been mitigated prior to the commencement of
the activity.
Faculty/Planner
Tian Zhang, MD, MHS
Associate Professor, Division of Hematology
and Oncology
Department of Internal Medicine
Associate Director for Clinical Research
Harold C. Simmons Comprehensive Cancer Center
UT Southwestern Medical Center
Dallas, Texas
Tian Zhang, MD, MHS, has a financial
interest/relationship or affiliation in the form of:
Consultant and/or Advisor for Amgen Inc.; Aptitude
Health; Aravive; AstraZeneca; AVEO
Pharmaceuticals, Inc.; Bayer Corporation;
PeerView.com/MBD827
Bristol Myers Squibb; Eisai Inc.; EMD Serono;
Exelixis, Inc.; Gilead Sciences, Inc.; Janssen
Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; MJH
LIFE SCIENCES®; Novartis Pharmaceuticals
Corporation; Pfizer Inc.; and Sanofi-Aventis
Grant/Research Support from ALX Oncology Inc.;
Astellas Pharma US, Inc.; AstraZeneca; Exelixis,
Inc.; Janssen Pharmaceuticals, Inc.; Janux
Therapeutics; Lilly; Merck & Co., Inc.; Pfizer Inc.;
OncoC4; and Tempus
All relevant conflicts of interest have been mitigated prior to the commencement of
the activity.
Faculty/Planner
Tian Zhang, MD, MHS
Associate Professor, Division of Hematology
and Oncology
Department of Internal Medicine
Associate Director for Clinical Research
Harold C. Simmons Comprehensive Cancer Center
UT Southwestern Medical Center
Dallas, Texas
Tian Zhang, MD, MHS, has a financial
interest/relationship or affiliation in the form of:
Consultant and/or Advisor for Amgen Inc.; Aptitude
Health; Aravive; AstraZeneca; AVEO
Pharmaceuticals, Inc.; Bayer Corporation;
PeerView.com/MBD827
Bristol Myers Squibb; Eisai Inc.; EMD Serono;
Exelixis, Inc.; Gilead Sciences, Inc.; Janssen
Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; MJH
LIFE SCIENCES®; Novartis Pharmaceuticals
Corporation; Pfizer Inc.; and Sanofi-Aventis
Grant/Research Support from ALX Oncology Inc.;
Astellas Pharma US, Inc.; AstraZeneca; Exelixis,
Inc.; Janssen Pharmaceuticals, Inc.; Janux
Therapeutics; Lilly; Merck & Co., Inc.; Pfizer Inc.;
OncoC4; and Tempus
Planning Committee and Reviewer Disclosures
Planners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education,
and Bladder Cancer Advocacy Network do not have any relevant financial relationships
related to this CE activity unless listed below.
PeerView.com/MBD827
Planners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education,
and Bladder Cancer Advocacy Network do not have any relevant financial relationships
related to this CE activity unless listed below.
PeerView.com/MBD827
Our Goals for Today
Augment your understanding of the current rationales and
evidence for the treatment of urothelial cancer with ADCs targeting
Nectin-4, Trop-2, and HER2
— Equip you with the skills you need to implement ADC regimens into
personalized treatment plans
———— Provide you with guidance on how to support team-based
management of the unique suite of adverse events associated with
various ADC-based therapies
PeerView.com/MBD827
Augment your understanding of the current rationales and
evidence for the treatment of urothelial cancer with ADCs targeting
Nectin-4, Trop-2, and HER2
— Equip you with the skills you need to implement ADC regimens into
personalized treatment plans
———— Provide you with guidance on how to support team-based
management of the unique suite of adverse events associated with
various ADC-based therapies
PeerView.com/MBD827
Shortcomings in the Real-World Management
of Advanced UC
One-quarter to one-half of patients
do not receive any treatment for
their disease13
Less than half of patients who progress
on 1L therapy receive 2L therapy’
Post-immunotherapy treatments Less than one-third of patients
often include chemotherapy or a who discontinue PD-1/L1 inhibitor
different immune checkpoint inhibitor therapy receive subsequent
rather than a novel agent:+ therapy in the 2L or 3L4
Patients are not achieving the outcomes
modern therapy is capable of providing
4. Morgans AK. ESMO 2021. Abstract 7O4P. 2 en Met al. ESMO 2021. Abstract 701P. 3. app Za al. J Manag Care Spec Pharm. 2021-27240-2. rn
4. Morgans AK ot al. J Clin Oncol 2021:39(suppI6)414.5. Beig A at al. Curr Oncol2021:28:9812:9824. 6. Simeone JC et al. Cancer Epidemiol. 2019;60:121-127. Peer View.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
of Advanced UC
One-quarter to one-half of patients
do not receive any treatment for
their disease13
Less than half of patients who progress
on 1L therapy receive 2L therapy’
Post-immunotherapy treatments Less than one-third of patients
often include chemotherapy or a who discontinue PD-1/L1 inhibitor
different immune checkpoint inhibitor therapy receive subsequent
rather than a novel agent:+ therapy in the 2L or 3L4
Patients are not achieving the outcomes
modern therapy is capable of providing
4. Morgans AK. ESMO 2021. Abstract 7O4P. 2 en Met al. ESMO 2021. Abstract 701P. 3. app Za al. J Manag Care Spec Pharm. 2021-27240-2. rn
4. Morgans AK ot al. J Clin Oncol 2021:39(suppI6)414.5. Beig A at al. Curr Oncol2021:28:9812:9824. 6. Simeone JC et al. Cancer Epidemiol. 2019;60:121-127. Peer View.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
Antibody-Drug Conjugates’?
+ Consist of a monoclonal antibody (mAb)-antigen
(target) pair, a cytotoxin (payload), and a linker
molecule that joins the two together Linker
+ Contrasts with conventional chemotherapies that
are nontargeted and nonspecific; increases the
therapeutic index of cytotoxic agents and
enhances safety by reducing off-target effects
+ Pharmacodynamic properties of ADCs make ADC
them uniquely suited in treatment-refractory
Highly specific binding properties of mAbs
enable the selective targeting and delivery of
potent cytotoxic agents to tumors
cancers, which have a high degree of
intertumor and intratumor heterogeneity and
hypoxic and immunosuppressive TMEs?
1. Drago JZ et al. Nat Rov Cin Oncol, 2021:18:827-344, 2. Coats Seta. Cin Cancor Ros. 201925:5441-5448.
PeerView.com/MBD827
Monoclonal
antibody
Cancer cell
PeerView.com
Copyright © 2000-2024, PeerView
+ Consist of a monoclonal antibody (mAb)-antigen
(target) pair, a cytotoxin (payload), and a linker
molecule that joins the two together Linker
+ Contrasts with conventional chemotherapies that
are nontargeted and nonspecific; increases the
therapeutic index of cytotoxic agents and
enhances safety by reducing off-target effects
+ Pharmacodynamic properties of ADCs make ADC
them uniquely suited in treatment-refractory
Highly specific binding properties of mAbs
enable the selective targeting and delivery of
potent cytotoxic agents to tumors
cancers, which have a high degree of
intertumor and intratumor heterogeneity and
hypoxic and immunosuppressive TMEs?
1. Drago JZ et al. Nat Rov Cin Oncol, 2021:18:827-344, 2. Coats Seta. Cin Cancor Ros. 201925:5441-5448.
PeerView.com/MBD827
Monoclonal
antibody
Cancer cell
PeerView.com
Copyright © 2000-2024, PeerView
Download the
Practice Aid to
learn more
about ADCs
ADC Mechanism of Action!
Antibody engagement leads ADC. alize o Sem ale
een antlumaractviy j Most ADCs are internalized in tumor cell Membrane-permeable payloads enter
Via several mechanisms: from endosomes neighboring cells, regardless of target
1. Fe-mediated stimulation of immune cel and/or lysosomes and takes its effect on ‘pression, and can also kill the:
2. Disruption of receptor dimerization cells, leading to cell death (bystander effect)
+ = Femedated
stmulaton Pol
‘of immune ELA
are JL | Ses, Ah
N
el
of ma
‘signaling
Tumor cell
1. Drago JZ tal. Nat Rev Cin Oncol. 2021:18:327-344. PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
Practice Aid to
learn more
about ADCs
ADC Mechanism of Action!
Antibody engagement leads ADC. alize o Sem ale
een antlumaractviy j Most ADCs are internalized in tumor cell Membrane-permeable payloads enter
Via several mechanisms: from endosomes neighboring cells, regardless of target
1. Fe-mediated stimulation of immune cel and/or lysosomes and takes its effect on ‘pression, and can also kill the:
2. Disruption of receptor dimerization cells, leading to cell death (bystander effect)
+ = Femedated
stmulaton Pol
‘of immune ELA
are JL | Ses, Ah
N
el
of ma
‘signaling
Tumor cell
1. Drago JZ tal. Nat Rev Cin Oncol. 2021:18:327-344. PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
BCAN Is an Excellent Resource for
Professionals, Patients, and Care Partners
When diagnosed with bladder cancer,
MY patients and their care partners may feel
7 overwhelmed by the amount of treatment
BCAN. tion for urothelial carcinoma. BCAN
een provides educational resources to help
‘todo ere once i We give blade! Patient
patients feel more prepared. a vert the rt and
‘support they need to.cope with
the disease.
In addition to giving patients and care partners support to cope with
the disease, BCAN also offers free resources for healthcare
providers to share with patients:
+ Printed materials + Podcasts + Bladder Cancer Support Line:
+ Animated videos + Treatment matrix call (833-ASK-4-BCA)
+ Webinars * Clinical trials dashboard
See the BCAN Practice Aid for full details on
the BCAN website, a QR code for professionals
to download resources for patients, and more!
PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
Professionals, Patients, and Care Partners
When diagnosed with bladder cancer,
MY patients and their care partners may feel
7 overwhelmed by the amount of treatment
BCAN. tion for urothelial carcinoma. BCAN
een provides educational resources to help
‘todo ere once i We give blade! Patient
patients feel more prepared. a vert the rt and
‘support they need to.cope with
the disease.
In addition to giving patients and care partners support to cope with
the disease, BCAN also offers free resources for healthcare
providers to share with patients:
+ Printed materials + Podcasts + Bladder Cancer Support Line:
+ Animated videos + Treatment matrix call (833-ASK-4-BCA)
+ Webinars * Clinical trials dashboard
See the BCAN Practice Aid for full details on
the BCAN website, a QR code for professionals
to download resources for patients, and more!
PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
Targeting Nectin-4
ADC Therapy for Metastatic
Urothelial Cancer
Tian Zhang, MD, MHS
Associate Professor, Division of Hematology and Oncology
Department of Internal Medicine
Associate Director for Clinical Research
Harold C. Simmons Comprehensive Cancer Center
UT Southwestern Medical Center
Dallas, Texas
G
Y yy
Copyright © 2000-2024, PeerView
ADC Therapy for Metastatic
Urothelial Cancer
Tian Zhang, MD, MHS
Associate Professor, Division of Hematology and Oncology
Department of Internal Medicine
Associate Director for Clinical Research
Harold C. Simmons Comprehensive Cancer Center
UT Southwestern Medical Center
Dallas, Texas
G
Y yy
Copyright © 2000-2024, PeerView
Nectin-4: Target for ADC Therapy in
Advanced/Metastatic UC'?
+ Nectin and nectin-like proteins constitute
a family of adhesion molecules with key
roles in cell polarity, proliferation,
differentiation, and migration in epithelial,
endothelial, immune, and nervous
systems
Nectin-4 protein is overexpressed in
Bladder cancer
several tumors, particularly in breast and
urothelial cancer, and is associated with a
poor prognosis
Nectin-4 expression in normal tissue is
Breast cancer
Nec. expresen in human cancer pan specimens. Representative FFPE
imi il i i IHC for nectin-4 are shown. insitional bladder
limited, rendering it a valuable target in a andy Be reed a on eee
epithelial cancers including UC ‘expression. C, breast carcinoma with strong expression. D, breast carcinoma
‘with moderate expression.
1. Heath El, Rosenberg JE. Nat Rev Urol 2021:18:99-103. 2. Chala-E Petal. Concer Ros. 2016:76:3009-3013. PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
Advanced/Metastatic UC'?
+ Nectin and nectin-like proteins constitute
a family of adhesion molecules with key
roles in cell polarity, proliferation,
differentiation, and migration in epithelial,
endothelial, immune, and nervous
systems
Nectin-4 protein is overexpressed in
Bladder cancer
several tumors, particularly in breast and
urothelial cancer, and is associated with a
poor prognosis
Nectin-4 expression in normal tissue is
Breast cancer
Nec. expresen in human cancer pan specimens. Representative FFPE
imi il i i IHC for nectin-4 are shown. insitional bladder
limited, rendering it a valuable target in a andy Be reed a on eee
epithelial cancers including UC ‘expression. C, breast carcinoma with strong expression. D, breast carcinoma
‘with moderate expression.
1. Heath El, Rosenberg JE. Nat Rev Urol 2021:18:99-103. 2. Chala-E Petal. Concer Ros. 2016:76:3009-3013. PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
Enfortumab Vedotin, a Nectin-4—Directed ADC1-3
Consists of a human anti-Nectin-4
antibody conjugated to the anti-mitotic
agent monomethyl auristatin E (MMAE)
Binds to Nectin-4 on the surface of tumor
cells, followed by internalization by
endocytosis and release of MMAE after
lysosomal degradation
MMAE disrupts microtubules and induces
apoptosis of the tumor cell
Additional antitumor effects mediated
through antibody-dependent cellular
cytotoxicity, and complement-dependent
cytotoxicity
4. Chat Peta. Cancr Ros. 201676:3003:9013. 2. Hanna KS. Drugs. 20202017. er
3. Padcov (enlotumab vodoln) Prescning information. sw accossdata Ida govn.gsatida_0cs1ab0120237761 1975024502501 pt PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
Consists of a human anti-Nectin-4
antibody conjugated to the anti-mitotic
agent monomethyl auristatin E (MMAE)
Binds to Nectin-4 on the surface of tumor
cells, followed by internalization by
endocytosis and release of MMAE after
lysosomal degradation
MMAE disrupts microtubules and induces
apoptosis of the tumor cell
Additional antitumor effects mediated
through antibody-dependent cellular
cytotoxicity, and complement-dependent
cytotoxicity
4. Chat Peta. Cancr Ros. 201676:3003:9013. 2. Hanna KS. Drugs. 20202017. er
3. Padcov (enlotumab vodoln) Prescning information. sw accossdata Ida govn.gsatida_0cs1ab0120237761 1975024502501 pt PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
EV-301: Enfortumab Vedotin in Pretreated Locally Advanced
or Metastatic Urothelial Carcinoma’
Phase 3
Adult patients with locally
advanced or mU!
ECOG PS
Prior platinum-containing
hemotherapy
PD during or after
ckpoint inhibitor
treatment
+ Primary endpoint: OS
Enfortumab vedotin
mg/kg IV over 30 min
on d 1, 8, and 15 of each
28-d cycle
Investigator's choice:
docetaxel, paclitaxel, or
vinflunine (European Union only)
+ Secondary endpoints: PFS, DOR, ORR, safety/tolerability, QOL
1. Mps-cinicarias gowet2/showNCTO3474107. 2. Powis Tet al. N Eng J Mod, 2021:384:1125-1135.
PeerView.com/MBD827
+ Treatment until radiologic
progression, intolerance,
or other discontinuation
criterion met
Radiologic assessment of
tumor response status at
baseline and every 8 wk
PeerView.com
Copyright © 2000-2024, PeerView
or Metastatic Urothelial Carcinoma’
Phase 3
Adult patients with locally
advanced or mU!
ECOG PS
Prior platinum-containing
hemotherapy
PD during or after
ckpoint inhibitor
treatment
+ Primary endpoint: OS
Enfortumab vedotin
mg/kg IV over 30 min
on d 1, 8, and 15 of each
28-d cycle
Investigator's choice:
docetaxel, paclitaxel, or
vinflunine (European Union only)
+ Secondary endpoints: PFS, DOR, ORR, safety/tolerability, QOL
1. Mps-cinicarias gowet2/showNCTO3474107. 2. Powis Tet al. N Eng J Mod, 2021:384:1125-1135.
PeerView.com/MBD827
+ Treatment until radiologic
progression, intolerance,
or other discontinuation
criterion met
Radiologic assessment of
tumor response status at
baseline and every 8 wk
PeerView.com
Copyright © 2000-2024, PeerView
EV-301: Enfortumab Vedotin in Refractory mUC12.2
= A]
Enfortumab > DEEE TE IT TT]
os » Cremas 1007 097 8051070)
x Um 70 0)
à
Target: Nectin-4, a type 1 a E
transmembrane cell adhesion 0 nfortumab vedotin
molecule overexpressed in =
epithelial cancers
Linker: protease cleavable
Payload: MMAE
Chemotherapy
ERZIELT
Durston ot 0S. me
Exloramabvedotn 301 206 22 257 246 ZU 22 190 59 m 105 05 6) $2 2 DD 7
Cramer _ 20 20 ZU 250 20 219.98 10 MI UM sı um m
RESPETE RE EE]
“ AA
2020: FDA approved » a as
40 ¡rl
'ORR higher with EV vs chemo: Eo Pom
41% vs 18%; P < .001 >
Enfortumab vedotin
24-mo outcomes support
a x e Chemotherapy
initial results‘ (REREENERENENEEEEEETEE
Mo, ot (Duration of PES, mo.
sia au Elo vedoón 301 260 224 208 105 158 102 9 m 58 m DT NT 5 2
Du EHI III rw 18 1 ek à à 1 0
1. Pontes Total. N Eng! J Med. 2021:384:1125-1136. 2. Padcev enfotuma vodotin) Prescrbing Information À
tps ww accossdata Ida govierugsaida_ docslabel2023/761 137802450250 pdf. 3. Rosenberg et al. ASCO 2022. Abstract 4516. PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
= A]
Enfortumab > DEEE TE IT TT]
os » Cremas 1007 097 8051070)
x Um 70 0)
à
Target: Nectin-4, a type 1 a E
transmembrane cell adhesion 0 nfortumab vedotin
molecule overexpressed in =
epithelial cancers
Linker: protease cleavable
Payload: MMAE
Chemotherapy
ERZIELT
Durston ot 0S. me
Exloramabvedotn 301 206 22 257 246 ZU 22 190 59 m 105 05 6) $2 2 DD 7
Cramer _ 20 20 ZU 250 20 219.98 10 MI UM sı um m
RESPETE RE EE]
“ AA
2020: FDA approved » a as
40 ¡rl
'ORR higher with EV vs chemo: Eo Pom
41% vs 18%; P < .001 >
Enfortumab vedotin
24-mo outcomes support
a x e Chemotherapy
initial results‘ (REREENERENENEEEEEETEE
Mo, ot (Duration of PES, mo.
sia au Elo vedoón 301 260 224 208 105 158 102 9 m 58 m DT NT 5 2
Du EHI III rw 18 1 ek à à 1 0
1. Pontes Total. N Eng! J Med. 2021:384:1125-1136. 2. Padcev enfotuma vodotin) Prescrbing Information À
tps ww accossdata Ida govierugsaida_ docslabel2023/761 137802450250 pdf. 3. Rosenberg et al. ASCO 2022. Abstract 4516. PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
EV-301 Long-Term Outcomes’
os PFS
Event, NIN___ Median (95% Ci
Event, NN __ Median (95% CI)
e man — 207801 1281 (1101182) Eran — za 65632820)
Chemoterpy ZUM 8248251025) Chemoherapy 20T 37152390
® ®
7° HR = 0.74 (95% Cl, 0.581-0.852) q” HR = 0.632 (95% CI. 0.525-0.762)
E One sed P= 00015 I One sided P 00001
ie E
© = Enfortumab vedotin
Chemoiherpy Chemotherapy
Duration of Overall Survival, mo Duration of Progression Free Survival, mo
After a median follow-up of ~2 years, enfortumab vedotin maintained a clinically meaningful OS benefit versus
chemotherapy, consistent results from the primary analysis; PFS and ORR also remained consistent
1. Rosenberg JE et al. Ann Oncol, 2023:34:1047-1054. PeerView.com
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os PFS
Event, NIN___ Median (95% Ci
Event, NN __ Median (95% CI)
e man — 207801 1281 (1101182) Eran — za 65632820)
Chemoterpy ZUM 8248251025) Chemoherapy 20T 37152390
® ®
7° HR = 0.74 (95% Cl, 0.581-0.852) q” HR = 0.632 (95% CI. 0.525-0.762)
E One sed P= 00015 I One sided P 00001
ie E
© = Enfortumab vedotin
Chemoiherpy Chemotherapy
Duration of Overall Survival, mo Duration of Progression Free Survival, mo
After a median follow-up of ~2 years, enfortumab vedotin maintained a clinically meaningful OS benefit versus
chemotherapy, consistent results from the primary analysis; PFS and ORR also remained consistent
1. Rosenberg JE et al. Ann Oncol, 2023:34:1047-1054. PeerView.com
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Phase 1/2 EV-103: Enfortumab Vedotin With or Without
Pembrolizumab in Cisplatin-Ineligible Patients’
Local
séances
ar Cohort K Patient Demographics
Dose Escalation 7
een Characteristic (rity nara) COTES RIRE
iat nage = =73) : | (
ty Sex, male, No.(%) 54(711) 56(767) Metastasis disease sites No. (%)
y Age, years, median — 74 64.01) 74 (66-60) PO"? 19(250) — 21(288)
A (range) Liver 13(17.1) 13(178)
EV + pembrolizumab — [Caron A Race, White, No. (%) 61 (80.3) 55 (75.3) Lung 37 (48.7) 30 (41.1)
pare DER: ECOG PS, No. (%) Metastasis category, No. (%)
(40) o 33(43.4) 28 (98.4) Lymph node only 10(132) — 12(164)
1 33(434) 35479) Visceral disease 64 (64.2) 601822)
fem 2 10432) 10087) Not applicable 206) 114)
irae Primary tumor location PD-L1 status by CPS, No. (%)
bat ineighie No. (%) CPS <10 44(57.9) 38(52.1)
Lower tract 46(60.5) 51(69.9) CPS 210 31(408) 28(384)
Upper tract 30 (39.5) 21 (28.8) Not evaluable 14.3) 79.6)
1. itps/cincalals.govet2/showNCT03288545.2. Holmes CJ et al. J Cin Oncol. 2023:41:22:31. 3. O'Donnell PH et al. J Ci Oncol, 2023:41:4107-4117. PeerView.com
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Pembrolizumab in Cisplatin-Ineligible Patients’
Local
séances
ar Cohort K Patient Demographics
Dose Escalation 7
een Characteristic (rity nara) COTES RIRE
iat nage = =73) : | (
ty Sex, male, No.(%) 54(711) 56(767) Metastasis disease sites No. (%)
y Age, years, median — 74 64.01) 74 (66-60) PO"? 19(250) — 21(288)
A (range) Liver 13(17.1) 13(178)
EV + pembrolizumab — [Caron A Race, White, No. (%) 61 (80.3) 55 (75.3) Lung 37 (48.7) 30 (41.1)
pare DER: ECOG PS, No. (%) Metastasis category, No. (%)
(40) o 33(43.4) 28 (98.4) Lymph node only 10(132) — 12(164)
1 33(434) 35479) Visceral disease 64 (64.2) 601822)
fem 2 10432) 10087) Not applicable 206) 114)
irae Primary tumor location PD-L1 status by CPS, No. (%)
bat ineighie No. (%) CPS <10 44(57.9) 38(52.1)
Lower tract 46(60.5) 51(69.9) CPS 210 31(408) 28(384)
Upper tract 30 (39.5) 21 (28.8) Not evaluable 14.3) 79.6)
1. itps/cincalals.govet2/showNCT03288545.2. Holmes CJ et al. J Cin Oncol. 2023:41:22:31. 3. O'Donnell PH et al. J Ci Oncol, 2023:41:4107-4117. PeerView.com
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EV-103 (Cohort K): Responses!
Confirmed ORR, No.
CR 8 (10.5) 3 (4.1)
PR 41 (53.9) 30 (41.1)
sD 17 (22.4) 25 (34.2)
PD 6 (7.9) 7 (9.6)
NE 3 (3.9) 5 (6.8)
No Assessment 1 (1.3) 3 (4.1)
Time to objective response, months, median (range) 2.07 (1.1, 6.6) 2.07 (1.9, 15.4)
Treatment cycles, No., months, median (range) 11.0 (1, 29) 8.0 (1, 33)
1. ODonnel PH eta. J Gin Oncol. 2023:41:4107-4117. PeerView.com
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Confirmed ORR, No.
CR 8 (10.5) 3 (4.1)
PR 41 (53.9) 30 (41.1)
sD 17 (22.4) 25 (34.2)
PD 6 (7.9) 7 (9.6)
NE 3 (3.9) 5 (6.8)
No Assessment 1 (1.3) 3 (4.1)
Time to objective response, months, median (range) 2.07 (1.1, 6.6) 2.07 (1.9, 15.4)
Treatment cycles, No., months, median (range) 11.0 (1, 29) 8.0 (1, 33)
1. ODonnel PH eta. J Gin Oncol. 2023:41:4107-4117. PeerView.com
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Moving to 1L, Phase 3 EV-302:
Pembrolizumab Plus EV Versus Platinum Plus Gemcitabine’
Key Eligibility Criteria
untreated
EV + pembrolizumab?
mum treatment cycles for
Stratification Haken L Treatment until
i born lisease progression
Cisplatin olay 14 perabrod ines, per BICR, clinical
+ Eligible for platinum, (clighie/ineligible) i progression,
Ev + PD-L1 expression
V, and P unacceptable
(high/low) toxicity, or
D Amia + Liver metastases Chemotherapy* completion of
(presentiabsent) (cisplatin or carboplatin + maximum cycles
SP:
gemcitabine)
Maximum 6 cycles
+ Dual primary endpoints: PFS by BICR and OS
+ Select secondary endpoints: ORR per RECIST v1.1 by BICR
and investigator assessment, safety
Statistical plan for analysis: the fst planned analysis was performed ar approximately 526 PFS (nal) and 356 OS events (interim: if OS was postive at interim
the OS intr analysis was considered final. Data cutot August 8, 2023; FP: Apr 7, 2020; LI: November 8, 2022. Cisplatin eigiblty and assignmentidosing of
plat vs carboplatin were protocol-defined: patents received 3-uk cycles of EV 1.25 mg/kg IV on days 1 and 8 and pembrolzumab 200 mg IV on day 1
‘Maintenance therapy could be used folowing completion andlor discontinuation of platinum-containing therapy.
1. Podes Total N Engl J Mod 2024:300:878-888.
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Pembrolizumab Plus EV Versus Platinum Plus Gemcitabine’
Key Eligibility Criteria
untreated
EV + pembrolizumab?
mum treatment cycles for
Stratification Haken L Treatment until
i born lisease progression
Cisplatin olay 14 perabrod ines, per BICR, clinical
+ Eligible for platinum, (clighie/ineligible) i progression,
Ev + PD-L1 expression
V, and P unacceptable
(high/low) toxicity, or
D Amia + Liver metastases Chemotherapy* completion of
(presentiabsent) (cisplatin or carboplatin + maximum cycles
SP:
gemcitabine)
Maximum 6 cycles
+ Dual primary endpoints: PFS by BICR and OS
+ Select secondary endpoints: ORR per RECIST v1.1 by BICR
and investigator assessment, safety
Statistical plan for analysis: the fst planned analysis was performed ar approximately 526 PFS (nal) and 356 OS events (interim: if OS was postive at interim
the OS intr analysis was considered final. Data cutot August 8, 2023; FP: Apr 7, 2020; LI: November 8, 2022. Cisplatin eigiblty and assignmentidosing of
plat vs carboplatin were protocol-defined: patents received 3-uk cycles of EV 1.25 mg/kg IV on days 1 and 8 and pembrolzumab 200 mg IV on day 1
‘Maintenance therapy could be used folowing completion andlor discontinuation of platinum-containing therapy.
1. Podes Total N Engl J Mod 2024:300:878-888.
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Improved OS With
Enfortumab Vedotin Plus Pembrolizumab1
HR
- (5% cy Two-Sided P mOS (95% Cl), mo
90
80
N Ever
EV+P
442 133(80.1)
Chemo 444 226(509)
0.47
(0.38-0.
31.5 (25.
IR)
16.1 (139-183)
<.00001
70
Risk of death was reduced by
zx ® 53% in patients who received
5 50 EV + pembrolizumab
o 40
30
20
10
+ +
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32
reer Time, mo
EV+P 442 428 400 304 376 301 270 222 182 141 108 67
Chemo 444 423 303 260 37 28% 209 104% 125 90 00 37 25 18. 12 7 0 2 1 —
Data cutoff: August 8, 2023; FP: Api 7, 2020; LPI: November 9, 2022. Median survival folow-up: 172 mo. OS at 12 and 18 mo was estimated using Kaplan-Meier
method. *Calculated using strafed Cox proporional hazards model. HR <1 favors tho EV + pombokzumab arm.
1. Powis T et al N Engl J Med 2024;300:875-888. 2. ps. www da.govidrugsresources nformation-approved-drugslda-approves-enfortumab-vedotin-jv=
Pembrolzumab-ocaly.advancod-ormetastai-uroihelalcancer.
FDA Full Approval
for 1L Treatment
a of mUC?
% 2 2 8 1 4 4
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Enfortumab Vedotin Plus Pembrolizumab1
HR
- (5% cy Two-Sided P mOS (95% Cl), mo
90
80
N Ever
EV+P
442 133(80.1)
Chemo 444 226(509)
0.47
(0.38-0.
31.5 (25.
IR)
16.1 (139-183)
<.00001
70
Risk of death was reduced by
zx ® 53% in patients who received
5 50 EV + pembrolizumab
o 40
30
20
10
+ +
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32
reer Time, mo
EV+P 442 428 400 304 376 301 270 222 182 141 108 67
Chemo 444 423 303 260 37 28% 209 104% 125 90 00 37 25 18. 12 7 0 2 1 —
Data cutoff: August 8, 2023; FP: Api 7, 2020; LPI: November 9, 2022. Median survival folow-up: 172 mo. OS at 12 and 18 mo was estimated using Kaplan-Meier
method. *Calculated using strafed Cox proporional hazards model. HR <1 favors tho EV + pombokzumab arm.
1. Powis T et al N Engl J Med 2024;300:875-888. 2. ps. www da.govidrugsresources nformation-approved-drugslda-approves-enfortumab-vedotin-jv=
Pembrolzumab-ocaly.advancod-ormetastai-uroihelalcancer.
FDA Full Approval
for 1L Treatment
a of mUC?
% 2 2 8 1 4 4
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Improved PFS With
Enfortumab Vedotin Plus Pembrolizumab1
100
90
80
70
mPFS (95% CI)
mo
125 (10.4-16.6)
N Events(%) HR (95% Cl) Two-Sided P
EV+P 442 223(50.5)
0.45 (0.38-0.54)
00001
Chemo 444 307 (69.1)
g 6
g 50
Risk of
a 40 RERO
EV+pembro Es
20) death
20 reduced by 55
in patients
10
5 MS received E
pembrolizumab
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 Pere
Time, mo
No. ot Risk
EV+P A2 409 361 303 29 204 167 192 102 73 45 33 1 6 3 1 —
Chemo 44 360 27 23 14 7 56 4 30 4 8 6 S$ 3 2 1 1
Data cutoft August 8, 2023; FP: Ap 7, 2020; LPI: November 9, 2022. PFS at 12 and 18 months as estimated using Kaplan-Meier method. *Calelated using
“stated Cox proportional hazards model: HR <i favors the EV + pembrolzumab arm,
1.Powles T e al. N Engi J Med 2024:300:875-888. PeerView.com
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Enfortumab Vedotin Plus Pembrolizumab1
100
90
80
70
mPFS (95% CI)
mo
125 (10.4-16.6)
N Events(%) HR (95% Cl) Two-Sided P
EV+P 442 223(50.5)
0.45 (0.38-0.54)
00001
Chemo 444 307 (69.1)
g 6
g 50
Risk of
a 40 RERO
EV+pembro Es
20) death
20 reduced by 55
in patients
10
5 MS received E
pembrolizumab
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 Pere
Time, mo
No. ot Risk
EV+P A2 409 361 303 29 204 167 192 102 73 45 33 1 6 3 1 —
Chemo 44 360 27 23 14 7 56 4 30 4 8 6 S$ 3 2 1 1
Data cutoft August 8, 2023; FP: Ap 7, 2020; LPI: November 9, 2022. PFS at 12 and 18 months as estimated using Kaplan-Meier method. *Calelated using
“stated Cox proportional hazards model: HR <i favors the EV + pembrolzumab arm,
1.Powles T e al. N Engi J Med 2024:300:875-888. PeerView.com
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Phase 3 EV-302: Improved Overall Response’?
Significant improvement in ORR was
observed with EV + pembrolizumab
pr = = Confirmed ORR, n (%)
©
5 m cr mm (95% Cl)
© vn 2-sided P
ed 387 BOR?, n (%)
Zo
Bs CR
» PR
5 24
A SD
EV+P ‘Chemotherapy PD
MDOR (95% Cl) NR (20.2-NR) 7.0 (6.2-10.2) NE/NAS
Data cut: August 8, 2023, * BOR according to RECIST v1.1 por BICR. CR or PR was confined with repeat scans 228 air inital response,
“Patents had ether postbasolne assessment and the BOR was determined to be not evaluable per RECIST v1.1 Or no response assessment post basaine
1. Pons Total. N Engl J Med 2024;300:875-888.
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EV+P Chemotherapy
(n= 437) (n= 441)
296 (67.7) 196 (44.4)
(631-721) (39.7-492)
<.00001
127 (29.1) 55 (12.5)
169 (38.7) 141 (32.0)
82 (18.8) 149 (33.8)
38 (8.7) 60 (13.6)
21 (4.8) 36 (8.2)
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Significant improvement in ORR was
observed with EV + pembrolizumab
pr = = Confirmed ORR, n (%)
©
5 m cr mm (95% Cl)
© vn 2-sided P
ed 387 BOR?, n (%)
Zo
Bs CR
» PR
5 24
A SD
EV+P ‘Chemotherapy PD
MDOR (95% Cl) NR (20.2-NR) 7.0 (6.2-10.2) NE/NAS
Data cut: August 8, 2023, * BOR according to RECIST v1.1 por BICR. CR or PR was confined with repeat scans 228 air inital response,
“Patents had ether postbasolne assessment and the BOR was determined to be not evaluable per RECIST v1.1 Or no response assessment post basaine
1. Pons Total. N Engl J Med 2024;300:875-888.
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EV+P Chemotherapy
(n= 437) (n= 441)
296 (67.7) 196 (44.4)
(631-721) (39.7-492)
<.00001
127 (29.1) 55 (12.5)
169 (38.7) 141 (32.0)
82 (18.8) 149 (33.8)
38 (8.7) 60 (13.6)
21 (4.8) 36 (8.2)
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Phase 3 EV-302: TRAEs'?
EV +P (n= 440) Chemo (n = 433)
overat ]970 958
Peripheral Sensory Neuropathy + TRAES leading to death (per
Prurkus investigator):
- EV+P:4 (0.9%)
Alopecia
com > Asthenia
Maculopapular Rash $ Diavhea
Fatigue > Immune-mediated lung disease
Diarrhea > Multiple organ dysfunction
Decreased Appetite syndrome
— Chemotherapy: 4 (0.9%)
NoLa > Febrile neutropenia
Anemia > Myocardial infarction
Noutropenia | eve M M 54148 us > Neutropenic sepsis
Thrombocytopenia | ©7229) > as 342 > Sepsis
100 90 80 70 60 50 40 30 20 10 O 10 20 30 40 50 60 70 80 90 100
Incidence, %
Data cto: August 8, 2023, TRAES shown in fue are any grade by preferred term in 220% of patients for any grade in eher am. mn
4. Ponies Tot al ESMO 2023, Abstract LBAS. PeerView.com
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EV +P (n= 440) Chemo (n = 433)
overat ]970 958
Peripheral Sensory Neuropathy + TRAES leading to death (per
Prurkus investigator):
- EV+P:4 (0.9%)
Alopecia
com > Asthenia
Maculopapular Rash $ Diavhea
Fatigue > Immune-mediated lung disease
Diarrhea > Multiple organ dysfunction
Decreased Appetite syndrome
— Chemotherapy: 4 (0.9%)
NoLa > Febrile neutropenia
Anemia > Myocardial infarction
Noutropenia | eve M M 54148 us > Neutropenic sepsis
Thrombocytopenia | ©7229) > as 342 > Sepsis
100 90 80 70 60 50 40 30 20 10 O 10 20 30 40 50 60 70 80 90 100
Incidence, %
Data cto: August 8, 2023, TRAES shown in fue are any grade by preferred term in 220% of patients for any grade in eher am. mn
4. Ponies Tot al ESMO 2023, Abstract LBAS. PeerView.com
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Onset, Improvement, and Resolution for TRAEs of Special
Interest for Enfortumab Vedotin!
+ The majority of the EV AEs of special interest improved or resolved
Total No. of Events* With Events* With— o> Median Time To
: Y Improvement, Resolution nesto
» ion
Events," N I™Proven u First Event, |Mprovement, |Resolution,‘ mo
imolpanae) mo (Range) (Range)
Skin reaction 65 2 (3.1) 58 (89.2) 0.7 (0.1-15.7) 0.7 (0.2-1.2) 1.2 (0.1-27.1)
Peripheral neuropathy 43 20(46.5) 10233) 24(07-125) 66(03274) 7.2(3.5-19.1)
Hyperglycem 7 114.3 6 (85.7 0,5 (0 0.5 (0.5-0 1.6 (0.5-19.7)
+ Severe skin reactions were the most common TEAE of special interest for pembrolizumab
Dose Escalation + Cohort A
(N= 45)
Any Grade* Grade 23
n.(%) n (%)
Severe skin reactions 11 (24.4) 10 (22.2)
Rash maculo-popular 5 (11.1) 5 (11.1)
Dermatitis bullous 4(89) 2.4.4)
Pneumonitis 4(8.9) 4 (2.2) re reported with a higher
Colitis 3(67) 1(22) incidence in this st
Hypothyroidism 3(67) 0
"Patents could have had more than ono event > Improvement dened a atleast one grade improvement ram the wort grado athe as assessment
“ Resolutondetined ana rum fo bassine grade r betr ath an assessment or ocovered outcome. en
1. Gupta S etal. J Cn Oncol 2023:1(supp 16):4805, PeerView.com
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Interest for Enfortumab Vedotin!
+ The majority of the EV AEs of special interest improved or resolved
Total No. of Events* With Events* With— o> Median Time To
: Y Improvement, Resolution nesto
» ion
Events," N I™Proven u First Event, |Mprovement, |Resolution,‘ mo
imolpanae) mo (Range) (Range)
Skin reaction 65 2 (3.1) 58 (89.2) 0.7 (0.1-15.7) 0.7 (0.2-1.2) 1.2 (0.1-27.1)
Peripheral neuropathy 43 20(46.5) 10233) 24(07-125) 66(03274) 7.2(3.5-19.1)
Hyperglycem 7 114.3 6 (85.7 0,5 (0 0.5 (0.5-0 1.6 (0.5-19.7)
+ Severe skin reactions were the most common TEAE of special interest for pembrolizumab
Dose Escalation + Cohort A
(N= 45)
Any Grade* Grade 23
n.(%) n (%)
Severe skin reactions 11 (24.4) 10 (22.2)
Rash maculo-popular 5 (11.1) 5 (11.1)
Dermatitis bullous 4(89) 2.4.4)
Pneumonitis 4(8.9) 4 (2.2) re reported with a higher
Colitis 3(67) 1(22) incidence in this st
Hypothyroidism 3(67) 0
"Patents could have had more than ono event > Improvement dened a atleast one grade improvement ram the wort grado athe as assessment
“ Resolutondetined ana rum fo bassine grade r betr ath an assessment or ocovered outcome. en
1. Gupta S etal. J Cn Oncol 2023:1(supp 16):4805, PeerView.com
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Tactics for Safety Management:
Enfortumab Vedotin13
Skin reactions Consider topical corticosteroids and antihistamines as clinically indicated
(boxed warning) Withhold EV and refer for specialized care for suspected SJS or TEN or for severe (grade 3) skin reactions
Monitor for new or worsening PN and consider dose interruption or dose reduction when PN occurs
Permanently discontinue EV in patients who develop grade >3 PN
Peripheral neuropathy
Monitor for blurred vision and other ocular symptoms
Ocular disorders Consider prophylactic artificial tears for dry eyes and ophthalmic topical steroids after ophthalmic exam
Consider dose interruption or reduction if symptoms persist
May occur regardless of baseline glucose control
Hyperglycemia Closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia
If blood glucose is elevated (>250 mg/dL), withhold EV
Monitor for signs and symptoms in:
infiltrates on radiologic exams)
Evaluate and exclude infectious, neoplastic, and other causes for signs and symptoms through appropriate
investigations
Withhold EV for patients who develop persistent or recurrent grade 2 pneumonitis and consider dose
reduction; permanently discontinue EV in patients with grade 3 or 4 pneumonitis,
tive of pneumonitis (eg, hypoxia, cough, dyspne
terstitial
Pneumonitis
1. Padcev (enforumab vedotin) Prescribing Information. Mis www accessdata fd govidugsatiéa_docstabol 2023761 1375024802501 pat ñ
2. Pace À Gin J Oncol Nurs. 2021:25.E1.£9. 3, Lacouture ME ot al. Oncologs 202227 6223-0232. PeerView.com
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Enfortumab Vedotin13
Skin reactions Consider topical corticosteroids and antihistamines as clinically indicated
(boxed warning) Withhold EV and refer for specialized care for suspected SJS or TEN or for severe (grade 3) skin reactions
Monitor for new or worsening PN and consider dose interruption or dose reduction when PN occurs
Permanently discontinue EV in patients who develop grade >3 PN
Peripheral neuropathy
Monitor for blurred vision and other ocular symptoms
Ocular disorders Consider prophylactic artificial tears for dry eyes and ophthalmic topical steroids after ophthalmic exam
Consider dose interruption or reduction if symptoms persist
May occur regardless of baseline glucose control
Hyperglycemia Closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia
If blood glucose is elevated (>250 mg/dL), withhold EV
Monitor for signs and symptoms in:
infiltrates on radiologic exams)
Evaluate and exclude infectious, neoplastic, and other causes for signs and symptoms through appropriate
investigations
Withhold EV for patients who develop persistent or recurrent grade 2 pneumonitis and consider dose
reduction; permanently discontinue EV in patients with grade 3 or 4 pneumonitis,
tive of pneumonitis (eg, hypoxia, cough, dyspne
terstitial
Pneumonitis
1. Padcev (enforumab vedotin) Prescribing Information. Mis www accessdata fd govidugsatiéa_docstabol 2023761 1375024802501 pat ñ
2. Pace À Gin J Oncol Nurs. 2021:25.E1.£9. 3, Lacouture ME ot al. Oncologs 202227 6223-0232. PeerView.com
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Take-Home Points
+ EV as monotherapy is standard agent for refractory mUC
EV-pembrolizumab now standard combination for 1L mUC
EV is essentially a targeted chemotherapy
— Most patients will develop peripheral neuropathy
— Early dose reduction and dose delays will help mitigate
and prevent severe side effects
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+ EV as monotherapy is standard agent for refractory mUC
EV-pembrolizumab now standard combination for 1L mUC
EV is essentially a targeted chemotherapy
— Most patients will develop peripheral neuropathy
— Early dose reduction and dose delays will help mitigate
and prevent severe side effects
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Catherine’s Case: A 65-Year-Old a
Patient With Metastatic Urothelial Carcinoma
) Patient Case
A 65-year-old patient presented with
hematuria due to bladder mass
Urine cytology and TURBT: urothelial
carcinoma
CT CAP: several retroperitoneal and pelvic
lymph nodes
Clinical workup revealed
— CrCl 60 mL/min
- ECOG PS 1
— HTN, mild anemia
— No neuropathy, hearing loss or CHF
— No autoimmune disease, not on steroids
— No FGFR3 genomic alterations on NGS
— HER2 protein IHC negative
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For Panel Discussion
In developing a treatment plan for this
patient, what important factors should be
considered?
Would 1L EV + pembrolizumab be
appropriate for Catherine?
How do you educate her on expectations for
dosing/scheduling/AEs?
How would you advise her if she experiences
skin rash after starting treatment?
Do you recommend glucose monitoring?
Which team members are involved in her
education & management?
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Patient With Metastatic Urothelial Carcinoma
) Patient Case
A 65-year-old patient presented with
hematuria due to bladder mass
Urine cytology and TURBT: urothelial
carcinoma
CT CAP: several retroperitoneal and pelvic
lymph nodes
Clinical workup revealed
— CrCl 60 mL/min
- ECOG PS 1
— HTN, mild anemia
— No neuropathy, hearing loss or CHF
— No autoimmune disease, not on steroids
— No FGFR3 genomic alterations on NGS
— HER2 protein IHC negative
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For Panel Discussion
In developing a treatment plan for this
patient, what important factors should be
considered?
Would 1L EV + pembrolizumab be
appropriate for Catherine?
How do you educate her on expectations for
dosing/scheduling/AEs?
How would you advise her if she experiences
skin rash after starting treatment?
Do you recommend glucose monitoring?
Which team members are involved in her
education & management?
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Targeting Trop-2
ADC Therapy for Metastatic
Urothelial Cancer
Petros Grivas, MD, PhD
Professor
Division of Hematology and Oncology, Department of Medicine
Clinical Director, Genitourinary Cancers Program
University of Washington School of Medicine
Professor, Clinical Research Division
Fred Hutchinson Cancer Center
Seattle, Washington
Copyright © 2000-2024, Peerview
ADC Therapy for Metastatic
Urothelial Cancer
Petros Grivas, MD, PhD
Professor
Division of Hematology and Oncology, Department of Medicine
Clinical Director, Genitourinary Cancers Program
University of Washington School of Medicine
Professor, Clinical Research Division
Fred Hutchinson Cancer Center
Seattle, Washington
Copyright © 2000-2024, Peerview
Trop-2 mRNA Expression Across Cancer Types!
‘Study of Origin
tion Status
"= Tant WS) © ae US)
Em Seemann rc
or op
Deep cn © Mare Cana ts
Trop-2 mRNA:
Highly expressed
across multiple types
of cancer in the TCGA
database, with high
expression in
urothelial carcinoma
TROP2 Expression Log (ASE)
1. Ghou Jet al. Eur Urol Onco. 2022;82586-9311(21)002157 PeerView.com
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‘Study of Origin
tion Status
"= Tant WS) © ae US)
Em Seemann rc
or op
Deep cn © Mare Cana ts
Trop-2 mRNA:
Highly expressed
across multiple types
of cancer in the TCGA
database, with high
expression in
urothelial carcinoma
TROP2 Expression Log (ASE)
1. Ghou Jet al. Eur Urol Onco. 2022;82586-9311(21)002157 PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
Trop-2 Is Highly Expressed Across
Molecular Subtypes of UC‘?
Lump
+ Trop-2 protein
Highly expressed across
basal, luminal, and stroma:
rich subtypes, but depleted in
the neuroendocrine subtype
Cells resistant to enfortumab
vedotin, a Nectin-4—targeting
ADC, remain sensitive to
sacituzumab govitecan
TROP? protein expression in molecular subtypes of bladder cancer (A-F). Representative immunohistochemisty staining for TROP2 in the
Ba/Sq (A), LumNS (8), LumP (C), LumU (0), NE-ike (E), and Stroma-rich (F) bladder cancer subtypes using a bladder cancer tissue
microarray (TMA). The subtypes were previously determined as described in Seiler et al, 2017. Scale bar denotes 100 um
1. Ghou J eta Eur Url Oncol. 2022:52588-9911(21)00215-7. 2, Soler Rot al. Eur Ur 2017:72:544.554.
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Copyright © 2000-2024, PeerView
Molecular Subtypes of UC‘?
Lump
+ Trop-2 protein
Highly expressed across
basal, luminal, and stroma:
rich subtypes, but depleted in
the neuroendocrine subtype
Cells resistant to enfortumab
vedotin, a Nectin-4—targeting
ADC, remain sensitive to
sacituzumab govitecan
TROP? protein expression in molecular subtypes of bladder cancer (A-F). Representative immunohistochemisty staining for TROP2 in the
Ba/Sq (A), LumNS (8), LumP (C), LumU (0), NE-ike (E), and Stroma-rich (F) bladder cancer subtypes using a bladder cancer tissue
microarray (TMA). The subtypes were previously determined as described in Seiler et al, 2017. Scale bar denotes 100 um
1. Ghou J eta Eur Url Oncol. 2022:52588-9911(21)00215-7. 2, Soler Rot al. Eur Ur 2017:72:544.554.
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ADCs Targeting Trop-2!
Jatopotamab Deruxt
Sacituzumab Govitecan
EEN
Hydrotysable ‘Totrapeptide-based
pH-sensitive linker ‘leavable tinker
for Xa
Download the
Practice Aid to
= learn more
es about ADC
‘0x more potent
than N38),
‘Signal peptide
ptm \
Pa Q Son
epidemal Humanized
ant-TROPZ 1961 MAD grow factor. ‘ant-TROP2 1901 mAD
Feo repeat
oman TROP
Micron
repr
1. Parsi eta. Cancer Treat Rov.2023:118:102572. PeerView.com
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Jatopotamab Deruxt
Sacituzumab Govitecan
EEN
Hydrotysable ‘Totrapeptide-based
pH-sensitive linker ‘leavable tinker
for Xa
Download the
Practice Aid to
= learn more
es about ADC
‘0x more potent
than N38),
‘Signal peptide
ptm \
Pa Q Son
epidemal Humanized
ant-TROPZ 1961 MAD grow factor. ‘ant-TROP2 1901 mAD
Feo repeat
oman TROP
Micron
repr
1. Parsi eta. Cancer Treat Rov.2023:118:102572. PeerView.com
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Sacituzumab Govitecan Is a First-in-Class
Trop-2-Directed ADC
Humanized anti-Trop-2
AIN | Trop-2 is an epithelial cell surface antigen highly
pithelial antigen expressed in many solid tumors including invasive
A | reset cancer!
inct from other ADCs:2*
SN-38
cad + High drug-to-antibody ratio (7.6:1)
potent than e.
Internalization and enzymatic cleavage by tumor cell not
required for SN-38 (active metabolite of irinotecan)
liberation from antibody
FDA-approved for the followin
+ Treatment of patients with metastatic triple-negative
Hydrolyzable breast cancer (TNBC) who received 22 prior
linker for SN-38 chemotherapies (21 in metastatic setting)”
ign drug: + Treatment of patients with locally advanced or metastatic
ES UC who previously received platinum-containing
chemotherapy and PD-1/L1 inhibitor”=
This lndcation is based on FDA acceloratod approval
4. Avolini © ota. Oncotarget. 2017:8:58642-58053 2. Goldenberg OM et al. Expert Opin Bol Ter. 2020;20:871-885. 3. Nagayama A et al. Thor Adv Med Oncol
2020.12:1-12.4. Carlo TM etal. Bioconjugate Chom. 2018:28:819-831. 5. Goldenberg DM etal. Oncotarge. 2015.6:22496-224512.
6. Govindan SV et al. Mol Cancer Ther. 2013;12:908-978.7. Trodely (sactuzumab govtecan-hziy) Preserbing information, peervie
tos in acesedata fa govirugsatisa_doestabel 2023/7641 15s0350 pa. eerView.com
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Trop-2-Directed ADC
Humanized anti-Trop-2
AIN | Trop-2 is an epithelial cell surface antigen highly
pithelial antigen expressed in many solid tumors including invasive
A | reset cancer!
inct from other ADCs:2*
SN-38
cad + High drug-to-antibody ratio (7.6:1)
potent than e.
Internalization and enzymatic cleavage by tumor cell not
required for SN-38 (active metabolite of irinotecan)
liberation from antibody
FDA-approved for the followin
+ Treatment of patients with metastatic triple-negative
Hydrolyzable breast cancer (TNBC) who received 22 prior
linker for SN-38 chemotherapies (21 in metastatic setting)”
ign drug: + Treatment of patients with locally advanced or metastatic
ES UC who previously received platinum-containing
chemotherapy and PD-1/L1 inhibitor”=
This lndcation is based on FDA acceloratod approval
4. Avolini © ota. Oncotarget. 2017:8:58642-58053 2. Goldenberg OM et al. Expert Opin Bol Ter. 2020;20:871-885. 3. Nagayama A et al. Thor Adv Med Oncol
2020.12:1-12.4. Carlo TM etal. Bioconjugate Chom. 2018:28:819-831. 5. Goldenberg DM etal. Oncotarge. 2015.6:22496-224512.
6. Govindan SV et al. Mol Cancer Ther. 2013;12:908-978.7. Trodely (sactuzumab govtecan-hziy) Preserbing information, peervie
tos in acesedata fa govirugsatisa_doestabel 2023/7641 15s0350 pa. eerView.com
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TROPHY-U-01: Sacituzumab Govitecan in Pretreated
Metastatic Urothelial Carcinoma!
Cohort 1 (113 patients)
Patients with mUC who progressed
after prior PT- and CPI-based ther
Cohort 2 (38 patients)
Patient with mUC who progressed
in cisplatin-ineligible pt
Cohort 3 (41 patients)
atents with mUC who progressed
‘after prior PT-based chemotherapy
SG 10 mg/kg
Day 1 and day 8, every 21 days
SG 10 mg/kg
Day 1 and day 8, every 21 days
SG 10 mgikg
Day 1 and day 8, every 21 days +
embro 200 mg day 1 every 21 days
Induction: Cis + SG (6 cycles)
Maintenance: (1) SG + avelumab
(2) SG + zimberelimab (zim)
Arms
(1) 56 + zim; (2) an
lumab; (3) zim
Arms,
(1) SG: (2) SG + zim; (3) SG + zim + dom;
(4) carbo + gem + avelumab maintenance
7. Powe T etal. J Gin Oncol 2023:41.6. suppl. TPSS98, 8. Duran | tal J Cin Oncol 2023:41 6. suppl TPSS9Z.
2021
Accelerated FDA
approval
for patients with locally
advanced or mUC who
previously received
platinum-containing
chemotherapy and
PD-4/PD-L1 inhibitor
Cohorts 1-5 are closed for enrollment
1. hps:/einiatialsgovlet2showNCTO3647973. 2. Lovet Y et al. Ann Oncol. 2020;31(suppl 81142-81215. 3, Petylak DP et al. J in Oncol, 2024 accepted.
4. Grvas P ot al. J Cin Oncol 2024 42:1415-1425, 5. Loto Y etal. Ann Oncol 2024.35 392-401. 6. Ramamurthy Geta. J Cin Oncol 2023:41.16_ suppl. TPS4611,
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Metastatic Urothelial Carcinoma!
Cohort 1 (113 patients)
Patients with mUC who progressed
after prior PT- and CPI-based ther
Cohort 2 (38 patients)
Patient with mUC who progressed
in cisplatin-ineligible pt
Cohort 3 (41 patients)
atents with mUC who progressed
‘after prior PT-based chemotherapy
SG 10 mg/kg
Day 1 and day 8, every 21 days
SG 10 mg/kg
Day 1 and day 8, every 21 days
SG 10 mgikg
Day 1 and day 8, every 21 days +
embro 200 mg day 1 every 21 days
Induction: Cis + SG (6 cycles)
Maintenance: (1) SG + avelumab
(2) SG + zimberelimab (zim)
Arms
(1) 56 + zim; (2) an
lumab; (3) zim
Arms,
(1) SG: (2) SG + zim; (3) SG + zim + dom;
(4) carbo + gem + avelumab maintenance
7. Powe T etal. J Gin Oncol 2023:41.6. suppl. TPSS98, 8. Duran | tal J Cin Oncol 2023:41 6. suppl TPSS9Z.
2021
Accelerated FDA
approval
for patients with locally
advanced or mUC who
previously received
platinum-containing
chemotherapy and
PD-4/PD-L1 inhibitor
Cohorts 1-5 are closed for enrollment
1. hps:/einiatialsgovlet2showNCTO3647973. 2. Lovet Y et al. Ann Oncol. 2020;31(suppl 81142-81215. 3, Petylak DP et al. J in Oncol, 2024 accepted.
4. Grvas P ot al. J Cin Oncol 2024 42:1415-1425, 5. Loto Y etal. Ann Oncol 2024.35 392-401. 6. Ramamurthy Geta. J Cin Oncol 2023:41.16_ suppl. TPS4611,
PeerView.com
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TROPHY-U-01 Cohort 1: Sacituzumab Govitecan in
Platinum- and Immune Checkpoint Inhibitor-Refractory Setting!
Best overall response EN Cohort 4
)
u ORR, % 28
mDOR, mo 82
mPFS, mo 54
mOS, mo 10.9
Best Percent Change From Baseline
100 Patient
1. LoriotY ot al Ann Oncol 2024; 35.362. PeerView.com
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Platinum- and Immune Checkpoint Inhibitor-Refractory Setting!
Best overall response EN Cohort 4
)
u ORR, % 28
mDOR, mo 82
mPFS, mo 54
mOS, mo 10.9
Best Percent Change From Baseline
100 Patient
1. LoriotY ot al Ann Oncol 2024; 35.362. PeerView.com
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TROPHY-U-01 Cohort 1: Sacituzumab Govitecan in
Platinum- and Immune Checkpoint Inhibitor-Refractory Setting!
Percant Change From Basel
in Tage Lions
Discontinued without event
> Ongoing response
Ont of response
MM PO or death
Time, mo
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1. Loi Y otal. Ann Oncol 2024; 35.362.
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Platinum- and Immune Checkpoint Inhibitor-Refractory Setting!
Percant Change From Basel
in Tage Lions
Discontinued without event
> Ongoing response
Ont of response
MM PO or death
Time, mo
PeerView.com
1. Loi Y otal. Ann Oncol 2024; 35.362.
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Phase 3 TROPiCS-04'
Key Eligibility Criteria
Locally advanced
unresectable or mU itisumab aovite Continue
Sacituzumab govitecan reatmentuntil Primary Endpoint
Up + tract 10 mg/kg loss ofcinical = pe
tumors f o benefit or
Peers unacceptable Secondary Endpoints
Mixed histolo as
allowed if urothelial + PFS by PI
histology predominant assessment using
P nen taxel @ 75 mg/m RECIST 1.1
platinum-based and OR + ORR, DOR, and
anti-PD-1/PD-L1 itaxel @ 175 mg/m CBR by PI
therapy OR assessment using
GA Vinflunine @ 320 mg/m RECIST 1.1
n Dt of 21-day cycle + EORTC QLQ C30
Platinum in neo/ad) score and EuroQOL
setting if progression EQ-5D-5L GOL
within 12 months and score
subsequent CPI
1. Grivas eta. J Gin Oncol2021:39. PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
Key Eligibility Criteria
Locally advanced
unresectable or mU itisumab aovite Continue
Sacituzumab govitecan reatmentuntil Primary Endpoint
Up + tract 10 mg/kg loss ofcinical = pe
tumors f o benefit or
Peers unacceptable Secondary Endpoints
Mixed histolo as
allowed if urothelial + PFS by PI
histology predominant assessment using
P nen taxel @ 75 mg/m RECIST 1.1
platinum-based and OR + ORR, DOR, and
anti-PD-1/PD-L1 itaxel @ 175 mg/m CBR by PI
therapy OR assessment using
GA Vinflunine @ 320 mg/m RECIST 1.1
n Dt of 21-day cycle + EORTC QLQ C30
Platinum in neo/ad) score and EuroQOL
setting if progression EQ-5D-5L GOL
within 12 months and score
subsequent CPI
1. Grivas eta. J Gin Oncol2021:39. PeerView.com
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TROPHY-U-01 Cohort 2: Sacituzumab Govitecan for
Cisplatin-Ineligible Patients’
Best Percent Change From Baseline
Cohort 2
(N= 38)
‘ORR, %. 32
mDOR, mo 72
mPFS, mo 56
mOS, mo 135
Best overall BEM PR (n= 12)
Less) SD(n=19)
mm PO(n=3)
1 Discontinued without event
ongoing response
MM onset of response
PO or death
Modan olow-up: 93 months
1. Petyiak DP et al. ASCO GU 2023. Abstract 520.
PeerView.com/MBD827
[(EREFTFETEEE.
Time, mo
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Cisplatin-Ineligible Patients’
Best Percent Change From Baseline
Cohort 2
(N= 38)
‘ORR, %. 32
mDOR, mo 72
mPFS, mo 56
mOS, mo 135
Best overall BEM PR (n= 12)
Less) SD(n=19)
mm PO(n=3)
1 Discontinued without event
ongoing response
MM onset of response
PO or death
Modan olow-up: 93 months
1. Petyiak DP et al. ASCO GU 2023. Abstract 520.
PeerView.com/MBD827
[(EREFTFETEEE.
Time, mo
PeerView.com
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TROPHY-U-01 Cohort 3: CPI-Naive Patients!
muc
Treatment continued
+ Platinum-refractory SG + pembrolizumab until progression or
unmanageable toxicity
+ CPl-naive
Primary endpoint: ORR (central review)
Secondary endpoints included: PFS, CBR, DOR, safety
Median follow-up: 14.8 mo
1. Gras Petal, J Cin Oncol. 2024:42:1415-1425, PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
muc
Treatment continued
+ Platinum-refractory SG + pembrolizumab until progression or
unmanageable toxicity
+ CPl-naive
Primary endpoint: ORR (central review)
Secondary endpoints included: PFS, CBR, DOR, safety
Median follow-up: 14.8 mo
1. Gras Petal, J Cin Oncol. 2024:42:1415-1425, PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
TROPHY-U-01 Trial Cohort 3: Primary Endpoint Was Met!
Endpoi
ORR, %
CR, %
PR, %
mDOR, mo
mPFS, mo
mOS, mo
1. Givas Pa J Cin Oncol 202442:1415-1425
PeerView.com/MBD827
Cohort 3
(N = 41)
41
20
21
11.1
5.3
12.7
Percent Change From Baseline
‘Target Lesions
‘Best Percent Change From Baseline
Responder
m NE (9=3) Patient
PeerView.com
Copyright © 2000-2024, PeerView
Endpoi
ORR, %
CR, %
PR, %
mDOR, mo
mPFS, mo
mOS, mo
1. Givas Pa J Cin Oncol 202442:1415-1425
PeerView.com/MBD827
Cohort 3
(N = 41)
41
20
21
11.1
5.3
12.7
Percent Change From Baseline
‘Target Lesions
‘Best Percent Change From Baseline
Responder
m NE (9=3) Patient
PeerView.com
Copyright © 2000-2024, PeerView
EA8231: Proposed Phase 3 Trial?
Key Eligibility Criteria
Metastatic or LA
unresectable
ECOG PS 0-2
Anti-PD-L1 therapy
required; prior
platinum-bases
Tx & EN
ed
mic
therapy for advanced
UC setting in FGFR2
(unknown (s
of therapy for
FGFR2/3
mutation/fusion)
+ Side courtesy of Dr Potros Gras
PeerView.com/MBD827
chemo
umab Primary Endpoint
os
Secondary Endpoints
+ PFS
+ ORR
+ QOL/PRO
+ Safety/toxicity
Stratification Factors
+ Bellmunt score (0-1 vs 2-3)
+ Prior exposure to enfortumab vedotin .
+ Prior exposure to platinum (cisplatin or carboplatin)- .
based chemotherapy .
+ Primary vs acquired resistance to anti PD-L1 therapy
Primary resistance: PD within 6 mo from starting anti PD-L1
Acquired resistance: PD after 6 mo from starting anti PD-L1
Correlative Biomarkers
NGS: DNA/RNA tumor
Trop-2 IHC
PD-L1 IHC
TMB, MSI status
ctDNA in blood/urine
PeerView.com
Copyright © 2000-2024, PeerView
Key Eligibility Criteria
Metastatic or LA
unresectable
ECOG PS 0-2
Anti-PD-L1 therapy
required; prior
platinum-bases
Tx & EN
ed
mic
therapy for advanced
UC setting in FGFR2
(unknown (s
of therapy for
FGFR2/3
mutation/fusion)
+ Side courtesy of Dr Potros Gras
PeerView.com/MBD827
chemo
umab Primary Endpoint
os
Secondary Endpoints
+ PFS
+ ORR
+ QOL/PRO
+ Safety/toxicity
Stratification Factors
+ Bellmunt score (0-1 vs 2-3)
+ Prior exposure to enfortumab vedotin .
+ Prior exposure to platinum (cisplatin or carboplatin)- .
based chemotherapy .
+ Primary vs acquired resistance to anti PD-L1 therapy
Primary resistance: PD within 6 mo from starting anti PD-L1
Acquired resistance: PD after 6 mo from starting anti PD-L1
Correlative Biomarkers
NGS: DNA/RNA tumor
Trop-2 IHC
PD-L1 IHC
TMB, MSI status
ctDNA in blood/urine
PeerView.com
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What About Earlier Disease?
Sacituzumab Govitecan in MIBC
Key Protocol Amendments?
Dose reduction of $
mg/kg from C1D1
Introduction of G-C:
primary prophylax
Exclusion of patients with
factors for febrile neutropenia as
indicated by À uidelines
Open al ang am, phase 1 a
+ pu econo NOTES 7.2. Cola À PeerView.com
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Sacituzumab Govitecan in MIBC
Key Protocol Amendments?
Dose reduction of $
mg/kg from C1D1
Introduction of G-C:
primary prophylax
Exclusion of patients with
factors for febrile neutropenia as
indicated by À uidelines
Open al ang am, phase 1 a
+ pu econo NOTES 7.2. Cola À PeerView.com
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Combining ADCs?
Double Antibody-Drug (DAD) conjugate
phase | trial of SG + EV as 22L therapy for mUC*
E mes —}
SG EV
8 mg/kg 1 mglkg with encouraging efficacy in treatment resistant mUC as
OEI evidenced by an ORR of 70% in 23 evaluable patients
Given cumulative toxicities and efficacy across dose
levels, the recommended phase 2 dose was
SG 7.5 mg/kg and EV 1.25 mg/kg D1,8 of 21-day cycle
SG + EV demonstrated favorable safety at DL3 along
Smorkg 1 mg/kg
Both drugs given D1,8 of a 21 day cycle
20/23 with any degree of shrinkage in target lesions
As EV + P is now a standard of care for 1L mUC, the
DAD trial was amended to include 2 cohorts of
LE distinct patient populations?:
sé - SG+EV(DAD)
HE - SG+EV+P (DAD-IO)
5
3 =
Patients
1. McGregor BA et al. ESMO 2023 Abstract 23800. 2. McGregor BA et al. ASCO 2024 TPS4618. PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
Double Antibody-Drug (DAD) conjugate
phase | trial of SG + EV as 22L therapy for mUC*
E mes —}
SG EV
8 mg/kg 1 mglkg with encouraging efficacy in treatment resistant mUC as
OEI evidenced by an ORR of 70% in 23 evaluable patients
Given cumulative toxicities and efficacy across dose
levels, the recommended phase 2 dose was
SG 7.5 mg/kg and EV 1.25 mg/kg D1,8 of 21-day cycle
SG + EV demonstrated favorable safety at DL3 along
Smorkg 1 mg/kg
Both drugs given D1,8 of a 21 day cycle
20/23 with any degree of shrinkage in target lesions
As EV + P is now a standard of care for 1L mUC, the
DAD trial was amended to include 2 cohorts of
LE distinct patient populations?:
sé - SG+EV(DAD)
HE - SG+EV+P (DAD-IO)
5
3 =
Patients
1. McGregor BA et al. ESMO 2023 Abstract 23800. 2. McGregor BA et al. ASCO 2024 TPS4618. PeerView.com
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Datopotamab Deruxtecan: TROPION-PanTumor011
Key Eligibility Criteria (Urothelial Cancer Cohort)
Treatment
arg Primary endpoints: Safety and tolerability
Secondary endpoints: ORR, DOR, DCR,
6 mg/kg QW PFS (evaluated via BICR per RECIST 1.1)
ior treatment with D es
Total planned patient number = 40
Tumor Response by BICR
3 valuable Patients With 2 Post-
cee) Patients (N = 26) Baseline Scans (N = 22)
‘ORR (confirmed) 227)
165-394) 178454)
163) 1(45)
PR 4(154) 4(182)
Non-CRinon-PD 108) 145)
so 15677 11600)
pcr 21608) 17073)
(65% cl) (606-934) (646922)
po 305) 31138)
NE 2077 20
1. Lisberg A et al. ASCO-GU 2024. Abstract 603. PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
Key Eligibility Criteria (Urothelial Cancer Cohort)
Treatment
arg Primary endpoints: Safety and tolerability
Secondary endpoints: ORR, DOR, DCR,
6 mg/kg QW PFS (evaluated via BICR per RECIST 1.1)
ior treatment with D es
Total planned patient number = 40
Tumor Response by BICR
3 valuable Patients With 2 Post-
cee) Patients (N = 26) Baseline Scans (N = 22)
‘ORR (confirmed) 227)
165-394) 178454)
163) 1(45)
PR 4(154) 4(182)
Non-CRinon-PD 108) 145)
so 15677 11600)
pcr 21608) 17073)
(65% cl) (606-934) (646922)
po 305) 31138)
NE 2077 20
1. Lisberg A et al. ASCO-GU 2024. Abstract 603. PeerView.com
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Datopotamab Deruxtecan: TROPION-PanTumor011:2
100 I Prior enfortumab vedotin + prior chemotherapy
e IM Prior enfortumab vedotin + no prior chemotherapy
© No prior enfortumab vedotin + prior chemotherapy
8
o
2
o
0
o
-100
Patients with tumor burden reduction:
82% (18/22)
Change in Sum of Diameters
From Baseline, %
1. Lisberg A et al ASCO-GU 2024. Abstract 603. 2. tpsIciicalils govistudyINCTOS46027S 3, htpsi/cknicatals. govistodyINCTOS489211, PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
100 I Prior enfortumab vedotin + prior chemotherapy
e IM Prior enfortumab vedotin + no prior chemotherapy
© No prior enfortumab vedotin + prior chemotherapy
8
o
2
o
0
o
-100
Patients with tumor burden reduction:
82% (18/22)
Change in Sum of Diameters
From Baseline, %
1. Lisberg A et al ASCO-GU 2024. Abstract 603. 2. tpsIciicalils govistudyINCTOS46027S 3, htpsi/cknicatals. govistodyINCTOS489211, PeerView.com
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Using Approved ADCs in the Clinic: Q
Tactics for Safety Management!
Sacituzumab Govitecan
Neutropenia
Key Grade 23 TRAES Recommend G-CSF as primary prophylaxis
From TROPHY-U-01 Cohort 1 Dose reduction/delay as needed
Neutropenia (35%) Educate & monitor patients very well; urgent care if needed
Leukopenia (18%)
Anemia (14%) Diarrhea
Educate patients very well; rule out other causes
Hydration with electrolytes, monitor labs
Anti-diarrheal medications/best supportive care
Diarrhea (10%)
Febrile neutropenia (10%)
4. Lot Y tal, Ann Oncol. 2024; 35:92. 2. Trodehy (sactuzumab govitecan¿hzy) Prescrbing Information. 7
its: /hwww accessdata.(da govidrugsatida_docs/abel2023/761 11503500 pa. PeerView.com
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Tactics for Safety Management!
Sacituzumab Govitecan
Neutropenia
Key Grade 23 TRAES Recommend G-CSF as primary prophylaxis
From TROPHY-U-01 Cohort 1 Dose reduction/delay as needed
Neutropenia (35%) Educate & monitor patients very well; urgent care if needed
Leukopenia (18%)
Anemia (14%) Diarrhea
Educate patients very well; rule out other causes
Hydration with electrolytes, monitor labs
Anti-diarrheal medications/best supportive care
Diarrhea (10%)
Febrile neutropenia (10%)
4. Lot Y tal, Ann Oncol. 2024; 35:92. 2. Trodehy (sactuzumab govitecan¿hzy) Prescrbing Information. 7
its: /hwww accessdata.(da govidrugsatida_docs/abel2023/761 11503500 pa. PeerView.com
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Download the
Practice Aid
learn more about
ADC Safety
Management
Tactics for Safety Management:
Sacituzumab Govitecan!3
5 Hypersensitivity Diarrhea and Cholinergic
Nausea/Vomiting Reactions ‘Syndrome Neutropenia
+ SG is moderately + Serious and life- + Monitor patients with + Withhold for ANC
‘emetogenic (>30% to threatening HSRs diarrhea and give fluid <1,500/mm? on day 1
90% risk of emesis) have been reported and electrolytes as or neutropenic fever
+ Premedicate with a with SG needed + Monitor blood cell
5-HT antagonist & + Premedicate with an + Administer anti-diarthea counts periodically
dexamethasone prior antipyretic, H1 & H2 meds, if not during treatment
to each infusion on blockers prior to each contraindicated, for early. Consider G-CSF for
day 1 infusion diarrhea of any severity primary prophiviaxts
o + Initiate anti-infective
not routinely used nor treatment in patients
recommended in patients with febrile
who have not previously neutropenia without
experienced diarrhea delays edlen Be)
1. ping LM ot a. Oncogis.202126:.27-834.2. Trodey (sactuzumab govtecan y Prescbing Information. ñ
https ww accessdata da govidrugsatida_docs/labeV2022/76111550231 paf. 3. Hesketh PJ eta. J Clin Oncol. 2020.38(24)2782-2797. PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, Peerview
Practice Aid
learn more about
ADC Safety
Management
Tactics for Safety Management:
Sacituzumab Govitecan!3
5 Hypersensitivity Diarrhea and Cholinergic
Nausea/Vomiting Reactions ‘Syndrome Neutropenia
+ SG is moderately + Serious and life- + Monitor patients with + Withhold for ANC
‘emetogenic (>30% to threatening HSRs diarrhea and give fluid <1,500/mm? on day 1
90% risk of emesis) have been reported and electrolytes as or neutropenic fever
+ Premedicate with a with SG needed + Monitor blood cell
5-HT antagonist & + Premedicate with an + Administer anti-diarthea counts periodically
dexamethasone prior antipyretic, H1 & H2 meds, if not during treatment
to each infusion on blockers prior to each contraindicated, for early. Consider G-CSF for
day 1 infusion diarrhea of any severity primary prophiviaxts
o + Initiate anti-infective
not routinely used nor treatment in patients
recommended in patients with febrile
who have not previously neutropenia without
experienced diarrhea delays edlen Be)
1. ping LM ot a. Oncogis.202126:.27-834.2. Trodey (sactuzumab govtecan y Prescbing Information. ñ
https ww accessdata da govidrugsatida_docs/labeV2022/76111550231 paf. 3. Hesketh PJ eta. J Clin Oncol. 2020.38(24)2782-2797. PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, Peerview
Tactics for Safety Management:
Datopotamab Deruxtecan‘?
Al-Cause TEAEs Occurring in 210% of Patients
Stomatitis
Nau
RE Oral mucositis/stomatitis
ve Gently brush teeth
Decreased appetite ently brush tee!
il f 1-¢
Daily use of steroid-containing mouthwash
orador Educate on importance of oral hygiene
Cough Bot Ocular surface events
Vomiting nn Use artificial tears as needed
Diarrhea — Avoid contact lenses
5 >
Any Grade | Grade 1 Grade 3 n | Dose Interruption | 1:
Oral mucositis/stomatitis 18(5) 12(96) 412) 26) 16
Ocular surface events sus) 30 26) o 26)
IRR 26) 10) 10 o o 16
Adjudicated drug-related ILD 16) o 16) o o 10 o
1. Lisberg A et al. ASCO-GU 2024. Abstract 603. 2. Heist RS et al. Cancer Treat Rov.2024:125:102720. PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
Datopotamab Deruxtecan‘?
Al-Cause TEAEs Occurring in 210% of Patients
Stomatitis
Nau
RE Oral mucositis/stomatitis
ve Gently brush teeth
Decreased appetite ently brush tee!
il f 1-¢
Daily use of steroid-containing mouthwash
orador Educate on importance of oral hygiene
Cough Bot Ocular surface events
Vomiting nn Use artificial tears as needed
Diarrhea — Avoid contact lenses
5 >
Any Grade | Grade 1 Grade 3 n | Dose Interruption | 1:
Oral mucositis/stomatitis 18(5) 12(96) 412) 26) 16
Ocular surface events sus) 30 26) o 26)
IRR 26) 10) 10 o o 16
Adjudicated drug-related ILD 16) o 16) o o 10 o
1. Lisberg A et al. ASCO-GU 2024. Abstract 603. 2. Heist RS et al. Cancer Treat Rov.2024:125:102720. PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
Supporting Effective Communication Among
Multidisciplinary Healthcare Teams S
Encouragement for
patients to report AES
early and not wait until
next appointment
Clear education for
patients regarding
expected AEs
Maintain connections
between clinical
departments (eg, primary
care, urology, oncology)
Training for nurses
to recognize and support
accurate triage
Established point of contact
to guide and navigate
patients between points of
care
Established subspecialty referrals
(eg, dermatology, ophthalmology,
gastroenterology, endocrinology)
PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, Peerview
Multidisciplinary Healthcare Teams S
Encouragement for
patients to report AES
early and not wait until
next appointment
Clear education for
patients regarding
expected AEs
Maintain connections
between clinical
departments (eg, primary
care, urology, oncology)
Training for nurses
to recognize and support
accurate triage
Established point of contact
to guide and navigate
patients between points of
care
Established subspecialty referrals
(eg, dermatology, ophthalmology,
gastroenterology, endocrinology)
PeerView.com
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Joseph’s Case: A 72-Year-Old
Patient With Progressing Metastatic Urothelial Carcinom
+ A 72-year-old patient presented with symptomatic
progression with fatigue and back pain
+ Previous treatment with cis/gem — switch
maintenance avelumab
‘Gilnieat workup revealed
CT CAP showed liver and bone mets
+ ECOGPS1
+ NGS of primary bladder tumor tissue showed no
FGFR3 alterations, IHC 1+ for HER2 protein
+ HbA1c 9.2% (has not seen endocrinologist)
* G2 neuropathy (impacting ADLs)
* Obese, “cirrhotic” liver appearance on CT (no
formal diagnosis of liver cirrhosis)
PeerView.com/MBD827
For Panel Discussion
In developing a treatment plan for Joseph,
what important factors should be considered
for the 2L setting?
How do you educate him on expectations for
dosing/scheduling?
What AEs does the care team need to be
mindful of?
How would you advise him if he experiences
diarrhea after starting treatment?
PeerView.com
Copyright © 2000-2024, PeerView
Patient With Progressing Metastatic Urothelial Carcinom
+ A 72-year-old patient presented with symptomatic
progression with fatigue and back pain
+ Previous treatment with cis/gem — switch
maintenance avelumab
‘Gilnieat workup revealed
CT CAP showed liver and bone mets
+ ECOGPS1
+ NGS of primary bladder tumor tissue showed no
FGFR3 alterations, IHC 1+ for HER2 protein
+ HbA1c 9.2% (has not seen endocrinologist)
* G2 neuropathy (impacting ADLs)
* Obese, “cirrhotic” liver appearance on CT (no
formal diagnosis of liver cirrhosis)
PeerView.com/MBD827
For Panel Discussion
In developing a treatment plan for Joseph,
what important factors should be considered
for the 2L setting?
How do you educate him on expectations for
dosing/scheduling?
What AEs does the care team need to be
mindful of?
How would you advise him if he experiences
diarrhea after starting treatment?
PeerView.com
Copyright © 2000-2024, PeerView
HER2-Targeted ADC Therapy
for Metastatic Urothelial Cancer
Evan Y. Yu, MD
Section Head, Medical Oncology, Clinical Research Division
Fred Hutchinson Cancer Center
Medical Director, Clinical Research Support
Fred Hutchinson Cancer Research Consortium
Professor of Medicine
Division of Hematology and Oncology, Department of Medicine
University of Washington School of Medicine
Seattle, Washington
Copyright © 2000-2024, PeerView
for Metastatic Urothelial Cancer
Evan Y. Yu, MD
Section Head, Medical Oncology, Clinical Research Division
Fred Hutchinson Cancer Center
Medical Director, Clinical Research Support
Fred Hutchinson Cancer Research Consortium
Professor of Medicine
Division of Hematology and Oncology, Department of Medicine
University of Washington School of Medicine
Seattle, Washington
Copyright © 2000-2024, PeerView
HER2: Overexpression, Amplification,
and Mutations Across Tumor Types!-3
‘Atlas Research ‘Nat Gonot. 2013:45:1113-1120. 2. AACR Project GENIE Consortum. Cancer Discov. 2017:7:818-831.
‚nr Genome Alas Network.
SEN et Nt Rey Cin Oncol 2000 1 3948,
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Colorectum |
PeerView.com
Copyright © 2000-2024, PeerView
and Mutations Across Tumor Types!-3
‘Atlas Research ‘Nat Gonot. 2013:45:1113-1120. 2. AACR Project GENIE Consortum. Cancer Discov. 2017:7:818-831.
‚nr Genome Alas Network.
SEN et Nt Rey Cin Oncol 2000 1 3948,
PeerView.com/MBD827
Colorectum |
PeerView.com
Copyright © 2000-2024, PeerView
HER2 Expression in Locally Advanced/Metastatic
Urothelial Bladder Cancer (LA/mUC)
+ HER2 IHC not typically assessed as part of standard clinical care
+ No standardized criteria for defining HER2 expression
Systemic Literature Review of reported HER2 status in LA/mUC
+ Asignificant proportion of patients with
LA/mUC have tumors with HER2
expression based on pre-defined criteria
+ HER2+ (IHC 3+ OR IHC 2+ / ISH+):
12.3% weighted avg
(6 studies, N = 971 pts)
+ HER2 low (IHC 2+/ISH- OR IHC 1+):
47.9% weighted avg
(4 studies, N = 275 pts)
Data onside courtesy of Vadim Koshkin rom: Scherrer E, ot a Front Oncol 2022:12:101 1886. PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
Urothelial Bladder Cancer (LA/mUC)
+ HER2 IHC not typically assessed as part of standard clinical care
+ No standardized criteria for defining HER2 expression
Systemic Literature Review of reported HER2 status in LA/mUC
+ Asignificant proportion of patients with
LA/mUC have tumors with HER2
expression based on pre-defined criteria
+ HER2+ (IHC 3+ OR IHC 2+ / ISH+):
12.3% weighted avg
(6 studies, N = 971 pts)
+ HER2 low (IHC 2+/ISH- OR IHC 1+):
47.9% weighted avg
(4 studies, N = 275 pts)
Data onside courtesy of Vadim Koshkin rom: Scherrer E, ot a Front Oncol 2022:12:101 1886. PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
HER2 Expression in Primary Urothelial Bladder Cancer
Resection Samples Using Standardized Laboratory Methods
+ HER2 expression in n = 362 surgical UC samples using a standardized protocol
+ Samples were commercially sourced, paraffin-embedded primary UC resections evaluated by trained readers for HER2
expression
Methods!
— VENTANA HER2/neu (485) Rabbit Monoclonal Primary Antibody IHC assay used
- For HER2 gene amplification, used VENTANA HER2 Dual ISH DNA Probe Cocktail that detects both ERBB2
and its residing chromosome (17). HER2 gene amplification defined by HER2/Chr17 ratio 22.0
= HERZ IHC staining scored based on an established algorithm for gastric cancer
Pe of Samples N (row
Fe % CI) Stage
HER2+ HER2ow HERZz0r0
HER2+ and HER2 low 160 442 (602403) mor 7 100 0 es)
HER2#/overexpression 57 157 (124-199) Stagell 133 17(13) 46(35) 70 (63)
Stage 182 37(19) 50 (26) 102 (65)
HER2 How 103 28.5 (24.1-33.3) me eu Le)
Stage IV 30 2m 7) 21 (70)
HER a sara) All 362 S7(1G) 103(28) 202(5%)
1. Koshkin VS etal. J Cin Oncol, 2028:41 (suppl 6; abstract 556). PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, Peerview
Resection Samples Using Standardized Laboratory Methods
+ HER2 expression in n = 362 surgical UC samples using a standardized protocol
+ Samples were commercially sourced, paraffin-embedded primary UC resections evaluated by trained readers for HER2
expression
Methods!
— VENTANA HER2/neu (485) Rabbit Monoclonal Primary Antibody IHC assay used
- For HER2 gene amplification, used VENTANA HER2 Dual ISH DNA Probe Cocktail that detects both ERBB2
and its residing chromosome (17). HER2 gene amplification defined by HER2/Chr17 ratio 22.0
= HERZ IHC staining scored based on an established algorithm for gastric cancer
Pe of Samples N (row
Fe % CI) Stage
HER2+ HER2ow HERZz0r0
HER2+ and HER2 low 160 442 (602403) mor 7 100 0 es)
HER2#/overexpression 57 157 (124-199) Stagell 133 17(13) 46(35) 70 (63)
Stage 182 37(19) 50 (26) 102 (65)
HER2 How 103 28.5 (24.1-33.3) me eu Le)
Stage IV 30 2m 7) 21 (70)
HER a sara) All 362 S7(1G) 103(28) 202(5%)
1. Koshkin VS etal. J Cin Oncol, 2028:41 (suppl 6; abstract 556). PeerView.com
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Disappointing Early Results With HER2 Targeted Therapy
in Urothelial Bladder Cancer
Trastuzumab, Paclitaxel, Carboplatin, and Gemcitabine in
Advanced Human Epidermal Growth Factor Receptor-2/neu-
Positive Urothelial Carcinoma: Results of a Multicenter
Phase II National Cancer Institute Trial
Maha HA, Husain, Gay. Mac, Dani Peak, Rodney L Dunn Uk Va
‘Prima N Lara, Calar Cara, David M. Nana, L Mich lade, Donald. Tramp, een Che.
nd Did € Sth
+ Her2/neu overexpression selected by IHC,
gene amplification or elevated serum levels
+ 31/44 (70%) ORR!
+ 22.7% with grade 1-3 cardiotoxicity
« 3/9 (33%) ORR with HER2 amplified urothelial
carcinoma in a trastuzumab/pertuzumab
basket trial?
+ Other HER2 targeted drugs tested in
bladder cancer?
- DN24-02
- Lapatinib
- Afatinib
+ 2ADC basket trials with Ado-trastuzumab
emtansine (T-DM1) and bladder cancer
cohorts
- KAMELEON (NCT02999672):
HER2 overexpression
- MSKCCC (NCT02675829):
HER amplified or mutated
1 Hussain MH etal. J Gin Oncol 2007.25:2218-24. 2. Bryce AH et al. Cin Oncol, 2017.35 (suppl 6S; abstract 348) 3. Koshkin V et a. Bladder Concur. 2011-12. Peer View.com
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in Urothelial Bladder Cancer
Trastuzumab, Paclitaxel, Carboplatin, and Gemcitabine in
Advanced Human Epidermal Growth Factor Receptor-2/neu-
Positive Urothelial Carcinoma: Results of a Multicenter
Phase II National Cancer Institute Trial
Maha HA, Husain, Gay. Mac, Dani Peak, Rodney L Dunn Uk Va
‘Prima N Lara, Calar Cara, David M. Nana, L Mich lade, Donald. Tramp, een Che.
nd Did € Sth
+ Her2/neu overexpression selected by IHC,
gene amplification or elevated serum levels
+ 31/44 (70%) ORR!
+ 22.7% with grade 1-3 cardiotoxicity
« 3/9 (33%) ORR with HER2 amplified urothelial
carcinoma in a trastuzumab/pertuzumab
basket trial?
+ Other HER2 targeted drugs tested in
bladder cancer?
- DN24-02
- Lapatinib
- Afatinib
+ 2ADC basket trials with Ado-trastuzumab
emtansine (T-DM1) and bladder cancer
cohorts
- KAMELEON (NCT02999672):
HER2 overexpression
- MSKCCC (NCT02675829):
HER amplified or mutated
1 Hussain MH etal. J Gin Oncol 2007.25:2218-24. 2. Bryce AH et al. Cin Oncol, 2017.35 (suppl 6S; abstract 348) 3. Koshkin V et a. Bladder Concur. 2011-12. Peer View.com
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Trastuzumab Deruxtecan (T-DXd): An Anti-HER2 ADC
Humanized anti Ea
Ea mAb T-DXd
Highly potent ne
+ Payload MOA: topoisomerase |
inhibitor
+ High potency of payload
+ High DAR: ~8
« Payload with short systemic
half-life
a y À + Stable linker payload
E: $ Rt 268
3 A + Tumor-selective cleavable linker
+ Bystander antitumor effect
(seas)
re) Bun Ds {inhibitor payload
(OXd = DX-8951f derivative
1. Nakada T ot al. Chom Pharm Bul Tokyo). 201987:173-185. 2. Optani et al. Cin Cancor Res. 201622 5097-5108. ñ
3. Tral PA ot al. Phammacol Thor. 2018;181:126-142. 4. Okamoto H et al. Xenabotca. 2020:50:1242-1250. 5. Nag etal. Xenobiotica. 2019:49:1086-1098. PeerView.com
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Humanized anti Ea
Ea mAb T-DXd
Highly potent ne
+ Payload MOA: topoisomerase |
inhibitor
+ High potency of payload
+ High DAR: ~8
« Payload with short systemic
half-life
a y À + Stable linker payload
E: $ Rt 268
3 A + Tumor-selective cleavable linker
+ Bystander antitumor effect
(seas)
re) Bun Ds {inhibitor payload
(OXd = DX-8951f derivative
1. Nakada T ot al. Chom Pharm Bul Tokyo). 201987:173-185. 2. Optani et al. Cin Cancor Res. 201622 5097-5108. ñ
3. Tral PA ot al. Phammacol Thor. 2018;181:126-142. 4. Okamoto H et al. Xenabotca. 2020:50:1242-1250. 5. Nag etal. Xenobiotica. 2019:49:1086-1098. PeerView.com
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DESTINY-PanTumor02:
T-DXd in HER2-Expressing Solid Tumors15.a
‘An open-label, multicenter study (NCT04482309)
Sy? Endometrial cancer
Key Eligibility Criteria aa > ana
Advanced sold tumors not eligible for curative therapy V confirmed ORR
2L+ patient population Toxg M9? Ovarian cancer (investigator)
HER2 expression (IHC 3+ or 2+) 4 mola Secondary endpoints:
- Local ntral test by HercepTe » 2 DOR, DCR, PFS, OS,
not feasible (ASCOICAP gastric cancer scoring) safety
Prior HER2-t therapy allows + Exploratory analysis:
ECOGWHO PS 0-1 Biliary tract cancer subgroup analysis by
HER2 status
Pancreatic cancer
+ 267 patients received treatment; 202 (75.7%) based on local HER2 testing
= 111 (41.6%) patients were IHC 3+ based on HER? test (local or central) at enrollment; primary efficacy analysis (all patients)
~ 75 (28.1%) patients were IHC 3+ on central testing; sensitivity analysis on efficacy endpoints (subgroup analyses)
+ Median age was 62 years (23-85), and 109 (40.8%) patients had received 23 lines of therapy
+ Primary analysis data culo June 8, 2023, median fotow-up. 12.75 mo.» Patents were eigbe for ihr los Al paints were canal confirmed
| Planned werent, cohorts wih no objective responses inte rst 15 patients wore 10 be dosed. «Patients with tumors that express HERZ, excluding tumors inthe
tumor-specific cohorts, and breast cancer, NSCLC, gastic cancer, and CRC.
1. ps etnias gowstudyNNCTO4482309, 2. Hofmann Met a Hitopathology. 2008.52 797-205. 3. Merc-Bemstam F tal. ESMO 2023, Abstract LEA ñ
4. Merc Bemstam Fetal. J Gin Oncol. 2024:42:47-58. 5, Wysock et al. ASCO 2024 Absirac 4565. PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
T-DXd in HER2-Expressing Solid Tumors15.a
‘An open-label, multicenter study (NCT04482309)
Sy? Endometrial cancer
Key Eligibility Criteria aa > ana
Advanced sold tumors not eligible for curative therapy V confirmed ORR
2L+ patient population Toxg M9? Ovarian cancer (investigator)
HER2 expression (IHC 3+ or 2+) 4 mola Secondary endpoints:
- Local ntral test by HercepTe » 2 DOR, DCR, PFS, OS,
not feasible (ASCOICAP gastric cancer scoring) safety
Prior HER2-t therapy allows + Exploratory analysis:
ECOGWHO PS 0-1 Biliary tract cancer subgroup analysis by
HER2 status
Pancreatic cancer
+ 267 patients received treatment; 202 (75.7%) based on local HER2 testing
= 111 (41.6%) patients were IHC 3+ based on HER? test (local or central) at enrollment; primary efficacy analysis (all patients)
~ 75 (28.1%) patients were IHC 3+ on central testing; sensitivity analysis on efficacy endpoints (subgroup analyses)
+ Median age was 62 years (23-85), and 109 (40.8%) patients had received 23 lines of therapy
+ Primary analysis data culo June 8, 2023, median fotow-up. 12.75 mo.» Patents were eigbe for ihr los Al paints were canal confirmed
| Planned werent, cohorts wih no objective responses inte rst 15 patients wore 10 be dosed. «Patients with tumors that express HERZ, excluding tumors inthe
tumor-specific cohorts, and breast cancer, NSCLC, gastic cancer, and CRC.
1. ps etnias gowstudyNNCTO4482309, 2. Hofmann Met a Hitopathology. 2008.52 797-205. 3. Merc-Bemstam F tal. ESMO 2023, Abstract LEA ñ
4. Merc Bemstam Fetal. J Gin Oncol. 2024:42:47-58. 5, Wysock et al. ASCO 2024 Absirac 4565. PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
T-DXd: Responses Across Tumor Types‘?
80
Confirmed ORR by
igator, %
40 13 17
Median DOR, 14
‘months (95% CI) (4.4, NR)
All Pationts (N = 267) THC 3¢ (n = 75) IHC 2+ (n = 125)
‘ORR, % (95% Cl) 97.4 (813,432) 61.3 (49.4, 724) 27.2 (196, 359)
‘Median DOR, months (95% Cl) 11.3 (86, 178) 22.1 (2, NR) 98 (4.3, 126)
“Responses inthe other tumors cohort nude responses in extramammary Paget disease, oropharyngeal neoplasm, head and neck cancer and salvary gana cancer. a
1. Meri-Bemstam F etal. J Gin Oncol. 2023; 42:47-58. 2. Wysocki e al. ASCO 2024 Abstract 4565. PeerView.com
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80
Confirmed ORR by
igator, %
40 13 17
Median DOR, 14
‘months (95% CI) (4.4, NR)
All Pationts (N = 267) THC 3¢ (n = 75) IHC 2+ (n = 125)
‘ORR, % (95% Cl) 97.4 (813,432) 61.3 (49.4, 724) 27.2 (196, 359)
‘Median DOR, months (95% Cl) 11.3 (86, 178) 22.1 (2, NR) 98 (4.3, 126)
“Responses inthe other tumors cohort nude responses in extramammary Paget disease, oropharyngeal neoplasm, head and neck cancer and salvary gana cancer. a
1. Meri-Bemstam F etal. J Gin Oncol. 2023; 42:47-58. 2. Wysocki e al. ASCO 2024 Abstract 4565. PeerView.com
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T-DXd: Responses Across Tumor Types‘?
DOR in patients with an objective response,
according to tumor
+ Centrally tested as IHC 3+
Endometrial cancer
Cervical cancer
120 I Ovarian cancer.
100 1 Bladder cancer
Ë © Other tumors
3
Ex o A End of response
Ego = Patient with CR
ss 1m Endometial cancer
33” I Cervical cancer
500 AM Ovarian cancer
SE m Blaser cancer
Sin
É
Z 0 1m Pancreatic cancer
= 0
-100 !
Pane 0 3 6 9 12 15 18 21 24 27 30 33 36
Time, mo
1. Mario Bemstam F etal. Cin Oncol. 2028; 4247-58. 2. Wysock et al. ASCO 2024 Abstract 4565. PeerView.com
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Copyright © 2000-2024, PeerView
DOR in patients with an objective response,
according to tumor
+ Centrally tested as IHC 3+
Endometrial cancer
Cervical cancer
120 I Ovarian cancer.
100 1 Bladder cancer
Ë © Other tumors
3
Ex o A End of response
Ego = Patient with CR
ss 1m Endometial cancer
33” I Cervical cancer
500 AM Ovarian cancer
SE m Blaser cancer
Sin
É
Z 0 1m Pancreatic cancer
= 0
-100 !
Pane 0 3 6 9 12 15 18 21 24 27 30 33 36
Time, mo
1. Mario Bemstam F etal. Cin Oncol. 2028; 4247-58. 2. Wysock et al. ASCO 2024 Abstract 4565. PeerView.com
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T-DXd: PFS and OS in Bladder Cohort’?
10
those T4 30-4119)
Fos
5 nz 78 2016 110199
gos Total 194297, 412454,
Eu
Lo ioe enr ozs
à os 6 5 ee 6 à à
os 6 na 8 % à
Time Since First Dose, mo Time Since First Dose, mo
No. at Risk
Badder cancer 16 12 9 6
nie 2% M 1 8
Badder cancer Ta E 2 M
Per cancer MC 16 M 13 M 9 6 5 4
Baddercancer oz 2 m 7 16 1 9 7 5
10 Baddercancer Tol 4 M M 2% 2 0
+ Across all cohorts, the median PFS was 6.9 mo Across all cohorts, the median OS was 13.4 mo
* MPFS in the Bladder cohort was 7.0 mo mOS in the Bladder cohort was 12.8mo
7.8 mo for IHC2+, 7.4 mo for IHC3+ - 13.1mo for IHC2+, 13.4 mo for IHC3+
1. Mer-Bemstam F et al. J Cin Oncol 2023; 4247-58. 2. Wysocki tal. ASCO 2024 Abstract 4565, PeerView.com
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10
those T4 30-4119)
Fos
5 nz 78 2016 110199
gos Total 194297, 412454,
Eu
Lo ioe enr ozs
à os 6 5 ee 6 à à
os 6 na 8 % à
Time Since First Dose, mo Time Since First Dose, mo
No. at Risk
Badder cancer 16 12 9 6
nie 2% M 1 8
Badder cancer Ta E 2 M
Per cancer MC 16 M 13 M 9 6 5 4
Baddercancer oz 2 m 7 16 1 9 7 5
10 Baddercancer Tol 4 M M 2% 2 0
+ Across all cohorts, the median PFS was 6.9 mo Across all cohorts, the median OS was 13.4 mo
* MPFS in the Bladder cohort was 7.0 mo mOS in the Bladder cohort was 12.8mo
7.8 mo for IHC2+, 7.4 mo for IHC3+ - 13.1mo for IHC2+, 13.4 mo for IHC3+
1. Mer-Bemstam F et al. J Cin Oncol 2023; 4247-58. 2. Wysocki tal. ASCO 2024 Abstract 4565, PeerView.com
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Focus on Patients With HER2 mUC Mutations:
T-DXd Monotherapy From DESTINY-PanTumor011
ORR»
All patients 102 30
Tumor type
Patients with advanced
solid tumors harboring
prespecified HER2
mutations
\ E
Progressed on previous Small intestinal AC. 5 o =
: Cervical 3 2 667
systemic therapy Endometrial 2 2 100
Other neuroendocrine 2 + 5
Pancreat 2 6 =
Trastuzumab ‘AC ol unknown primary + 1 too
Deruxtecan 5.4 mg/kg Extramammary Paget's disease 1 1 100
Melanoma 1 o 0
Q3w Ovarian 1 o 0
Urachal 1 o. 0
HER2m domain
Tyrosine kinase 5 9 905
Extraceltlar “m 24 .
1.LIBTetal. Ann Oncol. 2023; 34 (suppl 2):5459-5460. Transmembraneljuxtamembrane 17 1 59 PeerView.com
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T-DXd Monotherapy From DESTINY-PanTumor011
ORR»
All patients 102 30
Tumor type
Patients with advanced
solid tumors harboring
prespecified HER2
mutations
\ E
Progressed on previous Small intestinal AC. 5 o =
: Cervical 3 2 667
systemic therapy Endometrial 2 2 100
Other neuroendocrine 2 + 5
Pancreat 2 6 =
Trastuzumab ‘AC ol unknown primary + 1 too
Deruxtecan 5.4 mg/kg Extramammary Paget's disease 1 1 100
Melanoma 1 o 0
Q3w Ovarian 1 o 0
Urachal 1 o. 0
HER2m domain
Tyrosine kinase 5 9 905
Extraceltlar “m 24 .
1.LIBTetal. Ann Oncol. 2023; 34 (suppl 2):5459-5460. Transmembraneljuxtamembrane 17 1 59 PeerView.com
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What About a Combination Approach?!
Key Eligibility Criteria
Advanced/metastatic HER2-
expressing breast or urothelial
cancer
ECOG 0-1
measurable lesion per RECIST
11
No prior T-DXd or Nivo
cohorts in part 2
Part 1: Dose Escalation
Part 2: Dose Expansion
3+3+3design
‘ohort 1: HER2-positive
(HC 3+ or IHC 2+/18H+) BC post-T-DM1
"Cohort 2: HERZIOW
(IHC 1+ or IHC 2+18H-) BC post standard
treatment
n=16
Gohort 3: HERZ-hIgh expressing
(HC 2+/3+) urothelial cancer post-Ctx and 10
naive
= 30 (planned)
Cohort 4: HER2dow (IHC 14) urothelial cancer.
post Ctx and IO treatment naive
= 15 (planned) (Only enrolled n = 4)
"Three patients wore HER2-postive, 1 was HER2-ow. AI patients were HER2-postive.
1. Galsky MD et al. J Clin Oncol 2022:40(suppl6)438-438. PeerView.com
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Key Eligibility Criteria
Advanced/metastatic HER2-
expressing breast or urothelial
cancer
ECOG 0-1
measurable lesion per RECIST
11
No prior T-DXd or Nivo
cohorts in part 2
Part 1: Dose Escalation
Part 2: Dose Expansion
3+3+3design
‘ohort 1: HER2-positive
(HC 3+ or IHC 2+/18H+) BC post-T-DM1
"Cohort 2: HERZIOW
(IHC 1+ or IHC 2+18H-) BC post standard
treatment
n=16
Gohort 3: HERZ-hIgh expressing
(HC 2+/3+) urothelial cancer post-Ctx and 10
naive
= 30 (planned)
Cohort 4: HER2dow (IHC 14) urothelial cancer.
post Ctx and IO treatment naive
= 15 (planned) (Only enrolled n = 4)
"Three patients wore HER2-postive, 1 was HER2-ow. AI patients were HER2-postive.
1. Galsky MD et al. J Clin Oncol 2022:40(suppl6)438-438. PeerView.com
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What About a Combination Approach?!
T-DXd + nivolumab in Cohort 3: HER2-high expressing (IHC 2+/3+)
œ
ge ©
ee
si =»
Be a ORR 36.7%
og median DOR 13.1 mo
Be » median PFS 6.9 mo
sE > median OS 11.1 mo
25
ES ©
»
Cohort 31HC3+/2+ (n = 30) (part 2: T:DXd 5.4 mg/kg and nivolumab 360 mg)
‘Bost (minimum) percentage change
= oo an i tax
ES 7 mas 220 109 8
1. Galsky MD at al. J Cin Oncol, 2022:40(suppl 6)438-438. PeerView.com
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T-DXd + nivolumab in Cohort 3: HER2-high expressing (IHC 2+/3+)
œ
ge ©
ee
si =»
Be a ORR 36.7%
og median DOR 13.1 mo
Be » median PFS 6.9 mo
sE > median OS 11.1 mo
25
ES ©
»
Cohort 31HC3+/2+ (n = 30) (part 2: T:DXd 5.4 mg/kg and nivolumab 360 mg)
‘Bost (minimum) percentage change
= oo an i tax
ES 7 mas 220 109 8
1. Galsky MD at al. J Cin Oncol, 2022:40(suppl 6)438-438. PeerView.com
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Tumor-Agnostic FDA Approval for T-DXd!3
Updated NCCN Guidelines for
Bladder Cancer!
Second- or subsequent-line therapy:
T-DXd added for HER2-positive tumors (IHC 3+ or 2+)
Useful in certain circumstances
Accelerated FDA Approval?
For adult patients with unresectable or metastatic HER2-positive (IHC3+)
solid tumors who have received prior systemic treatment and have no
satisfactory alternative treatment options
1. NCCN Bladder Concer Guidoines VA 2024. tos wwtncen oryrotossionals physician l/piadgor pl.
2 Mis www da gowdrugtresoureesnformaton-approved-druge/sa-grants-acceltated-dpprovaarmratuzumab-dorutecan-oxk-unvesectabie-o-metastasc- a
her. 3. ENHERTU (lam rastuzumab derustecan-nki) Prescribing Information. hits:/www accossdata da govugsatiéa_ docs/abel2024/761130028m pe. PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
Updated NCCN Guidelines for
Bladder Cancer!
Second- or subsequent-line therapy:
T-DXd added for HER2-positive tumors (IHC 3+ or 2+)
Useful in certain circumstances
Accelerated FDA Approval?
For adult patients with unresectable or metastatic HER2-positive (IHC3+)
solid tumors who have received prior systemic treatment and have no
satisfactory alternative treatment options
1. NCCN Bladder Concer Guidoines VA 2024. tos wwtncen oryrotossionals physician l/piadgor pl.
2 Mis www da gowdrugtresoureesnformaton-approved-druge/sa-grants-acceltated-dpprovaarmratuzumab-dorutecan-oxk-unvesectabie-o-metastasc- a
her. 3. ENHERTU (lam rastuzumab derustecan-nki) Prescribing Information. hits:/www accossdata da govugsatiéa_ docs/abel2024/761130028m pe. PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
DESTINY-PanTumor02: T-DXd Safety Findings‘?
Bladder Cancer
Adverse Ever (n= 41)
Drug-related adverse
7 38 (92.7)
sente NC) Most common overall >Grade 3 TRAEs were
Grade 23 17 (41.5) neutropenia and anemia
Serious adverse events 4 (9.8) A risk of pulmonary adverse events, primarily
Leading to ILD/pneumonitis, has been observed in patients
discontinuation 4098) receiving T-DXd and team-based management is key
Leading to dose
modification ab (ee)
Associated with death 1 (2.4)
1. Meti-Bemstam F etal. J Gin Oncol. 2028; 42:47-58. 2. Wysocki et al. ASCO 2024 Abstract 4565. PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
Bladder Cancer
Adverse Ever (n= 41)
Drug-related adverse
7 38 (92.7)
sente NC) Most common overall >Grade 3 TRAEs were
Grade 23 17 (41.5) neutropenia and anemia
Serious adverse events 4 (9.8) A risk of pulmonary adverse events, primarily
Leading to ILD/pneumonitis, has been observed in patients
discontinuation 4098) receiving T-DXd and team-based management is key
Leading to dose
modification ab (ee)
Associated with death 1 (2.4)
1. Meti-Bemstam F etal. J Gin Oncol. 2028; 42:47-58. 2. Wysocki et al. ASCO 2024 Abstract 4565. PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
Detecting and Managing T-DXd-Related ILD:
The Five “S” Rules!
Gc
cs
1 ja 2
Download the
Practice Aid
learn more about
ADC Safety
Management
Screen Scan Synergy Suspend Steroids
Treatment
+ Careful patient | + The fundamental + Minimizing the risk + T-DXd should always ||| + The mainstay for
‘selection is warranted diagnostic tools for of ILD involves be interrupted if ILD is treating T-DXd—
before initiating T-DXd ILD remain teamwork, which ‘suspected; it can only induced ILD remains
to optimize the radiological scans, includes educating be restarted in the corticosteroids, with
monitoring strategies with preference for patients and all the case of asymptomatic the dose adapted to.
based on baseline risk ||| high-resolution CT care team, as well ILD that fully resolves the toxicity grade
+ Screening continues ‘scans of the chest as multidisciplinary
during treatment, + Abaseline scan is management once
with regular clinical recommended, with ILD is suspected
assessments to repeat scans to be
exclude signs/ performed
‘symptoms of ILD 6-12 weeks
1. Tarantino P, Tolanoy SM. JCO Oncol Prat. 2023:19:526-627.
PeerView.com/MBD827
PeerView.com
Copyright © 2000-2024, PeerView
The Five “S” Rules!
Gc
cs
1 ja 2
Download the
Practice Aid
learn more about
ADC Safety
Management
Screen Scan Synergy Suspend Steroids
Treatment
+ Careful patient | + The fundamental + Minimizing the risk + T-DXd should always ||| + The mainstay for
‘selection is warranted diagnostic tools for of ILD involves be interrupted if ILD is treating T-DXd—
before initiating T-DXd ILD remain teamwork, which ‘suspected; it can only induced ILD remains
to optimize the radiological scans, includes educating be restarted in the corticosteroids, with
monitoring strategies with preference for patients and all the case of asymptomatic the dose adapted to.
based on baseline risk ||| high-resolution CT care team, as well ILD that fully resolves the toxicity grade
+ Screening continues ‘scans of the chest as multidisciplinary
during treatment, + Abaseline scan is management once
with regular clinical recommended, with ILD is suspected
assessments to repeat scans to be
exclude signs/ performed
‘symptoms of ILD 6-12 weeks
1. Tarantino P, Tolanoy SM. JCO Oncol Prat. 2023:19:526-627.
PeerView.com/MBD827
PeerView.com
Copyright © 2000-2024, PeerView
Disitamab Vedotin
Humanized anti-HER2 Protease-cleavable vc Microtubule-disrupting agent,
1gG1 mAb maleimidocaproyl linker re
ou on vaine
Male Capri ac Les
OF NH,
Maleimidocaproy! Valine Cirutine MMAE
Hertuzumab
PeerView.com
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Humanized anti-HER2 Protease-cleavable vc Microtubule-disrupting agent,
1gG1 mAb maleimidocaproyl linker re
ou on vaine
Male Capri ac Les
OF NH,
Maleimidocaproy! Valine Cirutine MMAE
Hertuzumab
PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
Disitamab Vedotin Monotherapy*?
‚Activity in HER2 2-3+
Target Lesion Change From Baseline
ORR = 50.5% (54/107)
IHC3+ HERZ 1HC2+ and
FISH.
388582
0
10
Percent Change From Baseline, %
88588
‚Activity in HER2 1+
m co
wine
63% had 2 prior lines to tx
Percent Change From Basel
70] ORR
80 | IHC2+FISH+ or IHC3+ (n = 45) = 62.2%
720 ] IHC2+FISH- (n = 53) = 39.6%
‘No.of Prior Systemic Therapies, n(%) ‘ORR = 26.3% (5/19)
On 1 ne 385)
22ines 69645)
1. Sheng X et al. J Clin Onco 2022404518. 2. Sheng X eta. J Cin Oncol. 2024:42:1991-1402. 3. Xu H etal. J Cin Oncol. 2022:40:4519, PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
‚Activity in HER2 2-3+
Target Lesion Change From Baseline
ORR = 50.5% (54/107)
IHC3+ HERZ 1HC2+ and
FISH.
388582
0
10
Percent Change From Baseline, %
88588
‚Activity in HER2 1+
m co
wine
63% had 2 prior lines to tx
Percent Change From Basel
70] ORR
80 | IHC2+FISH+ or IHC3+ (n = 45) = 62.2%
720 ] IHC2+FISH- (n = 53) = 39.6%
‘No.of Prior Systemic Therapies, n(%) ‘ORR = 26.3% (5/19)
On 1 ne 385)
22ines 69645)
1. Sheng X et al. J Clin Onco 2022404518. 2. Sheng X eta. J Cin Oncol. 2024:42:1991-1402. 3. Xu H etal. J Cin Oncol. 2022:40:4519, PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
What About a Combination Approach?!
Disitamab Vedotin + Toripalimab
100 HERZ Stats
3 Confirmed ORR = 71.8% (28/39) HERO MHERI
so (CR 3. PR 25) SHER FER gap
32 5 ©
so g 7
ä 40 zo
EX 3%
20 3%
E 10 2
8 2 ES
z E
5% 33
= 30
5 = 40
in 2%
Ez E
80 8
4 30
e & 40
Prior Systeme Treatment, (4)
ote 25,6088)
aires 105902)
4. Sheng X tal. J Cin Oncol. 2022:40:4520. PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
Disitamab Vedotin + Toripalimab
100 HERZ Stats
3 Confirmed ORR = 71.8% (28/39) HERO MHERI
so (CR 3. PR 25) SHER FER gap
32 5 ©
so g 7
ä 40 zo
EX 3%
20 3%
E 10 2
8 2 ES
z E
5% 33
= 30
5 = 40
in 2%
Ez E
80 8
4 30
e & 40
Prior Systeme Treatment, (4)
ote 25,6088)
aires 105902)
4. Sheng X tal. J Cin Oncol. 2022:40:4520. PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
What About a Combination Approach?1
Phase 2: Disitamab Vedotin + Pembrolizumab
Cohort A
HER2+
DV Monotherapy
Key Eligibility Criteria
agents or MM
+ 1-2 lines of prior DV + pembro Primary endpoint:
platinum-containing 50) CORR by BICR
therapy for cohorts,
B, and no prior LA/MUC Single arm DV +
therapy for cohort € 2 pembro
DV Monotherapy
*Hstologiasy confirmed, including UC oriinaing rom the renal pelvis, ureters, ladder, or reta, PR
1. its Aw cimicaltnals.gov/studyNCTO4879328. PeerView.com
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Phase 2: Disitamab Vedotin + Pembrolizumab
Cohort A
HER2+
DV Monotherapy
Key Eligibility Criteria
agents or MM
+ 1-2 lines of prior DV + pembro Primary endpoint:
platinum-containing 50) CORR by BICR
therapy for cohorts,
B, and no prior LA/MUC Single arm DV +
therapy for cohort € 2 pembro
DV Monotherapy
*Hstologiasy confirmed, including UC oriinaing rom the renal pelvis, ureters, ladder, or reta, PR
1. its Aw cimicaltnals.gov/studyNCTO4879328. PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, Peerview
What About a Combination Approach?1
An Open-label, Randomized, Controlled Phase 3 Study of Disitamab Vedotin in Combination
With Pembrolizumab Versus Chemotherapy in Subjects with Previously Untreated Locally
Advanced or Metastatic Urothelial Carcinoma that Expresses HER2 (IHC 1+ and Greater)
DV + Pembrolizumab
Key Eligibility Criteria
LAmU Dual-Primary Endpoints:
Previously untre .
Eligible for platinum PFS by BICR
+ Central lab HER2 + OS
status 2 IHC 1+
rboplatin + Gemcitabine
289 sites in 30 countries globally app
+ US, Canada, LATAM, EU, Israel, Turkey, APAC
+ Competitive enrollment; no site/country cap
+ Estimated enrollment start & end date
= FPI: Q3 2023
- LPI: Qt 2026
‘Maintenance therapy in te 1L seing as ciicaly appropriate and local} approved is allowed. Avelumab wil not be provided by sponsor." DV 1.5 mghg Q2W untl
‘disease progression and pembrolzumab 400 mg QW for up to 18 cycles, =
1. ips icincatiatsgovistudyINCTOSO1 1295. PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
An Open-label, Randomized, Controlled Phase 3 Study of Disitamab Vedotin in Combination
With Pembrolizumab Versus Chemotherapy in Subjects with Previously Untreated Locally
Advanced or Metastatic Urothelial Carcinoma that Expresses HER2 (IHC 1+ and Greater)
DV + Pembrolizumab
Key Eligibility Criteria
LAmU Dual-Primary Endpoints:
Previously untre .
Eligible for platinum PFS by BICR
+ Central lab HER2 + OS
status 2 IHC 1+
rboplatin + Gemcitabine
289 sites in 30 countries globally app
+ US, Canada, LATAM, EU, Israel, Turkey, APAC
+ Competitive enrollment; no site/country cap
+ Estimated enrollment start & end date
= FPI: Q3 2023
- LPI: Qt 2026
‘Maintenance therapy in te 1L seing as ciicaly appropriate and local} approved is allowed. Avelumab wil not be provided by sponsor." DV 1.5 mghg Q2W untl
‘disease progression and pembrolzumab 400 mg QW for up to 18 cycles, =
1. ips icincatiatsgovistudyINCTOSO1 1295. PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
DV Safety’
TRAE Grade 1, No. (
Gamma-glutamyitransferase increased
Pruritus.
Vomit
2 TRAES (> 15%) nal patents; no grade 5 events occured.
1.Shong X at al J Clin Oncol 2024 42:1981-1402,
PeerView.com/MBD827
13021)
35 (92.7)
19 (17.8)
39 (264)
13 (121)
37 (46)
26 (243)
31 290)
30 (280)
27 (252)
16(150)
14 (13.1)
21 (196)
17 (152)
12(112)
768)
130121)
16 (150)
Grade 2, No. (%)
26 (33.6)
18168)
33908)
5(47)
19178)
san
124112)
765)
3(28)
407)
41 (103)
12012)
328)
san
805)
984)
765)
2(19)
Grade 3, No. (
5614)
200187)
2(19)
109)
12(112)
109)
4@7)
0
109)
0
o
o
o
109)
328)
666)
109)
109)
Grade 4, No.
30
10:
B 00000000
oo oo
8)
9)
Total (1 107), n (%
107 (100.0)
73 (68.2)
54 (50.5)
45 (42.1)
45 (421)
43402)
42(393)
38 (855)
34318)
31 (29.0)
27 (25.2)
26 (24:3)
24 (224)
24 (22.4)
23 (215)
22 (20.6)
211186)
19 (178)
PeerView.com
Copyright © 2000-2024, PeerView
TRAE Grade 1, No. (
Gamma-glutamyitransferase increased
Pruritus.
Vomit
2 TRAES (> 15%) nal patents; no grade 5 events occured.
1.Shong X at al J Clin Oncol 2024 42:1981-1402,
PeerView.com/MBD827
13021)
35 (92.7)
19 (17.8)
39 (264)
13 (121)
37 (46)
26 (243)
31 290)
30 (280)
27 (252)
16(150)
14 (13.1)
21 (196)
17 (152)
12(112)
768)
130121)
16 (150)
Grade 2, No. (%)
26 (33.6)
18168)
33908)
5(47)
19178)
san
124112)
765)
3(28)
407)
41 (103)
12012)
328)
san
805)
984)
765)
2(19)
Grade 3, No. (
5614)
200187)
2(19)
109)
12(112)
109)
4@7)
0
109)
0
o
o
o
109)
328)
666)
109)
109)
Grade 4, No.
30
10:
B 00000000
oo oo
8)
9)
Total (1 107), n (%
107 (100.0)
73 (68.2)
54 (50.5)
45 (42.1)
45 (421)
43402)
42(393)
38 (855)
34318)
31 (29.0)
27 (25.2)
26 (24:3)
24 (224)
24 (22.4)
23 (215)
22 (20.6)
211186)
19 (178)
PeerView.com
Copyright © 2000-2024, PeerView
Take-Home Points
HER2 expression is not uncommon for urothelial bladder cancer
Antibody drug conjugates offer an exciting technology that recently has shown
clinical efficacy in many cancers, including bladder cancer
HERZ is being revisited as a promising drug target for patients with urothelial
bladder cancer
Promising examples of ADCs for bladder cancer that target HER2 include T-DXd
and DV, both as monotherapy and in combination with checkpoint inhibitors
T-DXd has an FDA-accelerated approval for adult patients with unresectable
or metastatic HER2-positive (IHC3+) solid tumors who have received prior
systemic treatment and have no satisfactory alternative treatment options
PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
HER2 expression is not uncommon for urothelial bladder cancer
Antibody drug conjugates offer an exciting technology that recently has shown
clinical efficacy in many cancers, including bladder cancer
HERZ is being revisited as a promising drug target for patients with urothelial
bladder cancer
Promising examples of ADCs for bladder cancer that target HER2 include T-DXd
and DV, both as monotherapy and in combination with checkpoint inhibitors
T-DXd has an FDA-accelerated approval for adult patients with unresectable
or metastatic HER2-positive (IHC3+) solid tumors who have received prior
systemic treatment and have no satisfactory alternative treatment options
PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
Elizabeth’s Case: A 68-Year-Old
Patient With Metastatic Urothelial Cancer
Patient Case
o : 5 In developing next steps for Elizabeth, what
ao paler UNSEREN important factors should be considered?
symptomatic progression with fatigue and
back palo Would T-DXd be an appropriate choice?
How would you decide between T-DXd vs SG?
How do you educate Elizabeth on expectations
For Panel Discussion
Prior treatment/additional workup
+ Progression after 4 cycles of carbo/gem =>
maintenance avelumab (CT showed bone
mets) What baseline parameters should the care team
+ EVinitiated perform? How should they monitor her?
+ Further progression after 9 months EV
+ NGS: HER2 amplification
+ IHC: HER2+ (IHC3+)
for dosing/scheduling/AEs?
PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
Patient With Metastatic Urothelial Cancer
Patient Case
o : 5 In developing next steps for Elizabeth, what
ao paler UNSEREN important factors should be considered?
symptomatic progression with fatigue and
back palo Would T-DXd be an appropriate choice?
How would you decide between T-DXd vs SG?
How do you educate Elizabeth on expectations
For Panel Discussion
Prior treatment/additional workup
+ Progression after 4 cycles of carbo/gem =>
maintenance avelumab (CT showed bone
mets) What baseline parameters should the care team
+ EVinitiated perform? How should they monitor her?
+ Further progression after 9 months EV
+ NGS: HER2 amplification
+ IHC: HER2+ (IHC3+)
for dosing/scheduling/AEs?
PeerView.com
PeerView.com/MBD827 Copyright © 2000-2024, PeerView
Audience Q&A
Copyright © 2000-2024, PeerView
Copyright © 2000-2024, PeerView
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