Candid Conversations on Modern Urothelial Cancer Management: Personalizing Patient Care Using the Latest Evidence and Innovative Therapeutic Strategies

Chair and Presenters, Andrea Necchi, MD, Matthew D. Galsky, MD, Shilpa Gupta, MD, and Michiel S. van der Heijden, MD, PhD, discuss bladder cancer in this CME/MOC/NCPD/AAPA/IPCE activity titled “Candid Conversations on Modern Urothelial Cancer Management: Personalizing Patient Care Using the Latest Evidence and Innovative Therapeutic Strategies.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at https://bit.ly/4cDsBog. CME/MOC/NCPD/AAPA/IPCE credit will be available until June 30, 2025.

1. Candid Conversations on Modern
Urothelial Cancer Management

Personalizing Patient Care Using the Latest Evidence
and Innovative Therapeutic Strategies

Andrea Necchi, MD
Associate Professor
Vita-Salute San Raffaele University MAA

Director of GU Medical Oncology
IRCCS San Raffaele Hospital
Milan, Italy

Shilpa Gupta, MD
Clinical Professor of Medicine

Cleveland Clinic Lerner College of Medicine of CWRU
Director, Genitourinary Oncology

Cleveland Clinic Taussig Cancer Institute

Cleveland, Ohio

Matthew D. Galsky, MD |
Professor of Medicine

Icahn School of Medicine at Mount Sinai ME

Director of Genitourinary Medical Oncology >
Co-Leader, Cancer Clinical Investigation Program 4

Associate Director for Translational Research
Tisch Cancer Institute
New York, New York

Michiel S. van der Heijden, MD, PhD
Medical Oncologist

and Research Group Leader
Netherlands Cancer Institute
Amsterdam, The Netherlands

Go online to access full CME/MOC/NCPD/AAPA/IPCE information, including faculty disclosures.

Copyright © 2000-2024, Peerview

2. Disclosures

All relevant conflicts of interest have been mitigated prior to the commencement of
the activity.

Chair/Planner Catalym; Genenta science; Gilead Sciences,
Andrea Necchi, MD Inc.; Incyte; Johnson & Johnson Services, Inc.;
Associate Professor Loxo Oncology; Merck & Co., Inc.; Merck
Vita-Salute San Raffaele University Serono; Pfizer Inc.; and Seagen Inc

Director of GU Medical Oncology Grant/Research Support from AstraZeneca;
IRCCS San Raffaele Hospital Bristol Myers Squibb; Incyte; Gilead Sciences,
Milan, Italy Inc.; Merck & Co., Inc.

Andrea Necchi, MD, has a financial
interest/relationship or affiliation in the form of:

Consultant and/or Advisor for Astellas Pharma
US, Inc.; AstraZeneca; Bristol Myers Squibb;

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3. Disclosures

All relevant conflicts of interest have been mitigated prior to the commencement of

the activity.

Faculty/Planner
Matthew D. Galsky, MD

Professor of Medicine

Icahn School of Medicine at Mount Sinai

Director of Genitourinary Medical Oncology
Co-Leader, Cancer Clinical Investigation Program
Associate Director for Translational Research
Tisch Cancer Institute

New York, New York

Matthew D. Galsky, MD, has a financial
interest/relationship or affiliation in the form of:
Consultant and/or Advisor for AbbVie Inc.; Alligator
Bioscience AB; Analog Devices, Inc.; Asieris
Pharmaceuticals; AstraZeneca; Basilea

PeerView.com/GJT827

Pharmaceutica Ltd; Bicycle Therapeutics; Bristol
Myers Squibb; Curis, Inc.; Daiichi Sankyo, Inc.;
Dragonfly Therapeutics; EMD Serono; FUJIFILM
Pharmaceuticals U.S.A., Inc.; Genentech, Inc.; Gilead
Sciences, Inc.; GlaxoSmithKline; Janssen
Pharmaceuticals, Inc.; Merck & Co., Inc.; Numab
Therapeutics AG; Pfizer Inc.; Rappta Therapeutics;
Seagen Inc.; Silverback Therapeutics; UroGen
Pharma, Inc.; Veracyte, Inc.

4. Disclosures

All relevant conflicts of interest have been mitigated prior to the commencement of

the activity.

Faculty/Planner
Shilpa Gupta, MD

Clinical Professor of Medicine

Cleveland Clinic Lerner College of Medicine
of CWRU

Director, Genitourinary Oncology

Cleveland Clinic Taussig Cancer Institute
Cleveland, Ohio

Shilpa Gupta, MD, has a financial
interest/relationship or affiliation in the form of:

Consultant and/or Advisor for Astellas Pharma US,

Inc.; Bristol Myers Squibb; Foundation Medicine, Inc.;

Genzyme; Gilead Sciences, Inc.; Merck 8 Co., Inc.;
Pfizer Inc.; and Seagen Inc.

PeerView.com/GJT827

Grant/Research Support from Acrivon Therapeutics;
Bristol Myers Squibb; EMD Serono, Inc.; Exelixis,
Inc.; F. Hoffmann-La Roche Ltd; Gilead Sciences,
Inc.; Merck & Co., Inc.; Moderna, Inc.; Novartis
Pharmaceuticals Corporation; Pfizer Inc.; Seattle
Genetics; and QED Therapeutics.

Speaker for Bristol Myers Squibb and Seattle
Genetics.

Stock Shareholder in BioNTech SE. and Nektar.

5. Disclosures

All relevant conflicts of interest have been mitigated prior to the commencement of
the activity.

Faculty/Planner Inc.; Pfizer Inc.; and Seagen Inc.

Michiel S. van der Heijden, MD, PhD Grant/Research Support from AstraZeneca;
Medical Oncologist and Research Bristol Myers Squibb; F. Hoffmann-La Roche
(Chia esti, Ltd; Merck & Co., Inc.; and 4SC AG

Netherlands Cancer Institute S, f IM Sauil
‚Amsterdam, The Netherlands PROA a SEE
Michiel S. van der Heijden, MD, PhD, has a

financial interest/relationship or affiliation in the

form of:

Consultant and/or Advisor for Astellas Pharma
US, Inc.; AstraZeneca; Bristol Myers Squibb;
Janssen Pharmaceuticals, Inc.; Merck & Co.,

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6. Planning Committee and Reviewer Disclosures

Planners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education,
Bladder Cancer Advocacy Network, do not have any relevant financial relationships related to
this CE activity unless listed below.

Copyright © 2000-2024, PeerView

7. Our Goals for Today

Augment your understanding of current and emerging data for the
treatment of urothelial cancer utilizing bladder-sparing approaches,
perioperative strategies, and combination regimens

Equip you with the skills you need to implement these approaches
into personalized treatment plans

Provide you with guidance on how to support team-based
management of the unique suite of adverse events associated
with various regimens

2000-2024, PeerView

8. Modern Therapeutic Strategies for
Effective Management of NMIBC

Andrea Necchi, MD

Associate Professor

Vita-Salute San Raffaele University
Director of GU Medical Oncology
IRCCS San Raffaele Hospital
Milan, Italy

Copyright © 2000-2024, Peerview

9. BCAN Is an Excellent Resource for
Professionals, Patients, and Caregivers

When diagnosed with bladder cancer, HE
patients and their caregivers may feel
overwhelmed by the amount of treatment
BCAN. options for urothelial carcinoma.
ssééu crerasecgnemes BCAN provides educational resources to
temoin help patients feel more prepared.

In addition to giving patients and caregivers 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

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10. Moving Outside of the United States:
The World Bladder Cancer Patient Coalition’

Understanding 7 Worldwide Thotatest figures show | Biar concer roks

igre amangman. for
‘ised cancers the Wem kin

bladder cancer impact > < 10th most

cancer revere Gth =

ange

=> [3th 212,536 | gy, ==.

cause of death DEATHS in 2020 atone

N. America,
89,997
21,045

Latin America
5 Caribbean

1 htps/Ivordbiadéerancer or! PeerView.com

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11. Unmet Needs in the Treatment of NMIBC and MIBC

+ Only one-third of patients with NMIBC are given intravesical BCG"
- BCG shortages in the United States may affect access?

+ Close to half of patients with MIBC worldwide may not receive
curative-intent therapy?

+ Patients who have undergone radical cystectomy for MIBC often have
impaired HRQOL and a high risk of recurrence®5

Development of effective, safe, and durable intravesical treatment remains a
critical unmet clinical need for patients who want to avoid radical cystectomy

Effective approaches post radical cystectomy are key to lessening risk
of recurrence

4. Tyson M et a. J Gin Oncol 201937(supal 15):016012. 2. tps auanatorlaboutunbeg-choniage-no u
3. Westergren DO at al. J Ural 2019.202:908:912. 4. Chol Het a. Trans! Androl Url. 2020;8:2887-3006. 5, Roupret M e al. Eur Urol, 2021:79:62-79 PeerView.com

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12. Background
High-Risk NMIBC Is Defined as High-grade Ta, Any T1, and/or Carcinoma in situ

+ Standard of care for high-risk NMIBC: TURBT followed by intravesical BCG
+ Prognosis is poor for patients whose disease does not respond to BCG or relapses within 12 months";
these patients are directed to radical cystectomy

Criteria for the Definition of Adequate BCG and BCG-Unresponsive, High-Risk NMIBC
Are Well Established and Endorsed by the FDA?

+ Adequate BCG induction: 25 instillations of BCG and 27 instillations within 9 months of the first
instillation of induction therapy

+ BCG-unresponsive, high-risk NMIBC is defined as one of the following
— Stage progression at 3 months despite adequate BCG induction
High-grade T1 disease at first evaluation after adequate BCG induction
Persistent high-risk NMIBC at 6 months after adequate BCG
— Recurrent high-risk NMIBC within 9 months of the last BCG instillation despite adequate BCG

1

1. Joong et al. BMC Cancer. 2022.22:361. 2. Kamat AM etal. J Cin Oncol. 2016:34:1995-1944. PeerView.com

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13. Snapshot of Treatment Approaches for
High-Risk NMIBC Unresponsive to BCG

Immune checkpoint FGER inhibition via CG0070 (Cietoedimegsne)
inhibition via pembrolizumab intravesical delivery of Phase 3 BOND-003
FDA approved January 2020* erdafitinib- CG0070 + pembrolizumab

TAR-210? Phase 2 CORE1*
Sustained release of YN
gemcitabine via TAR-200

‘SunRISe-157

Viral gene transfer:

SunRiSe-3® |

Fe nadofaragene firadenovec®1
= FDA approved Dec 2022
SunRiSe-5 unresponsive
| FDA breakthrough designation NMIBC

IL-15 superagonist Gemcitabine + docetaxel

Phase 2/3 QUILT'? Y 3 Y Approach for BCG-naive'*
(N-803) | Intravesical ADC Phase 3 BRIDGE/EA8212:

FDA approved April 2024 (ere aan) BCG vs gemcitabine/docetaxel

a ESMO 2023 LBA OS 7 Jacob Joa. AUA 2024
Abstract P201. 8. Mtpslcinicalvas govistudyINCTOST14202. 9. Shore ND etal. J Gin Oncol, 2017.35:3410-3416. 10 Boorian SA et ai. Lancet Onca.

2021:22:107-147, 11. Mira AP et al. AUA 2022. Abstract MPS405, 12. Came K. NEJM Evidence. 20222. 13. Kama AM et lJ Cin Oncol. 2023:41(supe 16): 7, a

Abstract 4596. 14, McElree IM at al. J Urol 2022:208 580-599. PeerView.com

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14. KEYNOTE-057 Cohort A: Pembrolizumab Monotherapy for
BCG-Unresponsive, High-Risk NMIBC!

Cohort A: CIS + Papillary

Disease (High-Grade Ta or T1)

Patients (N = 96)

100 Best Response
Median DOR (range): a _
2 “é 16.2 (0-30.4) CR 39(40.6) 30.7-51.1
$ Non-CR 56(58.3) 47.8-68.3
Po Progression to T2 0 NA
= NE 11.0) 0-57
H 4 Upstaging to 2pT2 in 8.3% patients
2
3 2 tended minimum follow-up of 26.3 mo
é responders, 13 (33.3%) remained in CR
7 8 mo and 9 (23.1%) remained in CR 224 mo
0 3 6 8 2 % 8 A À 2 © &
Time, mo risks were identified

January 2020

Pembrolizumab was FDA approved for the treatment of patients with BCG-unresponsive, high-risk NMIBC with
carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy

1. BalarAV ot al. Lancet Oncol. 2021:22:919-030,

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15. KEYNOTE-057 Cohort B:
Pembrolizumab for Papillary High-Risk NMIBC12.

N Median (95% Cl), mo
100

90 132 7.7 (5.5-13.6)
80
70 ( Indication now included in
2 60 43.5% NCCN Guidelines, Bladder Cancer.
@ 50 Poe. Version 4.0, May 9, 2024?
LE N
ao R H
30 i '
20 H ‘
10 H ‘
oo ot ot ooo
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69
Time, mo
* Por central patologyltadioiogy review. Data cut, October 20, 2022: Median folow-up: 4 N
VENA cal Lone’ One A SO AS DES 2, hips An. noon rreiessoniphyican. Quer et. PeerView.com

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16. What’s Next? Investigational Strategies
for BCG-Unresponsive or BCG-Naive NMIBC

Phase 3 POTOMAC"
High-Risk NMIBC

Phase 3 KEYNOTE-6762

+ Any HG

+ Any Ti High-Risk NMIBC

+ Multiple, recurrent and large (>3 cm) Ta + Recurrence after induction BCG
i therapy only

+ No prior BCG therapy N 2 1405

N=1,018

BCG +
pembrolizumab

BCG BCG induction/ 1duction
induction only ff] maintenance jf + maintenance
+durvalumab | + durvalumab (24 mo)

+ Primary endpoint: DFS

+ Primary endpoint: CR in patients with CIS

1. ips IeincaRials gov'studyiNCTO3528694 2 ps cnica govistudyiNCTO37 1092.3. Gupta Set al. ASCO GU 2024. Abstract TPS722. PeerView.com

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17. SunRISe-1: TAR-200 in BCG-Unresponsive,
High-Risk NMIBC1*

TAR-200 + cetrelimab®
Cohort 4 (N

Cetrelimab® alone
Cohort 3 (N = 28)¢
Cohort 3 was cl

200 alone
hort 4 (N

+ Response is determined by quarterly cystoscopy, quarterly central cytology, and central pathology at weeks 24 and 48
and as clinically indicatede
+ The study protocol did not allow retreatment for nonresponders consistent with US FDA guidance?

Cohort 4:
Primary endpoint
DFS rate at 12 mo

The cial at tol was January 22028.
"Patents win BEG-unroeponsivePapilary-oky HR NMIBC (gh-grade Ta, any T1) per protocol amendment 4.» Cetrlmab is an ant-programmod cel death-134;

úcotrolmab dosing was through week 78.55 patents wor randomized and 53 ware Vested in cohort 1.228 patents were randomized and treated in conon 3.

imaging (CTIMR!) was petormed every 24 wooks tough your 3.

4. Lemer SP eta, Ure! Oncol 2008.27 155-159 2. tips www da govimecia/101468Idowioad. 3. DeAngeli Net al. Cancer Chemother Pharmacol. 2022:89:515- a

527.4. Folp E etal. Cancer Chemother Pharmacol. 2022:89:499-514. 5. Viaseca At al. AUA 2024. Abstract POAE-C2 6, Jacob Jet al. AUA 2024. Abstraa P201. PeerView.com

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18. SunRISe-1: TAR-200 Monotherapy in
BCG-Unresponsive, HR NMIBC (Cohort 2)1*

CR Rate in Patients With HR NMIBC CIS FDA Breakthrough Therapy Designat
zw 828 86.2
a CC An)
go
&
= ©
g° en
§ » $
So z
Centrally Assessed Investigator %
(N= 58) ‘Assessed E
(N= 58) E
= 21 of 23 responses are ongoing
Landmark Time DOR ch a = 11 pts had a DOR of 26 mo
E (10 of 11 ongoing)
6 months 93% (61-99) 3 = 6 pts had a DOR of 212 mo (all ongoing)
None of the patients with CR have
12 months 84% (49-96) undergone radical cystectomy

Median folow-up in responders was 29.9 weeks (range, 14-140
TAR-200 was well tolerat low-grade 1 or 2 AE: E Sa
TAR-200-related SAEs, grade 23 AEs, and 7 oo ee ene we

dis nfrequent Time, mo

ontinuatio

1. ps elnicaral.govstucyNCTO4640629.2. Daneshmand Set al. AUA 2023, LBA 02-03. 3. Necch A et al. ESMO 2023. LBA10S. m
4. Jacob Jet al. AUA 2024. Abstract P201. PeerView.com

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19. Phase 3 SunRISe-3: BCG-Naive, High-Risk NMIBC*

Key Eligibility Criteria E Group A (n = 350)
+ Patients with histologically TAR-200 (gemcitabine 225 mg Q3W [induction phase]
12W tenance phi trelimab
confirmed high-tisk NMIBC and Q12W [maintenance phase]) + cetrelimal
(high-grade Ta, any T1, or CIS)? Group B (n = 350)
+ BCG-naive (no prior BCG, or BCG (QW for 6 wk [induction] and QW
last exposure >3 y prior to
randomization)
+ Age 218 y Group € (n = 350)
+ ECOG PS 0-2 | TAR-200 (gemcitabine 225 mg Q3W [induction phas

N= 1,050 ) and Q12W [maintenance phase])

-

Primary endpoint: EFS (time from randomization to first occurrence of HR disease, progression,”
or any-cause death, whichever occurs firste)

Secondary endpoints: Overall CR rate (CIS only)‘/duration of CR,° RFS, TTP, OS, cancer-specific survival,
safety and tolerability, patient-reported outcomes

JAH ib pp dense must ety reset (tue prior andren and docente tL once; lune cag a tering qu e nega canica o
high rade UC in patents win papila-ony isease. AI AES associated wth any rr surgery andlor inavesical therapy must have resoved to CTCAE v8.0 grade <2 pror andomizaon
* Progression defined as stage increase rom Ta to T1 or from CIS o Tt or progression to MIBC (T 22) or lymph node (N+) or distant (Ms) disease, whichever occurs fst.
jon of patients wih CIS who have no presence of HR disease at 6 mo.
st whichever occurs st. —
1. itps/cincalials.govistudy/NCTO5714202. PeerView.com

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20. Phase 3 SunRISe-5: Recurrent, HR NMIBC After BCG12

Group A (n= ~125)
TAR-200 m

Primary endpoint
+ Disease-free survival

ing a maintenance phase

Key secondary endpoints
+ Recurrence-free survival

Time to next intervention
Time to progression
Time to disease worsening
Overall survival
Safety and tolerability
PROs/HRQOL

Group B (n
Int

Intravesical mitom
Weekly during an induction
nthiy during a maintenance phase

Disease-free survival is defined as time from randomization to first recurrence of HR NMIBC (high grade Ta, any T1 or CIS),
progression, or any cause death, whichever occurs first

The study will evaluate whether TAR-200 will prolong disease-free survival when compared with intravesical chemotherapy in
Patients with papillary-only HR NMIBC recurrent after BCG therapy who refuse or are unfit for RC

1. Porten$ et al. AUA 2024. 2. ips-cinicariis govistudyINCTO6211764, PeerView.com

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21. SunRISe Trials Underway’

SunRiSe-1 [im TAR-200 + cetrelimab versus cetrelimab
alone in BCG-unresponsive NMIBC RER

for more on

SunRise-2 IN TAR-200 + cetrelimab versus concurrent therapeutic

A ; approaches to treat
chemoradiotherapy in MIBC Resear cancer

SunRise-3 jam TAR-200 + cetrelimab versus intravesical
BCG in BCG-naive, high-risk NMIBC
+ TAR-200 + cetrelimab as neoadjuvant

SunRiSe-4 therapy in MIBC

+ TAR-200 versus intravesical chemotherapy

SunRISe-5 in recurrent, high-risk NMIBC after BCG

1. its Iciicolials.gov. PeerView.com

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22. Intravesical ADC Approach: EV-1041

EV-104 (NCT05014139) is a phase 1, open-label, multicenter, dose-escalation and dose-expansion
study designed to evaluate the safety, tolerability, PK, and antitumor activity of intravesical
enfortumab vedotin in adults with NMIBC

Month 13 Month 412
Patient Population
+ Histologically confirmed =
BCG-unresponsive CIS; Induction laintenance
acs: Sen Intravesical EV cial
*| monthly Follow-up
+ Unfit for or “refuse” instillation x
radical cystectomy
+ ECOG PS <2
1. Kamat AM etal, ASCO GU 2023. Abstract TPS582. PeerView.com

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23. FGFR Mutations Are Frequently Observed
in Bladder Cancer!

>60% ~30% ~30% ~20%
1

Tumor invades.
= subepithelial ‘Tumor eases

ors can be effective across the disease spectrum )

1. Knowles MA et al. Nat Rev Cancer, 2015:18:25-41 PeerView.com

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24. TAR-210 Erdafitinib Intravesical Delivery
First-in-Human Phase 1 Trial!*

r
Molecular Eligibility shite TAR-210-D
FGFR alterations: 4 malay
+ Flexible molecular eligibility strategy ; TAR-2108

used) se -2 molday
~ alo conta sth - Rae mue
or PCR :
E IR NMIBC (Cohort3) Part 2: Dose Expansion
> FLE CHE > Recurnt history flowrgrade on + Expansion of both dose levels

N y) Visible target lesions Fi te Re ¡every 3 monte wah

= continued treatment for up to 1 year if recurrence

free (cohort 1) or complete response (cohort 3)

(lial cto date: Marc 22, 2028,
1.10 5, Yuan Y. R Stat Soe Sor C Appl Stat 2016;64:507-523.2. Yuan Y etal. Cin Cancer Ros. 2016:22:4291-4301 ñ
PeerView.com

3. Viaseca A at a. AUA 2024. Abstract PD48.02. 4. hips-Jciicatials gowstudyINCTOS316155.

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25. TAR-210 HR NMIBC (Cohort 1): Response Rate!

HR NMIBC With FGFR-Alterations (Cohort 1)
(N=21)

man 10 90% estimated 12-month RFS
Care rate? (n =21)

100
4 may (n= 11)
- Median RFS was not estimable

- 20f 21 patients have recurred

Patients

- Median duration of follow-up
8.9 months

No difference observed in RFS.

between the TAR-210 dose levels

TARADO 89 mon ange 38)

7 7 7 = 5 7 2

Treatment Duration, mo

+ Indicates patent was censored
Aa teatod patents wore eficacy evaluable. RFS was estimated using the Kaplan-Meier method. —,
1. Viaseca A etal, AUA 2024. PeerView.com

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26. TAR-210 IR NMIBC (Cohort 3): Response Rate!

IR NMIBC FGFR-Altered (Cohort 3)

(N = 43)
Overall, 31 patients were evaluable for
x ne response?
= Boy nen ponse
Tarzıod Y ete
M roc (= 22) 90% CR rate, with 28/31 patients
vane rre cn achieving a CR at week 12
a Overall, 100% of patients achieved
= À to Crta PD a clinical response; 3 patients had a
# Assessment non-CR/non-PD response
D> Treatment orgoing Consistent CR rate across both dose
Treinen 5
Tan are vet tm contain (24/28) of CRs are ongoing at time
T Treatment completed of clinical cutoff
Sty contas
77 Dr u Ste scorn
: : ae Felon peed

Durable Response Rate at
Specific Landmarks¢

Phase 3 MoonRISe-1 Underway?: TAR-210 vs IV 6 months 100 (100-100)

(95% Cl)

chemotherapy in IR NMIBC with susceptible FGFR alterations

9 months 89 (43-98)

+ Indicates patent was consorod

43 patonts were treat, 31 patients were effcacy evaluable for CR and DOR. * Efficacy evaluable patients wore those having atleast one disease evaluation or

‘discontinuing treatment prior to ther rt disease evaluation for either PD or recuence. © DOR was estimated using the Kapla Meier method. si

1. Vissoca A et al, AUA 2024 PeerView.com

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27. Summary of the Key Efficacy and Safety Outcomes of
Novel Therapies for the Treatment of HR NMIBC

Imarenion Comme CHE RO MARC Moda Fonumb Alam
One
crete mans 115 spare een Omega Cnecgant
a + hac via
rar
Our taras neo a en a im o
poses prose prose
suso consi Pmuezongns Gen FA on gos FARM a
pac ous) Se
saree oe Ne = nes) ner toos ce ne
DOR Tan =
abies e. oo run so. wn aS Pr
ann
rer
Kanne: gotea
ne meme ee ques RAE Stas sex gatas
sate 74 doter Me te me
cen 2% aeconraaon

1. Tyson MD et al, AUA 2024. Abstract P2-02. 2. LIR etal. J Cin Oncol. 2022:40(suppl 16) Abstract 4597. 3. Jacob etal. AUA 2024. Abstract P2.01. 4. Chamie K.
NEJM Evidence. 20222. 5. Boorjan SA et al, Lancet Oncol 2021:22:107-117. 6. Balar AV otal. Lancet Oncol. 2021 Jui22918:030. 7. Necch À et al. Lancet Oncol

2024:81470-2045:00178:5.8. Black PC etal. Eur Urol. 2023:84:596:544. PeerView.com

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28. Carol: A Patient With NMIBC

Panel Discussion

+ 61-year-old patient y : E

with HR NMIBC What options will Carol have for
+ ECOGPS1 therapy now and in the future?
+ BCG-unresponsive |
+ Undergoes repeat f: Practical points/tips on using

TURBT; no residual - Pembrolizumab?

tumor - Gene therapy?
+ Refuses RC - TAR-200, TAR-210 approaches?

+ AE management?
$ + Care team education/logistics?

+ When do you send for FGFR testing?
A What if this were intermediate-risk?

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29. Reshaping Treatment
Algorithms for MIBC

Matthew D. Galsky, MD

Professor of Medicine

Icahn School of Medicine at Mount Sinai

Director of Genitourinary Medical Oncology
Co-Leader, Cancer Clinical Investigation Program
Associate Director for Translational Research
Tisch Cancer Institute

New York, New York

2000-2024, PeerView

30. Bladder Preservation Approaches for MIBC‘?2

Phase 3 SunRISe-2: TAR-200 + PD-1 Inhibitor Cetrelimab vs Concurrent Chemoradiotherapy

a a
| „Key Eligibility Criteria | | | Cetrelimab + TAR-200
+ Patients with MIBC aR) Q3W (indwelling) for first 18 wk; then

À en Le | starting on week 24, Q12W through Assessments until
ing | study year 3 histologically proven presence

of MIBC, clinical evidence of
nodal or metastatic disease
(per RECIST v1.1), radical
cystectomy, death, or end of
study, whichever occurs first

Stratification®
+ Completeness (visibly
complete vs incomplete
[residual tumor <3])
+ Tumor stage (t0 vs
Ta/T1/Tis vs T2-T4a)

N=~550

Cisplatin 35 mg/m? QW x 6 wk or
gemcitabine 27 mg/m? Q2W x 6 wk
(investigator's choice) +
radiation therapy"

+ Primary endpoint: bladder-intact EFS

* Investgators choc of conventonal aioherapy over 65 weeks o:hypotaconated radiotherapy ove 4 weeks.» Based on screening re-TURBT. m
ups ina gevausyNETO4058802.2 Wars SB tal. ASCO 2021. stat 1PS4500 PeerView.com

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31. PeerView.com/GJT827

Harnessing IO for Trimodality Therapy in MIBC:
Phase 3 KEYNOTE-9921

Pembrolizumab + Chemoradiotherapy Versus Chemoradiotherapy Alone

Pembrolizumab Cystoscopy,

Pembrolizumab

FT 400 mg IV Q6W urine cytology,

ch a Cystoscopy, urine for -1 y biopsy as
(i274 NOMO) cytology, biopsy of indicated, and
CEE tumor bed, and imaging Q12W

dak) imaging 10 wk (#2 wk)

en Placebo IV Q6W + (42 wk) after CRT Placebo IV through year 2
nn CRT Say Q24W (+ 2 wk)

= 318 beyond 2 y

+ Stratification

- ECOG PS (0 or 1 vs 2)

— PD-L1 CPS (<10 vs 210)

- T stage (T2 vs T 3/4)

- Geographic region (US vs Europe vs ROW)
+ Primary endpoint: bladder-intact EFS

4. Tissot G ota. Eur Urol Focus. 2023:9:227-228. PeerView.com

Copyright © 2000-2024, PeerView

32. TURBT + Chemo-Immunotherapy Alone for MIBC1-3

HCRN GU16-257 key Eligibility Criteria
+ MIBC
+ cT2-4aN0MO
N=76

eee |

Gemicis + nivolumab x 4 cycl 5 5
Fr FENTE 23
Clinical restaging: cystoscopy + biopsies, urine cytology, MRI } 3-2
n=72 25
go
gs
2s
ö
0 2 4 6 8 1012 14 16 18.20 22 24 26 28 30 32 34 3638404244
Time From Registration, mo
ystectomy free
Co-primary endpoints: cCR rate and performance of Im Local recurrence
CCR in predicting treatment benefit (ie, 2-y MFS if no 12 Cystectomy
cystectomy and pCR in immediate cystectomy) 1m Metastatic recurrence
* Treatment basod on patents choice ee N
1. Galsky MO et al. ASCO 2021. Abstract 4503. 2. Galsky MO et al. ASCO GU 2023. Abstract 447.3. Galsky MD et al. Nat Med 2023.29:2825-2894, PeerView.com

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33. Clinical CR Predicted Treatment Benefit!

NFS (Landmark Analysis) OS (Landmark Analysis)
0
de CCR predicted
E dé treatment benefit
7 with a positive
E predictive value
a à
3 Log-rank P = 007 Log-rank P=.003 of 0.96
Sol o 9
o 10 E E pi o 10 E E] o (95% Cl, 0.89-1.0)
‘Time From Clinical Restaging, mo Time From Clinical Restaging, mo
one a = w oo a 2 “ o
Dee E # 5 en à E 2 y o
These findings may help advance a more personalized approach to the management of
MIBC leveraging clinical response-based risk stratification
1. Galsky MD et al. ASCO GU 2023. Abstract 447. 2 Galsky MD et a. Nat Med. 2023:20:2825-2894, PeerView.com

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34. Several Ongoing Phase 3 Trials With
Perioperative Immunotherapy

Cisplatin Eligible Cisplatin-Eligible Trials
CA017-078'

Neoadjuvant phase Adjuvant phase

+ Gem/cis + nivolumab
10 + chemo 10 + Fully accrued N = 861

or or NIAGARA?

10 + novel agent 10 + novel agent
= > * Gem/cis + durvalumab

+ Fully accrued N = 1,063

KEYNOTE-866°
Radical cystectomy and + Pembrolizumab + EV

+ Gem/cis + pembrolizumab
907
pelvic lymph node dissection Enrollment ongoing, estimated N = 784

1. Mips/cicatils govstudyiNCT03661320, 2. htpsitnicatials govlstudyINCTO3732677. —
5. ps Iinicalrats goustudyNCTO3924856, 4. hps:/Icnicatrals. gov/sUSy/NCTO4700124. PeerView.com

Placebo + chemo

+ Fully accrued

KEYNOTE-B15/EV-304*

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35. Several Ongoing Phase 3 Trials With
Perioperative Immunotherapy

Cisplatin Ineligible Cisplatin-Ineligible Trials

Neoadjuvant phase Adjuvant phase KEYNOTE-905/EV-3031
+ Pembrolizumab + EV
+ Enrollment ongoing, estimated N = 857
VOLGA?3

+ Durvalumab + tremelimumab + EV
+ Enrollment ongoing, estimated N = 830

SunRISe-445 (phase 2)

+ TAR-200 + cetrelimab
+ Enrollment ongoing, estimated N = 160

10+ 10+
novel agent novel agent

Observation

Radical cystectomy and
pelvic lymph node dissection

1. tps ur cincatals. govstuoyNCTO3924805. 2. Ms: incas gov/studyINCTO4960709. 3. Pontes T ota ASCO GU 2022. Abstract TPSS79, À
4. mis Iinicalrials govistudyINCTO4918512. 5. Psutka SP et al, ASCO GU 2023. Abstract TPSSEA. PeerView.com

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36. Chemo Versus Chemo + IO in Lymph-Node-Only mUC*

+ LN-only mUC falls in between neoadjuvant and metastatic, and optimal treatment
of such patients has never been well defined

CheckMate -901? CR

CCE
ORR (95% C1)
Altrandomized patients ORR 5% CD Lu ony patients Patents with CR, n 19

Median time to CR (range). mo 2101822) 20(1633)
57.6 7 Median duration of CR (95% Cl), mo NR(220-NE) 87 (6.7-15.6)
x (618-632) a
$ y 12:m0 CR rate (95% Cl), % 70(51-82) 32(10-57)
4 24-mo CR rate (95% Cl), % 65 (45-79) NA (0)
= Ongoing CR after treatment, n (%) 14 (41) 3(16)
ET ‘Median OS (95% Cl), mo 46.3 (24.0-NE) 24.9 (214-299)
ms 37
te 7 55 HR = 0.58 (034-100)
NIVO + GC sc NIVO + GC sc Median PFS (95% Cl), mo 30.5(9.6-NE) 8.8 (7.5-10.9)
(n= 304) (n= 304) (n= 54) (n= 56)
. . HR = 0.38 (022.066)
+ CR rates for NIVO-GC treated patients with LN-only L J
were ~2x that of GC-treated patients
FOR pera 7
1. Galsky MD et al. ASCO 2024. Abstract 4509, PeerView.com

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37. Adjuvant MIBC Trials With PD-L1/PD-1 Inhibitors

CheckMate -2742 AMBASSADOR?

o =

o =
=
+ Coprimary endpoints:

1 1
' H
' 1
1 1
H ;
' H
5 1
| ;
1 1
1 | | 1
+ Primaryendpoint: DFS | * Primaryendpoint:DFS | DFS and OS
H ;
' '
1 5
' H
; 1
1 1
| i
' :
1 1
H H
1 :

+ Key secondaı » Key secondary .
cn dpolrte: 08 DSS, endpoints: OS, sogen DES
distant MFS, NUTRFS NUTRFS, DSS. > Bee.

2 in PD-L1-positive and

PD-L1-negative patients
Did not meet DFS Met DFS Met DFS
primary endp« primary endpoint primary endpoint

1. ps cnicalials.gouistudy/NCTO2450351. 2. Mtpscinicaials govistudyINCTO2632409. 3. ips:cinicaltils govistudyINCTOS244384, PeerView.com

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38. CheckMate -274: Continued DFS Benefit Was Observed With
Nivolumab Versus Placebo in Both Populations’

10 MT PR PD-L121%
a Modan DFS 5% CD. mo
” Median OFS 98% CD. mo Wo TENE
pa wo BOS) p Peo Basen)
Po ee wR oseest 4087072
7 HR= 07 OC. 038080) 7

0% som

we a hs à Nivolumab
gs Nivolumab ge i

40 i + H

0 od so i Ea

20: H H Placebo 20- } H

so pod 1 E:

ot : i o : i

DER Amann 0 0 6 2 de 2% do % a2 de ss © 0
cama Time, mo FRE na es
moss mm mm mm Bw 8 4 0 mow 2 Bm nu & Es» 2 0
EE te ia eo om A mow un 8 2 6 OMB 1 9 2

¢ mDFS doubled with nivolumab vs placebo ( mDFS was >6x longer with nivolumab vs placebo )

+ Median folow-up of 36.1 months: minimum folow-up of 31.6 months ™
4. Galsky MD et a. ASCO GU 2023, Abstract LBAA4®. PeerView.com

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39. CheckMate -274: Interim OS Data Favored
Nivolumab Versus Placebo in Both Populations’

ITT PD-L1 21%
100:
90:
so
mo:
©.
x
gs
40
20: H
TIVO 6955 (58.1-NE) H TIVO NRINE)
20 P8O SO1(S82NE) 20 H PRO _NR(@BO-NE)
HR (95% Ch, 0.76 (081-096) H | HR 95% ch, 056 (036.086)
10 H 40. i :
— —r + - + 0 r + + -
0 6 12 18 24 30 36 42 48 54 60 66 72 78 0 6 12 18 2% 30 36 42 48 54 Go
No. at Risk o No. at Risk Tine.
NIVO 353 325 208 268 244 220 188 150 123 92 60 33 4 0 NIVO14D #7 HS 93 73 82 41 Z% HN 1 0
PRO 356 308 261 254 226 194 167 136 109 79 56 32 10 0 Peo 142 116 106 67 65 46 36 26 12 2 0
+ 0S otowp is ongoing as e respects stata! Boundary fr scarce was not mat at ne me of nes Modan (minimum) flop in he TT.
opio, 361 O1’) amis di rama) elo n POL 21% Polo, 234 (11) mie OS was Gold as tm om at ol randorkzaen cts of
eat (rom any cause) m
1. Galsky MD et al. EAU 2024. PeerView.com

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40. AMBASSADOR: Pembrolizumab Demonstrated
DFS Benefit at Interim Analysis!

DFS (ITT Population) Overall Survival
Evonts/Total,n_ Median (95% Cl), mo
Eveots/Total,n Median (85% Ci), mo Pembrolizumab 1311354 509 (43.6-NR)
E Pembrolizumab 1471358 29.0 (21.8-NR) — 129048 un
il ee ir pen . HR = 0.98 (95% Cl, 0.76-1.26), P<.884
» HR = 0.69 (95% 01.054.087); P= 001 . Pembrolizumab
ze >
ge Pembrolizumab à * oe
E. g-
| Median folow.up (rango) “¿| Median folow-up (range)
“| 223 months (0.03-48.9) *| 369 months (35.9-37.9)
Time, mo Timo, mo
1. Apolo AB e a ASCO GU 2024. LBASST PeerView.com

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41. Potential for Improving Daily Management:
Subcutaneous 10

+ SC administration provides an

Phase 3 Studies Assessing SC IO Across Tumor Types
alternative with potential benefits for
both patients and providers
+ SC dosing may
— Alleviate the need for IV
vein ports
— Allow more patient flexibility
— Reduce dose preparation and

IMscin00112
SC atezolizumab in NSCLC
January 2024: Approved in the EU for all indications?

CheckMate -67T*5

SC nivolumab in RCC
administration times

- Optimize occupancy in infusion
centers

May 2024: Under FDA review for all indications*

CREST’
Cohort B: SC sasanlimab in NMIBC
See the Practice Aid for more
on therapeutic approaches
to treat bladder cancer

RELATIVITY-127°
SC nivolumab + relatlimab in metastatic melanoma

otto M et al. Ann Oncol, 2023:34:899-702, 2. tp clinical govistudyINCTO3735121. 3 its irstwordpharma. comstry/5818570.
tps Icinicalils govistudyINCTO48 10078. 5. George $ otal. ASCO GU 2024. Abstract LBA360. 6. MIS now bms.comnewsicorporae-fnancal2024 Bristol
tty Su Amours Ut Acton

Date-by-the-U.S.-Food-and-Drug-Adminitration-or Subcutaneous-Nivolumab-nivlumab-and-hyaluronidaseldefaut aspx yy
can govsyNCTOS16S7- 8 pe Cc Don NCTOEEZE 38, PeerView.com
PeerView.com/GJT827

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42. CheckMate -67T: Nivolumab SC Provides Clinical
Equipoise to Standard IV Dosing!-?

+ Eligibility: Patients with advanced RCC/mRCC with clear cell component who had
progressed during or after receiving <2 prior systemic regimens
+ Co-primary endpoints met: PK noninferiority between NIVO SC and IV

NIVO SC NIVO IV
1,200 mg + rHuPH20 Q4W 3 mg/kg Q2W
(n = 247) (n = 245)
Doses received, n 8.6 17.7
‚Administration time, min 47 30.9
Patients with 21 dose delayed, n (%) 89 (36.0) 134 (54.7)
Patients with 21 infusion/injection interrupted, n (%) 1 (0.4) 10 (4.1)

Average administration time with nivolumab SC was <5 minutes = Ash
Similar ORR, DCR, and DOR observed in SC vs IV biens
Important for patients receiving single-agent checkpoint blockade pie ES CEN
Treatment implications in the perioperative setting

1. George S et al. ASCO GU 2024. LBA 360.2. George S et a. ASCO 2024, Abstract 4535. 3. Bouron MT etal, ASCO 2024. Abstract 4532 PeerView.com

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43. irAEs With Immune Checkpoint Inhibitors
Can Affect Any Organ

Dermatologic Endocrine Gastrointestinal Pulmonary
Rash Hypothyroidism Diarrhea Pneumonitis
Pruritus Nausea
Vomiting
Hepatitis

See the Practice Aid for more on approaches to

adverse event management in bladder cancer

PeerView.com

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44. Immune-Related Adverse Events
Can Occur at Any Time‘?

Communicate
With Patients

Colitis Pneumonitis Potential onset of
3 symptoms
ö What to watch for
5 Duration they may
% [skin Endborinapathy experience the irAE
© |toxicity, P: E
rash, or atients may be more
pruritus likely to adhere to treatment
Nephritis when they have a full
picture of irAEs
0 4 6 8 1 12 14 330
Duration of Treatment, wk
1. Marin Fetal. Not Rov Cin Oncol 2018:16:563. 2. NCCN Cinca Practice Guidelines in Oncology. Management of Immunotherapy Related Toss. Version py
1.2024. Ns Jin ncen oriprofessionas/physician_glipatimmunothorapy pal PeerView.com

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45. PeerView.com/GJT827

Charles: A Patient With MIBC

56-year-old athlete,
excellent health
Cystoscopy and imaging
consistent with a sessile mass
at the anterior bladder wall
Diagnosis of clinically
localized MIBC

Good renal function
Treated with 4 cycles of
gemcitabine plus cisplatin
followed by RC/neobladder
Pathology: ypT2N1

PD-L1: CPS20%

Panel Discussion

Would adjuvant IO be appropriate?

What are important patient discussion
points if/when initiating adjuvant immune
checkpoint inhibitor therapy?

What AEs do you and your team look out
for and when should patients call in?
Potential future setting for a subcutaneous
10 approach?

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Copyright © 2000-2024, Peerview

46. Refining Frontline Therapeutic
Options in mUC

Michiel S. van der Heijden, MD, PhD

Medical Oncologist and Research Group Leader
Netherlands Cancer Institute

Amsterdam, The Netherlands

2000-2024, PeerView

47. Advancing Treatment Options in the
1L mUC Setting via Combination Approaches

Platinu

ased Chemotherapy + Immune Checkpoint Inhi

+ No improvement in survival
- Investigator’s choice chemotherapy + atezolizumab (phase 3 IMvigor130)'
- Investigator’s choice chemotherapy + pembrolizumab (phase 3 KEYNOTE-361)?

+ Improved survival FDA Approved
- Gemícis + nivolumab (phase 3 CheckMate -901)%* March 2024

DC + Immune Checkpoint In!

ion

+ Improved survival FDA Approved
- Enfortumab vedotin + pembrolizumab (phase 3 EV-302)$5 December 2023

1. Gasky MD et al Lancet. 2020.395:1547-1587. 2. Pons Total Lancot Oncol 202122931-945.. van der Heiden MS e al. N Engl J Mad. 2023:389:-1778-1789.

4 tps han da gong osouros-nlormaton-aproved-drsiéa-aproves-awolumatcombinaton-esplabman-gometabineunosotat-o-metastat-

‘whet 5. Poules Tet al N Engl Med. 2026;390:875 886.6, tps ww da govldeugsresources-nformaton-approved-drgs/Ga-opproves-enforumab-vedoin- ñ
‘ifv-pembrolizumab-tocally-advanced-or-metastatic-vrothelial-cancer. PeerView.com

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48. Is Cisplatin (Versus Carboplatin) a Better Partner for
Immune Checkpoint Inhibition?

IMvigor13012 KEYNOTE-3615
Investigator's
cee Gi ArmA ArmC Ser
ec, Patients,n mPFS,mo mPFS,mo HR (95% Cl) alien, es HR (95% Cl)
(n=451) (n= 400) Fs
Cisplatin 273 8.8 6.4 0.73 (0.55-0.97) 207/312 0.67 (0.51-0.89)
Carboplatin 578 7A 63 0.84(0.70-1.02) 286/391 0.86 (0.68-1.09)

1. Galsky MO et a. Lancet. 2020:395:1547-1587, 2. Galsky MO et a. Col Rop Med. 2024:5:101393

3. Pones Total, Lancot Oncol 2021:22:931-946 PeerView.com

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Copyright

49. Phase 3 CheckMate -901: Nivolumab + Gem/Cis
Versus Gem/Cis in Cisplatin-Eligible Patients1-32

Combination phase Monotherapy phase

NIVO 360 mg on d 1+ NIVO 480 mg Q4W

Key Eligibility Criteria 0 mg/m? on d 14 (until progression,

ee 2.000" D
i + Tumor PD-L1 11 2 y :

unresectable ee
or mUC involving the +» ¿PSSS —Q

renal pelvis, ureter, (Sa) Sr
De un + Liver metastases em

+ Cisplatin eligible uam) Cis 70 mg
+ ECOG PS 0-1

up to 24 mo)

up t

+ Primary endpoints: OS, PFS per BICR
+ Key secondary endpoints: OS and PFS by PD-L1 2 1%, HRQOL
+ Key exploratory endpoints: ORR per BICR, safety
+ Modan (ange) stoy fotowup, 336 (7462.4) mo. Patents who continued ci coud be sched 1 gon fr he remainder of he platinum doublet yes
{Upton wa. A maximum o 24 mo rom fr dose of NV administered as pat of te NIVO + gemves combinan.

‘hostels Joist INCTODOJO008 2. van der Heiden MS ta, ESMO 2029. Abstract LBAT ASE
3. van der Heiden MS et al. N Engl J Med. 2023:389.1778-1789. PeerView.com

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50. PeerView.com/GJT827

CheckMate -901: Nivolumab + Gem/Cis
Improved OS (Primary Endpoint)!.2.2

100 mos NIVO + gemicis
pe Treatment Events/Patients (95% CI), mob is the first 1L
12-mo rate: NIVO + gemvcis 1721304 21.7 (18.6-26.4) current immune

70.2% Gemicis 199/304 18.9 (14.7-22.4) checkpoint inhibitor
HR = 0.78 (95% Cl, 0.63-0.96) + chemotherapy

m 60 24-mo rate: P=.0171 combination to
Eso 46.9% improve OS
8 40 in this setting

30
NIVO + gemicis
20
10 Gemícis
FDA Approved for 1L
6 12 18 24 30 36 42 48 54 60 66 Treatment of
Time, mo Unresectable or mUC?

+ Mean (ange) stay folow-up, 3. (74-624) mo.» OS was stimated in al randomized paints and donadas timo from randomization to death tom any cause.
For patents wihout documented death, OS was censored on the lst date te patent was known o be ave. For randomized pabents wih no loup. OS was

censores at randomization. «OS final analysis stasteal boundaries: Povalue boundary = 0311: cal HR = 0.7960

1. van der Heiden MS eta. ESMO 2023, Abstract LBAT. 2. van er Heiden MS eL al. N Engl J Med. 2023:389-1778-1789 3. hips www Ida govldnygsiresources- isa
information approved-drugs/da-approves-nivolumat-combinaton-CSplati-and-gemciabine-unresectable-or-metastati-urotoal, PeerView.com

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51. Phase 3 CheckMate -901: Nivolumab + Gem/Cis Improved
PFS (Primary Endpoint)1:22

100: mPFS
90 ‘Treatment Events/Patients (95% Cl), mobs
NIVO + gemicis 2111304 797595) atistically significant and
a Gemicis 191/304 7.6 (6.1-7.8) nically meaningful
70 HR = 0.72 (05% CI, 0.59-0.88) improvements in PFS vs
we 60 P= 0012 gem/cis alone as 1L treatment
2 6 for unresectable or mUC
4 12-mo rate:
£ 40

NIVO + gemicis

19.6% Gem/cis

o 6 12 18 24 30 36 2 48 54 60
Time, mo

+ Malan (ange) suc folow-up, 3. (74-624) mo» PES was estimated in al randomied patients and defined as time from randomizaion to fest documented
ese progression (per BICR assessment using RECIST v1) or death due to any cause, whichever occured fra Patients who not progress orde were

‘onsored ast evaluable tumor assossment. Paints without on-study tumor assessments who dd ot de were Censored at randomizaton. Patents who sated any

‘Subsequent anicancar horapy wihout pro: poros progression were consored a! at ovalabl tumor assessment ele ‚lan o subsequent narapy

FS final analysis statistical boundaries: P-value boundary = 01. cal HR = 0.7738 ei

1. van der Heiden MS etal. ESMO 2023. Abstract LBAT. 2. van der Heiden MS et al. N Engl J Med. 2023:389:1778-1789. PeerView.com

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52. Phase 3 CheckMate -901: Nivolumab + Gem/Cis
Is Associated With Deep and Durable Responses!»

ORR (95% Cl) and BOR per BICR®

TTR and DOR

CR + is is
70 we = IE Any Objective response: NVO*Gemicis Gomicis
60 (51.8-63.2)
aa MTTR (Q1-Q3), mo 2.1 (2.0-2.3) 2.1 (2.0-2.2)
8 50 21.7 (37.5-48.9) mDOR (95% Cl), mo 9.5 (7.6-15.1) 7.3 (5.7-8.9)
¿so = NIVO+GemiCis Gomicis

(n=66) (n=36)
MTTCR (01-03), mo 21(1922) 21(1922)

35.9 313
10 i mDOCR (95% CI), mo 37.1(18.1-NE) 13.2 (7.3-18.4)
0
$0,% 253 283 + ORR and CR rates were notably higher with
NIVO + gemícis and associated with deep and
PD, % 95 128 durable response:
UE, % 76 158 The CR rate nearly doubled with NIVO + gem/cis

- DOCR was almost 3 times longer with NIVO + gem/ci
NINO + GeniCle Denis de: maximum of 2 y of NIVO treatment
(n = 304) (n= 304)

in randomized patents.» The most common reasons for UE response included death before fest tumor assessment. withdrawal of consent. treatment stopped due
Lo ton, patent never teated, and cap of subsequent anticancer therapy Dior st tumor assessment Based on patents wih an ojschve response per BICR
(PR or CR as BOR) * Based on patents wih a CR per BICR.

‘van dor Hojden MS et al ESMO 2023 Abstract LBA. 2. van dor Heiden MS ot al. N Engl J Med 2023:389:1778-178.

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53. Treatment:
Any
Leading to discontinuation

elated AE,

Phase 3 CheckMate -901:
TRAEs in All Treated Patients?

Gem/Cis (n = 288)

Anemia
Nausea

Newvopenia

Decreased neutrophil count
Fatigue

Decreased appetite

Decreased patoet count
Decreased white blood cell count
Vemiing

Asthonia

Thrombocytopenia

Pruntus

Constipation

Rash

Diarrhea

Hypothyroidism

Increased blood creatinine
‘Leukopenia

+ Includes events tha occured in treated patents between fest dose and 30 d after ast dose of study therapy. Tomado plot displays individual TRAES
‘occuring at any grade in 210% of rated pation in either arm.» One grade 5 event occured in each arm (sepsis In the NIVO + gemicis arm and acute

Key injury in ine gems am)

Any Grade Any Grade Gradi
97 93 52
21 17 8
” “
”
| Grade 4-2
LES
=
o ny 2 2 “ &

°
Incidence, %

1. van der Holden MS et al. ESMO 2023. Abstract LBAT. 2. van der Heiden MS et al. N Engl Mod. 2025:389:1778-1789.

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54. Phase 3 EV-302/KEYNOTE-A39: Pembrolizumab + EV
Versus Platinum + Gemcitabine in Advanced UC‘:

Key Eligibility Criteria 4 EV + pembrolizumab®
D RME UES Ech Stratification Orne PR Treatment until
locally advanced or = disease progression
+ Cisplatin eligibility pembrolizume
muc (ligblefinelilble) 11 per BICR, clinical
+ Eligible for platinum, (slabetine| ae progression,
EV, and P PI aa an sb unacceptable
low) toxicity, or
+ PD-L1 inhibitor naive ty,
+ Li Chi tl N ic
+ GFR230 ml/min ca teo! menu san Ecos
+ ECOG PS <2 (EE gemcitabine
N=886 \ 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

+ Stastcl plan for analysis: the fst planned analysis was pecormed ater approximately 526 PFS (nal) and 356 OS events (ner): OS was postive at intern
{he OS intorm analysis was considered nal. Data cult: August 8, 2023; FP Api 7, 2020; LP: November 9, 2022.» Cisplan ehgbäty and assignmandosing of

Esla v coca wre rocas: ants ech nk je 1 EV 12599 Von days 1 an Band pmbekzuma 200 mg Von dy 1

“Maintenance therapy could bo used folowing completon andlor isconunuaton of platnum-contanng therapy AN

1 Pons Tet aN Eng Mad 2024:200 079.08. PeerView.com

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55. Improved OS With Enfortumab Vedotin + Pembrolizumab’

Events) gy Two-Sided P mOS (95% C), mo

100

so EV+P 442 1930301) | 047 (25.4-NR)
<.00001

80 Chemo 444 226(5097 [(0:36-058) 164 (139-183)

70
Risk of death we

50, 53% in patients who received

50 EV + pembrolizumab

40
30
20
10

OS, %

Full FDA Approval

+ for 1L Treatment

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 2
of mUC’

No. at Risk Time, mo

EV+P 442 426 409 304 76 331 270 222 182 141 108 67 96 22 12 8 1 1 1 —

Chemo 444 423 393 358 317 283 209 164 125 90 60 37 25 18 2 7 6 2 1 —

+ Data cut August 8, 2023 FP: Apr 7, 2020; LP: November 9, 2022, Madan survival olow-up: 17.2 mo. OS at 12 nd 18 mo was estimated using Kaplan-Meier

‘method. *Coledated using stated Cox proportonal hazards model. HR <1 favors tho EV + pembolzumab am.

{Poms Tot al N Engl J Med 202:300:875-888, 2. tps: nwo da govidrugurescurces formation approved-drgséa-approves-enortumab-vesotn-f- —
Pembroizumab-Iocaly-advanced-ormetastabc-rolhelalcancer PeerView.com

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56. Improved PFS With Enfortumab Vedotin + Pembrolizumab1

100
90
80

mPFS (95% CI)
mo

N Events(%) HR?(95% Cl) Two-Sided P

EV+P 442 223(50.5)

045(0.38-0.54) — <.00001

Chemo 444 307 (69.1)

PFS, %
88333

EV + pembro

30
20
in patients
10
a Chemo — received E
jembrolizumab
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 penbeolzumee
Time, mo
No, at Rsk
EVeP 442 409 261 33 29 26 107 12 102 7 45 % 17 6 3 1 —
Chemo 444 m 297 29 m 78 OS 41 M M 6 6 S$ + 2 1 1

Data cutft August 8, 2023; FP: Ap 7, 2020; LPI: November 9, 2022. PFS at 12 and 18 months as estimated using Kaplan-Meier method. Caleuated using
“stated Cox proportional hazards model: HR <i favors the EV + pembrolzumab arm.

1. Powes T et al. N Engl J Med 2024;300:875-888. PeerView.com

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57. EV-302 OS Subgroup Analysis:
Cisplatin Eligibility and PD-L1 Expression’?

05,%
csussscassi

SITIO NAAA
no mat Timo, mo

rr ee
ne me Time, mo
Go 210 109 14 160 9 116 0 anes os att

= PD-L1 High (CPS 210) = PD-L Low (CPS <10)

2 2
a6 ans #5
ge ge ever
8: wer so

= H Chemo 5

2 H ever a

| ne = 049 95% CL 0370.08) À] mes 0.46 95% ch 031-061) zu
toros ne cane Tine, mo

AER AER m HSI Ho eis I OO asa
Data cut August 8, 2023.
* Calculated using stratified Cox proporional hazards model; a hazard ato <1 favors the EV + P arm.

1. van dor Heiden MS etal ASCO GU 2024. LBAS30. 2. Bed J etal ASCO 2024. Abstract 4562. 3. van der Holden MS ot al ASCO 2024. Abstract 4563.

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58. EV-302 OS Subgroup Analysis:
Liver Metastases and Metastatic Disease Site!

osueesszess

a a zu 221 un Ut 0

08,%

03,%
Ê osusssazasi

so. Time, mo
5 Dr os ra
Data util August 8,2023
Calcite ug stated Cox proportional hazards mode; ahazar ati <1 favors the EV + Pam. >
1. van der Heiden MS et al. ASCO GU 2024. LBAS30. PeerView.com

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59. Phase 3 EV-302: Improved Overall Response?»

Significant Improvement in ORR Was EV+P | Chemotherapy
Observed With EV + Pembrolizumab (n = 437) (n= 441)
e PR © © Confirmed ORR, n(%) 296 (67.7) 196 (44.4)
= E crm m 95%Cl 63.1-72.1 39.7-49.2
© ds 2-sided P <.00001
æ © 387 BOR?, n (%)
go
g CR 127 (29.1) 55 (12.5)
» PR 169 (38.7) 141 (32.0)
F sp 82 (18.8) 149 (33.8)
EV+P ‘Chemotherapy PD 38 (8.7) 60 (13.6)
mDOR (95% Cl) NR (20.2-NR) 7.0 (6.2-10.2) NE/NA° 21 (4.8) 36 (8.2)

Data cut August 8, 2023? BOR according to RECIST v1.1 per BICR CR or PR was confirmed wih repeat scans 228 ar Ina response.
“Patents na other post basoine assessment and the BOR was deteminad 1 bo nt evaluable por RECIST V1.1 or no response assessment post baselno. N
1. Powis T et al. N Engl J Med. 2024:300:875-888, PeerView.com

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60. Phase 3 EV-302: TRAEs"?

EV +P (n=440) Chemo (n = 433)

Overan ] 97.0
Peripheral Sensory Neuropathy
Pruntus
‘Alopecia
Maculopapular Rash
Fatgue
Diamhea
Decreased Appetite
Nausea
Anemia
Neuropenia | Ev+P m CRT
‘Thrombocytopenia AN . 34 0:
100 90 80 70 60 50 40 30 20 10 O 10 20 30 40 60 60 70 60 90 100
Incidence, %

Grade 23 events were 56% in EV + P and 70°

Data cut August 8, 2025. TRAES shown in fgur ao any grade by prefered tom in 220% o patents for any grade in ir am. N
4. Ponies Tot a ESMO 2023, Abstract LAS PeerView.com

us

in chemotherapy arms

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61. EV-302 Patient-Reported Outcomes’

Change

EORTC OLQ-C30 Functioning Domains

Ev+P-

Ev+P Chemotherapy ‘Chemotherapy

LS Moan (SE) LS Mean (SE)

Functioning Domain

Role functioning 53612) -949(120) He 4047067) 004
Physical uncioning 2800) 250m) Pe 302(154005.70) 007
Social functioning 22) 5520120) HD 2srouwsz) os
Global heath status QOL -0.59(099) -312(1.01) Ia 254(04110467) — 0197
Cognitive functioning 0508) 2690087) Le 2150106420) 0400
Emotional funcioning 385(097) 196(098) be 189 (0190307) 0750

O —

a + à 5 0

—
Favors chemotherapy Favors EV +P

+ Patients in the EV + P arm demonstrated improved functioning across all functioning domains
compared to patients in the CT arm, based on change from BL during the first 26 weeks

1. Gupta Set al. ASCO 2024. Abstract 4502. PeerView.com

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62. Guideline Updates on 1L Therapy in
Advanced Urothelial Carcinoma

ESMO Clinical Practice Guideline’

Treatmentnaive advanced or
meiasiate UC (stage IV)

Treatment-naive advanced or metastate UC (stage IV)
"non EV + P unavailable or contrandicates

——@_ [+
— =

‘only
+ +

Cisplatin
eligible

Cisplatin
ineligible

1.Pondes Total. Ann Oncol, 2024;$0823-7534:00075-9. 2. ps: con orgproessional/physician_gk/pdbladder pal.

PeerView.com/GJT827

NCCN Guidelines?

AL Systemic Therapy for Locally Advanced or Metastatic Disease
(Stage IV)

Preferred regimens,

+ Pembrolizumab and enfortumab vedotin-ejív (category 1)

Other recommended regimens

+ Gemcitabine and cisplatin (category 1) folowed by
avelumab maintenance therapy (category 1)

+ Nivolumab, gemcitabine, and cisplatin (category 1)
followed by nivolumab maintenance therapy (category 1)

Useful under certain circumstances

+ DDMVAC with growth factor support (category 1)
followed by avelumab maintenance therapy (category 1)

Proferred regim
+ Pembrolizumab and enfortumab vedotn-etv (category 1)
Other recommended regimens

+ Gematabine and carboplatin folowed by avelumab
maintenance therapy (category 1)

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63. PeerView.com/GJT827

Diana: A Patient With mUC

71-year-old patient
Urine cytology and TURBT:
urothelial carcinoma
CT CAP: retroperitoneal LNs
ECOG PS 1

CrCl 60 mL/min

Current smoker

No autoimmune disease;
not on steroids

No FGFR alterations

Panel Discussion

What 1L options would you discuss
with Diana?

How do you educate her on expectations
for dosing/scheduling?

How does your care team handle AE
management?

How do comorbidities play into treatment
selection?

What if she had a HbA1C 9%?

Other important discussion points?

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64. Treatment Opportunities for
Progressive mUC

Shilpa Gupta, MD
Clinical Professor of Medicine

Cleveland Clinic Lerner College of Medicine of CWRU
Director, Genitourinary Oncology

Cleveland Clinic Taussig Cancer Institute
Cleveland, Ohio

2000-2024, PeerView

65. Treatment Paradigm for la/mUC Pre-ESMO 2023

Cisplatin-eligible

patients

Cisplatin-

ineligible
patients

Platinum-
ineligible
patients (10%)

PeerView.com/GJT827

Cisplatin-based
chemotherapy
LO

Carbo-Gem

EV-Pembro

Pembrolizumab

PD

Pembrolizumab
(level 1)
Avelumab/nivolumab

EV (level 1)

Sacituzumab
govitecan
Erdafitinib

Avelumab maintenance (FGFR2/3 alt)

PD EV (select patients)

PeerView.com

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66. Current Treatment Paradigm for la/mUC

la/mUC patients

Platinum-
ineligible
patients (10%)

No grade 2 PN; HbAte <8; C1C1>30.

PeerView.com/GJT827

Gem: + in
cis-eligible patients if
EV-Pembro
not available

EV-Pembro
(preferred)

um followed by
avelumab

Pembrolizumab

EV-Pembro
(select, fitter

patients)*

PD

EV

PD (select
patients)

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67. EV-301: Enfortumab Vedotin in 2L mUC122

Enfortumab
Vedotin

Target: Nectin-4, a type 1
transmembrane cell adhesion
molecule overexpressed in
epithelial cancers

Linker: protease cleavable

19 Events mOS,mo (95%
© Enorme vedotin 190901 12.68 (1050-1521)
1 Cmnotenps 167207 4978051070)

42 HR = 070 (8% cL. 086080)

5 Set

oe Enfortumab vedotin
2

BEEEEZEZESTETTELITIZIIIEIT)
Duration ot 5,me

Enoremab dot 201 206 22 257 246 ZU 22 10 1 HHS 6) $2 2 DDT

pause
ee PR ee Es A IE SUR EUR
13
Payload: MMAE = Events mPFS.mo (95% CD
= » Enfonumab vedoin 201001 555532582)
2020: FDA approved a Chemotherapy 231790737 (352.98)
je a 082,694 0081070)
ORR higher with EV vs chemo: ko BEER
41% vs 18%; P < .001 ba Enfortumab vedotin
24-mo outcomes support 0 ‘Chemotherapy
initial results “STITT TET eT THU wm
gra Duration of PFS, mo
* Data auto Ju 15,2020. EEE

1. Poules T tal N Engl J Med 2021;384:1125-1135. 2. Padcev (enfotumab vedotin)Proscrbing Information.

tos ww accessdata fa govidrugsatida_docsabel2023/761137s0191 pd. 3. Rosenberg Jet al. ASCO 2022. Abstract 4516, PeerView.com

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68. EV-301 Long-Term Outcomes’

os PFS

Event, NN __ Median (95% Cl aa
Enfortumab vedotin 2071301 1291 (11.01-14.92)

Event, NN Median.

o Enforumabvedoin 231301 _5.5(6.32.6.28)
‘Chemotherapy 237/307 894(825-1025) ‘Chemotherapy 248/307 37185239)
®
A HR = 0.74 (95% CI, 0.581-0.852) 3° HR = 0.632 (95% CI, 0.525-0.762)
3 One-sided P = .00015 E ‘One-sided P < 00001
3 Enfortumab vedotin à
= » Enfortumab vedotin
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 eta. Ann Oncol, 2023:34:1047-1054. PeerView.com

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69. EV Monotherapy Showed a Benefit Versus Chemotherapy
Across Exposure Quartiles in EV-3011

+ No evidence that recommended dose modifications impacted long-term efficacy outcomes

4.44 (375677)

0 0, a = 74
: A Ga (27) 116 620821 EV exposure querias
Modan PES 200 Gr 09 (a 7) 562 600720) mor mar max mar
ADC Gr Ot n= 4) 595622723 as
Eu) remota

Chemotherapy (n = 307)

ADC Cay Q1 (n=74) 11.00 (7.89-15.20)
ADC Cm Q2 (n = 74) 15.10 (10.80-NE)
1520 (9.69-NE)

Median OS
RR ADC Cm Q4 (n = 74)
Chemotherapy (n = 307) 897 (05-1074)

12.60 (9.79-NE)

Al data presentes are from a post hoc, exploratory ana
Prop ho EV expours betwen 08-28 02.25%-50%.03:50%-75%.+04:75%-100% (he highest EV exposure quartile), Planned teat amm 7:
1. Petrylak DP et al. ASCO 2024. Abstract 4503. PeerView.com

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70. TROPHY-U-01 Cohort 1: Sacituzumab Govitecan in
Platinum- and Immune Checkpoint Inhibitor-Refractory Settings?

‘Tumor Response to Sacituzumab Govitecan by Central Review per RECIST 1.1
Duration of Response From Start of Treatment to Progression

Govitecan
Target: Trop = ö
epithelial cell
protein highh 2 1 Discontinued without event
vas : > Ongoing response
™ Onset of response
PD or death

OT ESTE OT © OMOTID ITE NOTO NT VO O OZIZRZIZADORO 202,

2021: Accelerated FDA approval Teese.
TROPICS-04°
‘ ORR, % 28
+ Phase 3 trial ongoing (NCT04527991) borane! ae
+ SG vs physician's choice chemo a a
+ Press release: did not meet OS endpoint MPES mo, >
mos, mo 109

FDA approved post-PD-t or PD. inhibitor and a planum containing chemeshorapy
1. rade} (sachuzumab govtecan) Prosenbing Inlormaton, ips accossdata Id goVidrugsaid, docs/abel2023/161115903501 pl.

2.LonotY eta. Ann Oncol. 2024:35:382-40. 3. Gras P e a. J Clin Oncl.306 suppl) TPS408:TP5468. 4. ts www biospace.comvariciegled-s-rodely als u

‘teach primary-ondpointin-confrmatory tl PeerView.com

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71. Trastuzumab Deruxtecan Monotherapy From
DESTINY-PanTumor02 Phase 2 Trial!

Trastuzumab
Deruxtecan

PFS, probability

os 6 9 2 #5 % A 2%

i ‘Time Since First Dose, mo
inhibitor

2024: Accelerated FDA approval for

ladder Cancer mOS,mo 95%

2 3° 134 67-108
HER2+ (IHC3+) 5 MC2+ Bi tows
2 Tos! mee 12454
El
+ MPFS in the bladder cohort was 7.0 mo a
(7.8 mo for IHC2+, 7.4 mo for IHC3+) g Bad cancer MC2*
Bar cancer: mer Biar cancer. Teta
+ MOS in the bladder cohort was 12.8 mo
(13.1mo for IHC2+, 13.4 mo for IHC3+) 56 8 BB BA MD
Time Since First Dose, mo .
1. Meri-Bemstam F etal. J Glin Oncol. 2028:42:47-58 PeerView.com

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72. Using Approved ADCs in the Clinic:
Tactics for Safety Management

Enfortumab Sacituzumab Trastuzumab
Vedotin Govitecan? Deruxtecan*

Peripheral Neuropathy Neutrope Neutropenia
Generally resolves/remains Consider growth factor support Consider growth factor support
‘at grade 1 Dose reduction/delay Dose reduction/delay

Hyperglycemia Diarrhea ILD
Monitor blood glucose in patients + Educate patients really well A tisk of pulmonary adverse
regardless of history of diabetes mellitus Hydration with electro primarily ILD/pneumonitis,
cor hyperglycemia monitor labs has been
ME Antidiarrheal medications/best Corticosteroids
supportive care Team-based management is key

Maculopapular diffuse; manage with
eee a ates e See the Practice Aid for more on
systemic corticosteroids may be used) approaches to adverse event

management in bladder cancer

1. Padcey (etormab vedio) Presrtin nlorabon. aps ww accessdata {Sa govldrigsatsa_docsabel2023761137<024s0250 pa.
2 Trodey (sacturumab govtocar hay Presebing ntrmaton, Nips acessdat Ho govongsatloncorstabel 2023/7011 1Se0898 pal en
3. Enherty (lam-rastuzumab deruxtecan-nxk) Prescribing Information. tps www accessdata fda govidrugsatida_docs/label2024/761 13950281 pa. PeerView.com

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73. Importance of Discussing
Genomic Testing With Patients

Eligibility for Y Flatiron database — Y

FGFR inhibition analysis of >700
requires patients to eligible patients
undergo testing for showed that fewer
genomic alterations than half had
undergone testing!

Of those who were
tested, 21% had an
FGFR alteration but
only 42% received
erdafitinib*

4

Options include specifically testing tumors for FGFR3 alterations
(eg, RT-PCR companion assay) or more comprehensive
approaches (eg, NGS panels, liquid biopsy)
1. Nimgaonkar N et al. JAMA Oncol.2022.8:1070-1072.

Testing ideally
occurs at the time
of diagnosis of
metastatic disease

PeerView.com/GJT827

Goal: To offer patients
the full range of available
therapeutic options to ensure the
best possible outcome

PeerView.com

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74. Erdafitinib in FGFR-Altered Metastatic or Unresectable UC

Phase 3 THORS:
Where should FGFR3 inhibitors be integrated into
the treatment regimens of patients with mUC?

\ Cohort 1

Phase 2 BLC2001'°;
Erdat ib Monotherapy

+ Long-term efficacy outcomes

showed that patients derived

7

Key Eligibility Criteria

+ Patients with metastatic or Erdafitinib

DOR, PFS, and OS benefit unresectable locally

from erdafitinib, regardless advanced UC

of FGFR alteration type, tumor o ere

location, presence of visceral with en anti-PD-L1 agentes Centra
metastases, or prior treatment monotherapy or as ra
with immune checkpoint (combination therapy: <2 prior |”| y, Lone o
inhibitor lines of systemic treatment

mutations

+ Cohort 2: no prior treatment
with an anti-PD-L1 agent;
only 1 line of prior systemic
treatment Pembrolizumab

+ ECOG PS0-2 I 3

+ 2019: accelerated FDA
approval for mUC with an
FGFR3- or FGFR2-activating
mutation or fusion after
progression on 21 line of
platinum-containing chemo

+ Primary endpoint: OS
+ Secondary endpoints: PFS, ORR, PROS, DOR, safety

4. Lost Y ta N Eng! J Med. 2019:381:38-348. 2. Necehi A etal. Ann Oncol. 2020:3H(supp 4550 E
3, Siofker-Radike otal. Lancet Oncol. 2022:28:248-258. 4. Loriot T et al. N Engl J Med, 2023;389:1961-1971, PeerView.com

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75. Phase 3 THOR: Cohort 1
(Erdafitinib Versus Chemotherapy)"

MOS: 12.1 mo vs 7.8 mo
HR = 0.64 (95% Cl, 0.47-0.88)
005

MPFS: 5.6 mo vs 2.7 mo
HR = 0.58 (95% Cl, 0.44-0.78)
P=.0002

1
1
1
1
1
1
1
1
1
© 1 o
x sz
g E
o 1.
1
1
» 1 »
ERDA |
‘CHEMO 1 ;
a ee ee eee CE Ku SUCHE HE HE À À EHE à
en Time Since Randomization, mo 1 Time Since Randomization, mo
ve a ES
Es we O7 D 4 3 2 8 5 3 3 2 2 2 4 0 pee ® Da ae 7 3 3 3 ? 4 4 0
om mer eo D 0 M 9 8 3 2 2 1 0 0 0 0 © jam mo a 9 4 2 2 1 1 + 0 0 0
1
1
1
1
* Median folow-up: 15.9 mont. ñ
1: LoñotT at al N Engl J Mod! 2023:389:1961.1971 PeerView.com

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76. Phase 3 THOR: Cohort 1
(Erdafitinib Versus Chemotherapy)"

2024: Full FDA Approval for

en locally advanced or mUC with
select FGFR3 alterations
progressing on
40 21 PD-1/PD-L1 inhibitor?
= RR, 3.94 (95% Cl, 2.37-6.57)

P<.001

x
g
E
&

20

ORR: 11.5 CR: 0.8

—
10

o
Erdafitinib Chemotherapy
(n= 136) (n= 130)
"Median followup 15.9 months
1.Lonet Total. N Engl) Mod. 2023:389:1961-1971. ñ
2. ps tw fda govirugsiresources-information-approved-drugs/da-approves-erdaftinittocally-advanced-or-metastatc-urothelial-carcinoma, PeerView.com

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77. Phase 3 THOR: Cohort 2

(Erdafitinib Versus Pembrolizumab)'2
Ñ Sore roses ua a
: EST EEE oy ol mes mispmaises
il e
a. 3 ;
#. i
CRE ee

| Primary endpo inib demonstrated numerical better PFS and

RR but shorter Di embrolizumab

For patients with FGFR alterations, pembrolizumab should be used before erdafitinib if the
patient has not received prior immunotherapy

1.Sieker-Radike A et al. Ann Oncol. 2024:36:107-117. 2. Sioker-Radike A

al ASCO 2024. Abstract 4578, PeerView.com

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78. Using Erdafitinib Therapy in the Clinic:
Tactics for Safety Management"?

Close monitoring and supportive care is important; oral hygiene critical

+ Mucositis and other oral toxicities
— Maintaining good oral hygiene is critical

+ Monitor for skin toxicities

+ Refer to dermatology and podiatry as needed
— Moisturizers for dry skin (urea and salicylic acid-containing preparations may be helpful)
— Use heavy creams for hand-foot syndrome; topical steroids may be used for > grade 2
— Minoxidil for alopecia

+ Monitor for nail toxicities

— Gentle trimming and filing of nails
- Use of gloves and moisturizers

1. LovotY et al. N Engl J Med. 2019:81338-348. 2 Sifker-Radike etal Lancet Oncol 2022:23:248-258. PeerView.com

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79. Using Erdafitinib Therapy in the Clinic:
Tactics for Safety Management!

Hyperphosphatemia Ocular Toxicities

. Eat ges ques Lo signaling + Recommended ophthalmologic examinations
in the proximal renal tubule, impairing _ E
function ofthe sodium-dependent Monthly for first 4 mo; every 3 mo thereafter

— At any time for visual symptoms
+ Consider dose reductions as needed
+ For any occurrence of CSR/RPED
— Withhold erdafitinib; discontinue permanently
if symptoms do not resolve in 4 wk
- Discontinue permanently for grade 4
CSR/RPED

phosphate co-transporter
+ Dietary phosphate may require restriction
— Consult a nutrition professional
(eg, registered dietitian, nutritionist)
for individualized dietary planning
— Consider adding a non-calcium-containing
phosphate binder (eg, sevelamer carbonate)

1.Lodo Y et al. N Engl J Med. 2019381:338-%48. 2 Sifker-Radike et al. Lancet Oncol 202223:248:25. PeerView.com

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80. Tool to Support Patients Searching
for Clinical Trials in Bladder Cancer

Mr
ate <= The BCAN Clinical Trials dashboard can Cinial Tle
BCAN be used to find a trial that fits an individual mens
ie Caer React patient's needs
+ Healthcare professionals can save trials and email them to

patients for further discussion at their next visit

Patients can search by geographic area and find trials close
to/convenient for them

See the BCAN Practice Aid for full details on the BCAN website,

a QR code for professionals to download resources for patients,
and more!

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81. Kyle: A Patient With Progressing mUC

Panel Discussion

PeerView.com/GJT827

69-year-old man with mUC

received 4 cycles of carbo/gem ï
loue by maintenance What 2L options would you

avelumab discuss with Kyle?
CT showed liver and bone mets >

ECOG PS 1

NGS of primary bladder tumor
tissue showed FGFR3 S249C
mutation

Grade 2 neuropathy

No autoimmune, eye, skin, nail,
or Gl issues
Uncontrolled diabetes
(HbA1c 9%)

+ How do comorbidities play into treatment
decisions/treatment sequencing?

+ What day-to-day expectations would you
discuss with Kyle before initiating therapy?

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82. Audience Q&A 7

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