Harnessing Innovation in Bladder Cancer Care: Strategies for Effectively Implementing Modern Therapeutic Advances Across the Disease Continuum

Chair and Presenters, Neal D. Shore, MD, FACS, Ashish M. Kamat, MD, MBBS, and Joshua J. Meeks, MD, PhD, discuss bladder cancer in this CME/MOC/NCPD/AAPA/IPCE activity titled “Harnessing Innovation in Bladder Cancer Care: Strategies for Effectively Implementing Modern Therapeutic Advances Across the Disease Continuum.” 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/3PH0RVQ. CME/MOC/NCPD/AAPA/IPCE credit will be available until June 2, 2025.

1. Harnessing Innovation
in Bladder Cancer Care

Strategies for Effectively Implementing Modern Therapeutic

Advances Across the Disease Continuum

Neal D. Shore, MD, FACS Ashish M. Kamat, MD, MBBS
Medical Director, Carolina — Professor of Urologic Oncology
Urologic Research Center y Wayne B. Duddlesten Professor of Cancer Research

Myrtle Beach, South Carolina Director, Bladder Cancer Research, Department of Urology
Yi The University of Texas MD Anderson Cancer Center
Houston, Texas

Joshua J. Meeks, MD, PhD

Associate Professor of Urology

Departments of Urology, Biochemistry and Molecular Genetics
Feinberg School of Medicine, Northwestern University
Chicago, Illinois

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

[3]

> 2000-2024, PeerView

2. Our Goals for Today

Augment your understanding of current and emerging data for the
treatment of bladder cancer utilizing bladder-sparing and
perioperative approaches, advanced drug delivery techniques, and
modern immunotherapy regimens

Equip you with the skills you need to integrate these modern
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

3. BCAN Is an Excellent Resource for

Professionals, Patients, and Care:

ers

When diagnosed with bladder cancer, patients and their caregivers may feel

BCAN.

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
Animated videos
Webinars
Podcasts
Treatment matrix

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Clinical trials
dashboard
Bladder Cancer
Support Line: call
(833-ASK-4-BCA)

overwhelmed by the amount of treatment options for urothelial carcinoma.
BCAN provides educational resources to help patients feel more prepared.

der cancer patients

le give
end caregivers the resoufaag. and
‘support they need to cope
the disease.

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4. 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?

» Development of effective, safe, and
durable intravesical treatment

remains a critical unmet clinical
need for patients who want to avoid

Close to half of patients with MIBC

worldwide may not receive curative i

intent therapy?

Patients who have undergone
radical cystectomy for MIBC often
have impaired HRQOL and a high
risk of recurrence*>

1. Tyson M et al J Cin Oncol. 2019:37(supp 1518012. 2. ps www auanet rg/about-us/begahorage nt. mn:
3 Westergren DO et a. J Ure! 2019:202 905.012 4. Cho Het al Trans! Andre UL 2020;9 2097-2008, 5, Roupret Met al Eur Urol 2021795279. PeerView.com

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5. Team-Based Care of Patients With Bladder Cancer

>
Numerous FDA-approved + Urologists, often the first point of contact for
agents and clinical trials patients, need to be familiar with the range
underway have changed of available treatment options at various

the approach to disease stages

management of bladder + Patient education must focus on the

cancer across the importance of prompt recognition and
disease continuum management of AEs

|

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6. Utilizing Therapeutic Innovations for
Effective Management of NMIBC

Ashish M. Kamat, MD, MBBS

Professor of Urologic Oncology

Wayne B. Duddlesten Professor of Cancer Research
Director, Bladder Cancer Research, Department of Urology
The University of Texas MD Anderson Cancer Center
Houston, Texas

2000-2024, PeerView

7. What Is the Standard of
Care for High-Risk NMIBC?

8. International Bladder Cancer Group Risk Categories‘?

Risk Category Tumor Characteristics Outcomes

Ta low grade (LG):

row nek. solitary, primary, and s3 cm

Low risk of recurrence/progression

Anything that falls between low risk

Intermediate risk and high risk

Recurrence is main concern

Any HG (Ta, T1, CIS)
Any TA

Progression is main concern

High risk: 30% progression, ~75% recurrence
Low risk: <5% progression, ~45% recurrence

1. Kamat AM et al. J Cin Oncol 2016:4:1935-1044. 2. Roumigulé Metal. Eur Ure, 20221823446. PeerView.com

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9. Standard of Care for High-Risk NMIBC—
Numerous Guidelines

A Air i Csitc Society for Immunotherapy of Cancer

Association

Explain the rok and
condor radial

eal Guidelines

Tntravecal ECG for. ye. (Stone)

Cystoscopy and evtology at 3 mo.
{stron
negative cystoscopy and cytology

TERNATIONA\ ramo lavan eno
LAD e i thereafter until 5 yr. and then yearly
LADDER CANCER National Comprehensive ea ees
GROUP NAO Cancer Network" ;

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10. Standard of Care for High-Risk NMIBC—
Numerous Guidelines

Poa I

ila , 2

| BCG is the
il

[Cancer

ORIGINAL

Tntravecal BCG for 1 yr. (Strong)

Cystoscopy and cytology at 3 mo.
{strove

octave, ptoscopy and cytology

IN '3 mo. for 2 vr. 6 mo.
se . De,
BLADDER CANCER National Comprehensive een "
GROUP NA Cancer Network” T

@

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11. Classification of BCG Failure’

Persistent HG disease at 6 months despite adequate BCG
BCG refractory + Also includes any stage/grade progression by 3 months after ¡BCG cycle
(ie, T1HG at 3 months after initial Ta, or CIS)

+ Recurrence of HG disease after achieving a disease-free state at 6 months
following adequate BCG
+ Previously subdivided based on time to recurrence after stopping BCG
(ie, early [<12 months], intermediate [1-2 years], or late [>24 months])

BCG relapsing

BCG intolerant + Disease persistence due to inability to receive adequate BCG due to toxicity

BCG refractory + BCG relapsing disease (within 6-12 months of last
BCG exposure)

BCG unresponsive Meant to denote a subgroup of patients at highest risk of recurrence and
progression for whom additional BCG therapy is not a feasible option
These patients can be considered for single-arm studies

1. Kamat AM eta. J Cin Oncol 2016:34:195-1944, PeerView.com

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12. International Bladder Cancer Group Consensus Statement
on the Definition of BCG-Exposed High-Risk NMIBC!

NMIBC Recurrence After BCG Treatment

Treatment BCG induction only Adequate BCG Inadequate B

Stage/grade High grade
of recurrence
Time to event mo after
start of
+
Disease sete

1.Roumigui Met al, Eur Url 2022:82:3446 PeerView.com

Adequate BCG:
25 of 6 doses of iBCG
plus 22 additional doses
of mBCG

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13. Pembrolizumab Monotherapy for
BCG-Unresponsive, High-Risk NMIBC'

KEYNOTE-057 Cohort A: CIS + Papillary Disease (High-Grade Ta or T1)

de Best Response

an n DOR (rang CR 39(40.6) 30.7-51.1
go pd Non-CR 56(583) — 47.8:-68.3
= Progression to T2 o NA

= NE 1 (1.0) 0-5.7
i + Upstaging to 2pT2 in 8.3% of patients

É Extended minimum follow-up of 26.3 mo

2 + OF 39 responders, 13 (33.3%) remained in CR

218 mo and 9 (23.1%) remained in CR 224 mo
as of the data cutoff date
+ No new safety risks were identified

3 6 9 2 15 18 21 2 27 30 33
Time, mo

January 2020

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

4. Baar AV et al Lancet Oncol, 2021:22010-690 PeerView.com

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14. Gene Therapy for NMIBC

Nadofaragene firadenovec: a nonreplicating adenoviral vector-based gene therapy that delivers human
IFNa2b-cDNA to urothelial cells and Syn3 to enhance viral transduction to the urothelium. /FNa2b-cDNA is is

Lo maus cu

Gr of IFNazb mcs
=> a fe
Or December 2022
First gene therapy approved by the
hw FDA for the treatment of adult
=> ZEN patients with high-risk,

BCG-unresponsive NMIBC with CIS

{: Beja SA ea Lancet One 202122 1071172 Bojan SA et a SUO 2023. Abstract 184.3. Narayan VA el Front Oncol. 202414196025,

4! Boorjan SA et al EAU 2024. Abstract ADSE. PeerView.com

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15. Nadofaragene Firadenovec: Sustained Responses
in BCG-Unresponsive NMIBC1-3

36-Month Efficacy of Nadofaragene Firadenovec in Patients cis PD

With BCG-Unresponsive CIS + Ta/T1 (Efficacy Analysis Set) alle

Patients Free From High-Grade Recurrence Durability of CR

. rh e es CR at3 mo, % 534 729
ma x Free from high-grade
q Lo 764 recurrence at 3 y, % 258 14
ess
iu iu MDOCR, mo 97 97
= el 200 Median duration of high- Pr dd
i i 255 grade RFS, mo
pa Pe Estimated 3-y CFS rate, % 538 636
o o OS rate, % 90. 90.7
em mm ECC
Time From First Nadofaragene Time From First Nadofaragene
Fradenovee Adminstration, mo Firadenovec Administration, mo

Intravesical nadofaragene firadenovec, adı

* High-grade TarT1 papilary disease. u
1. Boonan SA et al. Lancet Oncol 2021:22:107-117, 2. Boorjan SA et al. SUO 2023, Abstract 164.3. Boorian SA et al. EAU 2024, Abstract ADSES. PeerView.com

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16. Additional Studies for

ADSTILADRIN in BLadder CancEr (ABLE)'*

Phase 3b
ABLE-32

Phase 4
ABLE-41

Phase 4
ABLE-42

Safety and efficacy of nadofaragene firadenovec + chemotherapy
(gemcitabine or docetaxel) or immunotherapy (pembrolizumab) in
with BCG-unresponsive NMIBC

Safety and efficacy of nadofaragene firadenovec versus observati
with intermediate-risk NMIBC

Prospective non-interventional study to collect data on the early us

nadofaragene firadenovec in the United States; data will be collected from
participants, caregivers, and prescribing physicians in a real-world setting

Efficacy of retreatment with nadofaragene firadenovec in patients

BCG-unresponsive NMIBC with CIS + papillary tumors who did not respond to
previous treatment with nadofaragene firadenovec at 3-month follow-up

patients

ion in patients

ise of

with high-grade,

1. Daneshmand S et al. ASCO GU 2024. Abstract TPS70S. 2. tps www cicalials govstudyINCTOG026332. 3, ps www cnicatials govstudyINCTO6300111,
4. ps vw biospace.com/arceltelessesTeriing-adde-hree-new-sties-to-non-muscle-nvasive-bladder-cancer-clnical-vah-programm-tiradstladrn-

nadofaragene fradenoveemeg

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17. Gene Therapy for NMIBC

Oncolytic adenovirus: scretostimegene, Brsnadengrenyec, EUA

Oncolytic Immunotherapy: Selective Oncolysis and
Potent Anti-Tumor Immune Response

‘Spreads o additonal tumor cells

“Torgeting and Destroying Study Administration Schedule

Induction Induction 2 Maintenance/Foliow-Up
mono 3 s ° 2 . 1 a

E
¡UI
= os =e

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18. Gene Therapy for NMIBC: Phase 3 BOND-003'

Oncolytic adenovirus: cretostimogene grenadenorepvec (CG0070)

Cretostimogene

Response Evaluation Monotherapy
% (NN) 95% Cl
CR
At any time 75.7 (50/66) 63-85
At3 mo 68.2 (45/66) 55-79
At6 mo 63.6 (42/66) 51-75
Duration of CR
23 mo 84.0 (42/50) 70-92
26 mo 74.4 (32/43) 58-86

1. Tyson MO et al. SUO 2023. Abstract 3306.

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— Ongoing response
= Complete response
+ Non-response

% Discontinued study
> Re-induced

o 3 e 9
CR Assessment, mo
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19. IL-15 Superagonist (NAI/N-803)'

N-803 IL-15 Superagonist Antibody Cytokine Fusion Protein

cytokine Antibody (IgG4Fe)
(L-15N720) Increases haltite (FeRn receptor) and

increases homing to CD16 receptor

Cytokine Fusion
(L-418Ra)

Antibody (1961 Fe):

IL-15N72D and 1961 Fe target,

activate, and proliferate endogenous

king cells NK, CD8* T cells without
inducing T reg stimulation

1.Chamie K et al. J Gin Oncol 2021;38(supp 8510.

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ILASNT2D

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20. IL-15 Superagonist (NAI/N-803)1

Time to CR and Duration of CR Key Efficacy Results

=— 71%

CR rate at Median

any time duration of CR

Patients With CR

A CR: 71% (68/82)
‘Ongoing response (n = 28);

> Ongoing response, til on study (n = 21)

>» Completed 24-mo study and not continued on study (n = 7)
+ Recurrent high-grade NMIBC (n = 25)
«Discontinued (n = 5)

I 6 8 D & 8 À À D 0 8 36
Time Since First Dose of Study Drug, mo
* Vitro, death unrelated o treatment lst to folowup received other therapy.

Shami iat NES Evers, 20292 EVO OZ, Hi a Gorges female apro dde apro D OA CU COM
‘nbakicept pmin-beg-unresponsive-non-musciemvasive-bladder-cance” A

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21. Advances in Therapeutic Strategies for NMIBC:
TAR-200 Intravesical Drug Delivery

FDA Breakthrough

TAR-200 Therapy Designation

SunRISe-11 4: Cohort 1: TAR-200 +
cetrelimab (n = 100)

Key Eligibility Criteria Primary endpoint:
+ BCG-unresponsive, high-risk NMIBC Cohort closed overall CR rate
+ ECOG PS 0-2

+ With or without papillary disease Cohort 2: TAR-200* (n = 80)

(T1, high-grade Ta)
+ Ineligible for or declined RC

Key secondary
endpoints:
DOR, OS, safety

Key Eli © ia Primary endpoint:
+ HR NMIBC papillary disease only (no CIS) DFS rate

% TAR-200 dosing: Q3W (inweling) fr frst 24 weeks: then Q12W through week 86.
1. htpsetincatnals govstudyINCTO4640625,

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22. SunRiSe-1:
BCG-Unresponsive, High-Risk NMIBC13

CR Rate in Patients With High-Risk NMIBC CIS
100 (Cohort 2)° Treatment Duration and Response to TAR-200 Monotherapy

Median DOR has not been reached
Median follow-up in responders was 48 wk (range, 12-21)
Kaplan-Meier estimates for DOR rate
+ 6 mo: 93% (95% Cl, 61-99)
+ 12 m0; 84% (95% Cl, 49-96)

Overall CR Rate, %

Centrally Assessed Investigator Assessed
(n= 30) (n= 30%

Patients (N = 54)

1% (21723) responses are ongoing

Noam soca ape) | „Aare
eme | Se
+ Updated data: CR = 82.8%

= None ofthe patients with CR have undergone

+ TAR-200 was well tolerated; mainly low-grade 1 or 2 radical eystectomy

20» El
Time, mo

"Overall CR rate is based on CR at any time. "The effeacy analysis was performed on al rated patents who have active disease at baseline and adequate disease

‘assessment post baselne, or who have progressed ded due 1 recurrence of hh sk disease cr progressive disease, or have discontinue the study

<A CR is defined as having a negative cystoscopy and negative (ncluding atypical) central read urine cology or posihve cystoscopy with biopsy-proven benign or

low-grade NMIBC and negative (ncluing aypca) centaly read cytology at any tme point

1. Daneshmand S et al AUA 2023, LBA 02-03, 2. Necch A et al. ESMO 2023. LBATOS, 3. Jacob Jet al. AUA 2024. Abstract P201

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

Group A (n = 350)
a eee aa TAR-200 (gemcitabine 225 mg Q3W [induction phase]
eater is Ea ap and Q12W [maintenance phase]) + cetrelimab
confirmed high-risk NMIBC
(high-grade Ta, any T1, or CIS)* a ESO)

BCG-nalve (no prior BCG, or vk [induction] and QW for 3 wk at

last exposure >3 y prior to 2 48,72, a
randomization)
Group C (n = 350)

Age 218 y
ECOG PS 0-2 TAR-200 (gemcitabine 225 mg Q3W [induction phase]

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

96 [maintenance])

Primary endpoint: EFS (time from randomization to first occurrence of HR disease, progression,?

or any-cause death, whichever occurs first®)
Secondary endpoints: Overall CR rate (CIS only) duration of CR,* RFS, TTP, OS, cancer-specific

survival, safety and tolerability, patient-reported outcomes
A ible ppl soso must be uy rnece (bean) rico randomizao end documenta a Luce ca rine coy at screning must be negative or apical or
grade UC in pants wth paplayıany nes, Al AEs associated wih any prior surgery ander mare erapy must have reses fo CTCAE v5.0 rade <2 pio randomization
"Poren deine sage nrease rom Ta 1 Ti rom Gis 1 T1 progre le MC (122) or mph nose (Ws) or ants) ease, hate seers Wak
“For patents wih CI. Persien eave sl mol ano conser an EFS event patents wan CS wha have no presence of HR sean at 6 mo
“Time om rt CR cave 1 fst erden ol recrence progression, or any cose sath, whichever cere =
1. Mips:elnicatrils gow/studyINCTOS7 14202. PeerView.com

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24. SunRISe Trials Underway’

+ TAR-200 + cetrelimab versus cetrelimab alone in
BCG-unresponsive NMIBC

+ TAR-200 + cetrelimab versus concurrent
chemoradiotherapy in MIBC

SunRISe-1

'SunRISe-2
+ TAR-200 + cetrelimab versus intravesical BCG in
BCG-naive high-risk NMIBC

+ TAR-200 + cetrelimab as neoadjuvant therapy
in MIBC

* TAR-200 versus intravesical chemotherapy in
recurrent, high-risk NMIBC after BCG

SunRISe-4

SunRiSe-5

Y tps eier go PeerView.com

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25. FGFR Mutations Are Frequently Observed
in Bladder Cancer!

Non-Muscle Invasive Muscle Invasive

>60% 30%
1

4. Knowles MA et al. Nat Rev Cancer 2015:152541 PeerView.com

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26. TAR-210: Erdafitinib Intravesical Delivery?

Cohort 1
+ High-risk NMIBC Response is assessed every 3 mo with
(high-grade Ta/T1, no CIS continued treatment for up to 1 y if
do recurrence-free (cohort 1) or CR (cohort 3)

Molecular Eligibility Boreas
er unresponsive and not Part 1 Part 2

eiigibility strategy is used receiving RC Dose Escalation Dose Expansion

to detect FGFR alterations | | OI TOC
+ Local or central fresh/ e! Expansion Cohort 1
een disease prior to treatment

OR

= Intermediate-risk NMIBC, + Non-RC patients: cohort 1 .
eee DNA recurrent, history of and cohort 3 combined Expansion of both
E grade only Ta/T1 disease + Placement every 3 mo dose levels
Visible target lesions prior
to treatment
(chemoablation design)

+ Primary endpoint: safety (AEs, AE severity, DLT)

* Clinical eo date: August 29,2023. Two deren erdaftin release rates are being evaluated. A
1. ps cinicalras gowstudyINCTOS3 16185. 2. Viaseca A et al. ESMO 2023. LBA1OS. PeerView.com

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27. TAR-210 Provided High Rate of Response’

Cohort 3: FGFR-Altered Intermediate-Risk NMIBC (N = 27)
CR rate: 87%

Cohort 1: FGFR-Altered High-Risk NMIBC (N = 16)°
Recurrence-free rate: 82%

TAR-210-0(n= 13)

m TAR210.0(0=7)
m TAR210.8(0=9) = TAR210-0(0= 14)
> Median duratonoftreatmentexposue Response Response

win TAR-210-0:43 mo (range,29) © Recurtencetroe

un Megan duatoneftreatmentexposurewih $e Non-CRINon-PD

TAR210.0.3. mo (range, 0-10)

» Treatmentongoing » Treatrentongoing

Patients

x Treatment reser
discontinvason x Treatren
1 Treatment completes Pi eins A
Median duratonoftreatmentexposure = Follow-upperog —
with TAR-210:8:3.7 mo (range, 2-12) in
Median duratonoftreatmentexposure with
TAR-210-8: 42 mo (range, 1-12)
ry 180 zu 360 450 ps 180 270 260 450

‘Treatment Duration, d Treatment Duration, d

Phase : MoonRiSe-1 | Underway? TAR-210 vs IV chemotherapy à patients with
interme: FGFR alt

* Patent characteris (= 16): medan age, 7. y (ange, 62.90} 75% were mal; 75% and 25% had tumor sage Ta and TI, respecte 44% had mute
timos 100% had per 806. Patent characterises (N= 27) medan age 67 y (age, 41-37) 85% were mal; 100% had mar tage Ta: 41% had mull ur

22% had poor BCG, 50% had po inravescal chemotherapy. Fa

1. Vilaseca À et al. ESMO 2025, Abstract LEA 104.2. ps /lnicavialsgov/studyINCTOS3 19820. PeerView.com

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28. Stuart: A Patient With NMIBC

What options will Stuart have for
therapy now and in the future?

64-year-old patient 5 -
with high-risk NMIBC Panel Discussion

Good performance status Practical points/tips on using:
a o — Pembrolizumab
2 induction courses of BCG LER = Nadofaragene (every 3 mo)?

— N-803?
— TAR-200, TAR-210, CG0070
approaches?

Undergoes repeat TURBT
Recurrent CIS
Refuses RC

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29. Trimodal Bladder-Sparing
Opportunities

Joshua J. Meeks, MD, PhD

Associate Professor of Urology

Departments of Urology, Biochemistry and Molecular Genetics
Feinberg School of Medicine, Northwestern University
Chicago, Illinois

Copyright

2000-2024, PeerView

30. Trimodality Therapy (TMT) in MIBC

+ Complete transurethral resection of the bladder tumor followed
by radiotherapy with chemosensitizing chemotherapy |

| + Valid alternative option to RC for patients with MIBC who would
like bladder preservation |

+ Lack of randomized clinical trials assessing trimodality vs RC |

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31. Analysis of RC Versus TMT in the Setting of a
Multidisciplinary Bladder Cancer Clinic!
Retrospective study comparing the oncologic outcomes in patients treated

with RC versus TMT by using a propensity score-matched cohort analysis
(N= 112)

+ Cohorts matched for cT and cN stage, ECOG PS, Charlson score, treatment
date, age, CIS status, and hydronephrosis

+ TMT eligibility: more liberal (tumors <5 cm, mild hydronephrosis, adjacent CIS)

* >cT2: 26.8% in RC cohort vs 32.1% in TMT cohort

+ 19.6% in RC cohort received NAC

+ 20 deaths in RC cohort vs 22 deaths in TMT cohort at a median of 4.51 years

No difference in OS (H 85; P = .63) at a median of 6.61 years

1.Kukami GS eta. J Gin Oncol 20173 22962308. PeerView.com

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32. TMT: Improved Quality of Life

Questionnaire of 6 validated QOL instruments

N = 226 disease-free patients
77% questionnaire response rate (n = 173; 72% RC vs 86% TMT)
RC group (82% IC, 17% neobladder)

Median interval from diagnosis to questionnaire completion:
7 years for RC group vs 9 years for TMT group

Higher local failure in TMT vs RC (22% vs 1%)

Better pupctional outcomes in TMT vs RC

GOL instuments used: EuroQOL EQ-5D, EORTC Qualty of Life Core Questionnaire, EORTC MIBC module, Expanded Prostate Cancer Index Composite bowel
scale. Cancer Treatment and Percepion Seale, and impact of Cancer, version 2 a
Mai KS eta. Int Racit Oncol Biol Phys, 2016:96 1028-1036. PeerView.com

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33. Concurrent Chemoradiotherapy!

Cancer-Specific Survival Overall Survival
Chemoradiation 1 zu
Is the Standard of Care ig one i
Patient-favored treatment for MIBC i a 3
Current approach favors cT2, la E
minimal CIS, no hydronephrosis i 2%
Can recur locally (NMIBC/MIBC) © a
mime Time From Treatment y
oncology and Cystectomy-Free Survival
qu
H 0
Ecos 2004-2008 (n
om — = 2009-2013 (n = 452)
pe €.
=
Em
ST
Tae on Teste,
1. Ghate K et al, Ragioher Oncol 2018:127:136-142. PeerView.com

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34. TMT: Current Standards!

Urologist

TURBT Medical Surveillance
MIBC oncologist Cysto

Radiation
oncologist

1.NCON Cinical Practice Guideines in Oncology. Bladder Cancer. Version 3.2024. htps/www.ncenorgprofessionaliphysician_olspdtibladder pat PeerView.com

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35. Harnessing 10 for Trimodality Therapy in MIBC

Phase 3 $1806: Randomized Trial of Concurrent Chemoradiotherapy + Atezolizumab in Localized MIBC*

Primary endpoint: bladder-intact EFS*

Secondary endpoints
OS at 5 years
Clinical response at 5 months

cT2-T4NOMO 4 = -
Stratification HIN Concurrent à
Chemotherapy CRT alone es
regimen as
Radiation field 5
Performance status ©
Clinical stage Concurrent
CRT + Atezo

N= 484

+ Bladderintact EFS includes: Muscle-nvasverecurence inthe bladder regional petv sof bssue or nodal recurence:
distant metastases, bladder cancer o loiey-elated death. eystectomy Mi
1. tpsiinicatials govistudyyNCTO37?5265. PeerView.com

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36. Harnessing IO for Trimodality Therapy in MIBC

Phase 3 KEYNOTE-992: Pembrolizumab + Chemora

therapy Versus Chemora

therapy Alone!

Cystoscopy,
urine cytology,
biopsy as
indicated, and

Pembrolizumab
400 mg IV (
for~ty

Pembrolizumab
Q

Cystoscopy, urine
cytology, biopsy of
tumor bed, and

(T2-T4 NOMO)
+ Opting for

imaging Q12W

imaging 10 wk (+ 2 wk)
ps Placebo IV (£2 wk) after CRT through year 2
pr CRT Q24W (+ 2 wk)

ss (n=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

1. Tissot G et al Eur Uro Focus. 20239227228 PeerView.com

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37. Harnessing IO for Trimodality Therapy in MIBC

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

Key Eligibility Criteria
Patients with MIBC
cT2-T4a, NO, MO
Not receiving RC

Stratification®

Cetrelimab + TAR-200
Q3W (indwelling) for first 18 wk; then
starting on week 24, Q12W through
study year 3

Assessments until
histologically proven presence
of MIBC, clinical evidence of

. oe (visibly nodal or metastatic disease
c VS (per RECIST v1.1), radical
incomplete [residual Cisplatin 35 mg/m? QW x 6 wk or cystectomy, death, or end of
tumor <3]) gemcitabine 27 mg/m? Q2W x 6 wk study, whichever occurs first

+ Tumor stage (t0 vs investigator's choice) + E

Ta/T1/Tis vs T2-T4a)
N=~550

radiation therapy?

+ Primary endpoint: bladder-intact EFS

* Based on screening e-TURBT. * Investigator’ choice of conventional adotherapy over 6 5 weeks or hypotactonated radiotherapy over 4 weeks un
1. Mis chicahral.gov/studyNCTO4658862. 2 Willams S8 etal ASCO 2021. Abstract TPSASE6. PeerView.com

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38. How Far Can We Take
Bladder Preservation?

ht © 2000-2024, Peerview

39. Neoadjuvant Phase 2 Studies: Immunotherapy Alone
and Immunotherapy + Chemotherapy

immunotherapy PCR, %

PURE-01 (N = 50)* Pembrolizumab 42
ABACUS (N = 95)? Atezolizumab 31
NCT02812420 (N = 54)? Durvalumab + tremelimumab 37.5
NABUCCO (N = 24) Nivolumab + ipilimumab 46

Immunotherapy +

Chemotherapy

BLASST-1 (N = 41)5 Nivolumab + gem/cis 34 BLASST-11011
HCRN GU14-188 (N = 43)6 Pembrolizumab + gem/cis 44 L
NCTO2690558 (N = 39)" Pembrolizumab + gem/cis 39

NCTO2989584 (N = 39)° Atezolizumab + gem/cis 38
SAKK 06/17 (N = 52)? Durvalumab + gem/cis 33

1. Necehi À et al. J Clin Oncol 2018:36:3383-3360. 2. Poules Tet al. Nat Med. 201025:1708-1714.3. Gao J etal Nat Med. 2020:26:1845-1851.

4. van Dik N et al. Nat Med. 2020.26:1839-1844. 5. Gupta S et al. ASCO GU 2020, Abstract 439, 6. Holmes CJ et al. ASCO 2020. Abstract 5047.

7. Rose TL et a. J Cin Oncol, 2021;30:3140-3148, 8, Funt SA et al. Cin Oncol 2022.40-1312-1322. 9, Cathomas R etal. J Cin Oncol, 2023:41:5131-6139.
10. Gupta S etal SUO 2022. Abstract 14. 11. Gupta S et al ASCO GU 2023, Abstract 55.

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40. Several Ongoing Phase 3 Trials With
Perioperative Immunotherapy

Cisplatin El

le Cisplatin-Eligible Trials

Neoadjuvant phase Adjuvant phase CA017-0781

Gem/cis + nivolumab
(fully accrued N = 861)

10
or
10 + novel agent

10 + chemo
or
10 + novel agent

NIAGARA?
Gem/cis + durvalumab
(fully accrued N = 1,063)

KEYNOTE-866*
Gem/cis + pembrolizumab
(fully accrued N = 907)

Placebo + chemo Placebo

Radical cystectomy and
pelvic lymph node dissection

1. tps inicaltials gowstudyINCT03661320. 2. hps/cnicarials govstudyiNCT03732677. 3. ts cnica gowstodyINCTO3824856, =
4: ts chic govstudyNNCTO4700124, PeerView.com

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41. Several Ongoing Phase 3 Trials With
Perioperative Immunotherapy

Cisplatin Ineligible

Neoadjuvant phase Adjuvant phase

10+ 10+
novel agent novel agent

Observation

Radical cystectomy and
pelvic lymph node dissection

1. ps ciniciriais gov/stadyINCTO3024806. 2. tps clinical govistudyINCTO4960709. 3. Poules Tet al. ASCO GU 2022. Abstract TPSS7O,

4. Ms ilnicalials govistudyINCTO4919512. 5, Psuka SP etal, ASCO GU 2023. Abstract TPSS84

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Cisplatin-Ineligible Trials

KEYNOTE-905/EV-303'
Pembrolizumab + E

VOLGA?3
Durvalumab + tremelimumab
+EV

SunRISe-445
(phase 2)
TAR-200 + cetrelimab

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42. Updating Bladder-Sparing Paradigms

Survival of Patients With or Without TURBT + Chemotherapy Associated With Long-Term
Pathological CR After NAC* Bladder-Intact Survival in a Subset of Patients?

10

Pathological CR No Partial Radical
(n= 314; 41 died) Outcomes Cystectomy Cystectomy Cystectomy|
(n= 28) (n=15) (n=17)

ae Invasive local relapse,n(%) 8 (29) 5 (33)
E en 10-y survival
e No pathological CR "~~~ Overall, n (%) 21 (75) MB) 11(65)
& Log-rankP<.0001 (n= 1,239; 646 died) Bladder intact 1761) 363) o
o
° 7 7 y y o P 3 5
mé openly Paucity of prospective studies

Lack of rigorous methods to measure
Historical Barriers and define clinical CR

A pathological CR is achieved in ~30%-40%
of patients with cisplatin-based NAC for MIBC
and is associated with favorable outcomes

to This Limited understanding of the role of
Bladder-Sparing an patients with
Paradigm cal Te

Paradoxically, a pathological CR can be
determined only after the bladder has already

1. Waingankar N etal. Url Oncol, 219;37:572,021-572.e28, 2. Herr HW et al. J Clin Oncol1998:16:1208-1301.

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43. TURBT + Chemo-Immunotherapy Alone for MIBC

HCRN GU16-257'* (Key Eligibility Criteria

+ MIBC
+ cT2-4aNOMO

Gemicis + nivolumab x 4 cycles

|: Cystoscopy + biopsies, urine cytology, MRI |
n=72

Outcomes of Patients
With Clinical CR

|

Time From Registration, mo

= Cystectomy free
Co-primary endpoints: cCR rate and performance of M Local recurrence
NIMC aus cCR in predicting treatment benefit (ie, 2-y MFS if no © Cystectomy

cystectomy and pCR in immediate cystectomy) OS
* Treatment based on patents choice. Ale ni
1. Galsky MD etal ASCO 2021. Abstract 4503, 2. Galsky MD et al. ASCO GU 2023. Abstract 447, 3, Galsky MD et al. Nat Med 2023:29:2825-2834. PeerView.com

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44. Clinical CR Predicted Treatment Benefit!

MFS (Landmark Analysis)

3
3

8 8

8

Log-rank P = .007

Probability of Survival, %
38533
Probability of Survival, %

Log-rank P= 003

OS (Landmark Analysis)

° 70 20 20 0 o

‘Time From Clinical Restaging, mo

Wo, at Rsk No, at Rsk
2 3 10 o

Recor ES

se

20
‘Time From Clinical Restaging, mo

us

30

o

CCR predicted
treatment benefit
with a positive

predict

1. Galsky MD et al, ASCO GU 2023, Abstract 447.2. Galsky MD et al. Nat Med. 2023:29:2825 2854.

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45. Practical Tips for the
Urology/Oncology Practice in 2024

Optimal staging
with pelvic MRI * Optimal clinical response assessment (MRI)

Patient receives
10 +chemoina
clinical trial

> surgery

Outcomes
for the patient

Consider testing the tumor for
biomarkers:

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46. Janice: A Patient With MIBC

« 65-year-old patient presents Panel Discussion
with gross hematuria
+ CT scan unremarkable + How to discuss RC versus

except for thickening of left sparing

lateral wall
+ TURBT revealed T2 MIBC

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47. Progress in the
Advanced Stage

Neal D. Shore, MD, FACS
Medical Director, Carolina Urologic Research Center
Myrtle Beach, South Carolina

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

IMvigor0101

Atezolizumab

Observation

+ Primary endpoint: DFS

+ Key secondary
endpoints: OS, DSS,
distant MFS, NUTRFS

CheckMate -274?

Nivolumab

Placebo

Primary endpoint: DFS
Key secondary
endpoints: OS,
NUTRFS, DSS

Did not meet DFS

PeerView.com/DME827

Met DFS

FDA Approved
August 2021

1. ips Ielnicalrias govstudyiNCTO2450331. 2 tpsleiicatials govstudyINCTO2832408. 3. ntpsIciicatils gowstudyINCTO3244384,

AMBASSADOR?

Coprimary endpoints:
DFS and OS

Key secondary
endpoints: OS and DFS
in PD-L1-positive and
PD-L1-negative patients

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

100: NT jo PD-L1 21%
sa Median DFS (95% Ch, mo pr Median DFS (95% Ci), mo
so wo ERIN

P80 10983152)
HR= 0:71 95% Cl, 0580.88)

Nivolumab

30

Months Me

No at Rsk No at Risk

NvO 353 259 me m7 180 182 13 83 57 49 4 0 NIVO Mo 9888 nn 6 e» 2 2 0
EE E 4 0 poo 2 ms we] zus 2 0

[_ MDFS doubled withnivolumab vs placebo | | mDFS was >6x onger with nivolumab vs placebo, |

1 months; minimum folow-up of 31.8 months.
Lamas,

folow-up 013. 8
1. Galsky MD etal ASCO GU 2023. Abstract PeerView.com

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50. CheckMate -274: Interim OS Data Favored

Nivolumab Versus Placebo in Both Populations’?
IT PD-L1 21%

100- 100-

71.3% Nivolumab

70 mo
60 60.
x x
g 50 gs
40 i 40.
B Median OS (95% Cl), mo N Median OS (95% Cl), mo.
sai , NO 69.5 (58.1-NE) sal NR (NE)
20 i PBO S01(382NE) 20: NR GOONE)
H | ie asx Cn, 078 8-096) | HR (osx cn, 056 026080)
10 : H 10 H
o: —— + + + o + + r
0 6 12 de 24 do de 42 de 64 60 66 72 78 0 6 de de 2 do 36 42 48 94 60
No. at risk Months: No. at risk MURS)
NO 359 326 298 268 244 220 180 150 129 92 60 m 4 0 VOM 17 NS 9 7 2 41 2% M 1 0
PRO 358 308 291 254 226 190 167 136 100 79 586 32 10 0 Peo 142 118 ioe a7 6 46 % 2% 12 2 0

OS folowpis ongoing a he prespecified statistical boundary for significance was not me tie me ofthese analyses. Median (minimum) folowup inthe ITT
popuañon, 36.1 (31.6) months; median (minimum) flow in PO-L1 21% populaben, 23.8 (114) months OS was dened as ème tom date of randomzatn to date of

Seath (fom any cause) i
Y Gay MO et a EAU 2024 PeerView.com

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51. AMBASSADOR: Pembrolizumab Demonstrated DFS Benefit,
But No OS Benefit, at Interim Analysis!

DFS (ITT Population)

No. of Events/Total_ Median (95% Cl), mo
Pembrotzumab 147364
‘Observation 172/348

HR = 0.69 (95% Cl, 0.54-0.87); P= 001

Pembrolizumab

DFS, %

‘Median follow-up (range)
223 mo (0.03-48.9)

08, %

os
No. of Events/Total Median (95% Ci), mo.
Pembrolizumab 1317354 50.9 (438-NR)
= Observation 126/348 55.8 (533-NR)
| HR = 0.98 (95% Cl, 0.76-1.26); P <.884
| Pembrolizumab
«| Observation

Median follow-up (range)
36.9 mo (35.9-37.9)

1. Apolo AB et al ASCO GU 2024. LBAS31.

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52. Potential for Improving Daily Management:
Subcutaneous 10

+ SC administration provides an
alternative with potential benefits for
both patients and providers

+ SC dosing may:
— Alleviate the | need for IV vein ports
re |

Phase 3 Studies Assessing SC IO Across Tumor Types

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

CheckMate -67T45 Under FDA

SC nivolumab in RCC Review
ASCO GU 2024: similar ORR, DCR, and DOR
observed in SC vs IV; SC administration time <5 min

CREST®
Cohort B: SC sasanlimab in NMIBC

RELATIVITY-1277
SC nivolumab + relatlimab (LAG-3)
in metastatic melanoma

1. Buroti M et al, Ann Oncol, 2023:34:693-702. 2. ps cinicatials govstudyiNCTO3735121. 3. hps:ifestwordpharma.convstory/S8 18570.

tps: go pharma.
4. tps linie. govlstuay/NCTO4B10078, 5. George S et al, ASCO GU 2024. Abstract LBAJ60. 6hitps/lnicaltrials povistudyINCTOS 195317.
309,

hips elnicalials govistudyINCTOSE25:

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53. irAEs With Immune Checkpoint Inhibitors
Can Affect Any Organ

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

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54. Immune-Related Adverse Events
Can Occur at Any Time’?

Variable Timing of irAEs
Communicate
With Patients
+ Potential onset of

Colitis Pneumonitis

Endocrinopathy

Toxicity, Grade

Nephritis

Duration of Treatment, wk

1. Marins F et al Nat Rev Cin Oncol. 2019:16863. 2. NCCN Circa Practice Guidelines in Oncology. Management of Inmunotherapy-Relaed Toxctes. Version ñ
12024. ites vin ncen ergiprotessionas/physiian_gs/pdtimmunotherapy pat PeerView.com

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55. Nancy: A Patient With MIBC

56-year-old female athlete, excellent health Panel Discussion
Hematuria off and on for 9 mo; attributes it =

to “runner's hematuria” Would adjuvant IO be
Cystoscopy and imaging consistent appropriate for this patient?
with a sessile mass at the anterior Important patient discussion

bladder wall

Diagnosis of clinically localized MIBC
No neuropathy or hearing loss

CrCL WNL

Treated with 4 cycles of gemcitabine +
cisplatin followed by RC/neobladder
Pathology: T3b, NO (23 LNs removed)

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

Be The BCAN Clinical Trials dashboard can be
BCAN used to find a trial that fits an individual | RESTES
(rey te Rd patient's needs
al Clinical Trials
=o
+ 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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57. Supporting Effective Team-Based Collaboration

Establish dependable relationships
with other specialties and disciplines
(eg, urology, radiation oncology,
pathology, oncologic pharmacy)

Recent Progress and Current

Status of Therapy in mUC
Numerous advances in
therapeutic management of
mUC have occurred over the
last few years

Build solid relationships across
disciplines to optimize patient
experiences and outcomes with
a variety of therapeutic agents

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

Platinum-Based Chemotherapy + Immune Checkpoint Inhibition

+ 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
ha Fe -901)34
Gem/cis + nivolumab (phase 3 CheckMate -901) March 2024

ADC + Immune Checkpoint Inhibition

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

Y Say MO ta Lancet 20203051547 1557 2 Pontes Ye! Loca Oncol 20212293124, 3 van et Hoden N Eg J Ma 202330 178-170,
4. tos ww fda goVIdugs/resourcesinformaton-approved drugs Ida: approves-nivolumab-combinaton-cispati-and gemctabine unesectable-ormeasta
decia $ Podes Tal N Engl Med 202200876008. 8. px nr oa Dodge tomaten aprendio spores aniomab een: —

‘e-pembroizumab local advanced-or metastave-uothelal-cance? PeerView.com

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59. Phase 3 CheckMate -901: Nivolumab Plus Gem/Cis
Improved PFS and OS Versus Gem/Cis Alone‘22

5 a
= iid or ats
Ban Br an

= 702% Games 193304 189147224)

Les HR = 0.78(95% Ci, 0.63-0.96)

ee Fee en
=
ge

» on

ue comics

mers
ErensPuiens sc.

Oran zn 130898)

were 78120

we o7299sc 0590
En

1. tos cinicalrals goustudy/NCTO3036008. 2. van der Hejden MS et al. N Eng! J Med. 2023.380:1778-1780.

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60. Phase 3 CheckMate -901: Nivolumab Plus Gem/Cis
Associated With Deep and Durable Responses"

‘ORR (95% Cl) and BOR per BICR* TTR and DOR
NIVO+GemiCis GemiCis
70 ae coma Any Objective Respoı EN as
60 (51.8-63.2) Pel
en MTTR (Q1-03), mo 212023 212022)
50 3
5 ” Ss MDOR (95% Cl), mo 956-151) 7307.89)
4 11.8 r
is = g ET
E
mTTCR (Q1-03), mo 211922) 211922)
MDOCR (95% CI), mo 37.1 (18.1-NE) 13203184)
so.” 253 283
pois 8 128 + ORR and CR rates were notably higher with NIVO + gemícis
and associated with deep and durable responses
UE, % 16 158 men A
NIVO + GemiCis GomiGis x
(n= 304) (n= 304)

+n al randomized patents. > The most common reasons for UE response Included death before rs tumor assessment withdrawal of consent. treatment stopped due
to tsi, patent never treated, and receip of subsequent antcance’ therapy before fst tumor assessment Based on patients with an objecive response per BICR

(PR or CR as BOR). Based on patents wit a CR per BICR. —

von der Heiden MS et ai N Eng! J Med 2023:289-1778:1789.2. Sonpavde Geta AUA 2024, Abstract POS, PeerView.com

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61. Phase 3 CheckMate -901:
TRAEs in All Treated Patients!

NIVO + Gem/Cis (n = 304) Gem/Cis (n = 288)
Treatment-Related AE, Any Grade Grade 23! Any Grade Grade >:
Any 97 62 93 52
Leading to discontinuation 21 1 17 8
Anemia sr “
fuel a a
Neutropenia A s
Decreased neutrophil covet
Fatigue
Decreased appetite
Decrease platelet count
Decreased whe blend cel cunt
Vomting
ethers

Thrombocytopenia
Prurtus
Constipation
Rash

œ so

* Include events hat occured in treated patents between fst dose and 30 dater las! dose o study therapy. Tomado plot displays individual TRAES occuring at any grade
in 210% of reale patents in ever am. "One grade 5 event occurred in each arm (sepsis in the NIVO + gemicis arm and acute Kidney injury in the gemvcs am). m
Y. van der Heiden MS et a. N Eng! J Med, 202989: 1778-1780 PeerView.com

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62. Phase 3 EV-302: Enfortumab Vedotin Plus Pembrolizumab
Improved OS and PFS Versus Chemo Alone’

08,%
osussessess

* Data cut August 8, 2023; FP: Api 7, 2020; LPI: November 9, 2022. Median survival follow-up: 172 mo. OS at 12 and 18 mo was estimated using Kaplan-Meier
med. PFS at ad 18 mo as estate ang Kaplan met. Cali ig Stated Cox propariona haar model HR favre EV +

‘ponies Tea N'En J Med. 2024300875888 PeerView.com

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63. Phase 3 EV-302: Improved Overall Response’?

Significant improvement in ORR was
observed with EV + pembrolizumab

PR = Confirmed ORR, n (%)

E a mm (5%0C!)
“o di 2-sided P
ee 387 BOR?, n (%)
ES CR
PR
sD
EV+P Chemotherapy PD
MDOR (95% Cl) NR (20.2-NR) 7.0 (6.2-10.2) NE/NAS

* Data euof August 8, 2023. ? BOR according to RECIST v1.1 per BICR. CR or PR was confimed with repeat scans 228 d afer intial response,
Patents had ether pos-baselne assessment and the BOR was determine to be not evaluable per RECIST v1.1 0 no response assessment post baseline

1. Poules T etal 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) (397-492)
<.00001
127 (29.1) 55 (12.5)
169(38.7) 144 (32.0)
82 (18.8) 149 (33.8)
38 (8.7) 60 (13.6)
21 (4.8) 36 (8.2)

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64. Phase 3 EV-302: TRAEs'?

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

veran ]970 958
+ Serious TRAEs
Peripheral Sensory Neuropathy — 122 (27.7%) EV +P
Pas — 85 (19.6%) chemotherapy
Alopecia + TRAES leading to death (per
Maculopapular Rash investigator):
Fatigue = EV+P:4 (0.9%)
a > Asthenia
> Diarthea
Decreased Appetite > Immune-mediated lung disease
Nausea > Multiple organ dysfunction
Anemia syndrome
— Chemotherapy: 4 (0.9%)
son) E > Febrile neutropenia
‘Thrombocytopenia > Myocardial infarction
100 90 80 70 60 50 40 30 20 10 0 10 20 30 40 50 60 70 80 90 100 > Neutropenic sepsis
Incidence, % > Sepsis

* Data cut August 8, 2023. TRAE shown in fu are preter em in 220% of patents for any grade in eer am. :
‘oven Tag RR ‘ PeerView.com

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65. Other ADCs Under Investigation in mUC

Targeting TROP2 Accelerated FDA Approval for
Refractory mUC

+ Sacituzumab govitecan
— Phase 2 TROPHY-U-01: ORR: 28%; DOR: 8.2 months!

— Phase 3 TROPICS-04 underway”

= Accelerated FDA Approval for
Targeting HER2 HER2+ (IHC 3+) Solid Tumors
+ Trastuzumab deruxtecan (T-DXd)?

— Phase 3 DESTINY-PanTumor02*
— Bladder cohort, N = 41 (previously treated); ORR = 39%; 56.3% for HER2 IHC 3+

1. Trodety (sactuzumab govitecan) Presrbing information, hip: www accessdata fa. govidrgsatida_docsabe1202077611 1530350 pa
2 Vuisteke Cet al ASCO GU 2022. Abstract TPSS82. 3, Enheru (vastuzumab derutecan) Prescribing Information. ES
‘nips accessdata da gouérugsatida docslabei 202476 11305028 paf. 4. Me Gemslam Fetal. Cin Oncol 202442:47-58, PeerView.com

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66. Urologists Have a Key Role in Discussing
Genomic Testing With Patients

Eligibility for
FGFR inhibition
requires patients to
undergo testing for
genomic alterations

Testing ideally
occurs at the time
of diagnosis of
metastatic disease

Flatiron database
analysis of >700
eligible patients
showed that fewer
than half had
undergone testing’

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

Options include specifically testing tumors for FGFR3
alterations (eg, RT-PCR companion assay) or more

comprehensive approaches (eg, NGS panels, liquid biopsy)

1. Nimgaonkar Net al. JAMA Oncol 2022:8:1070-1072.

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

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67. NGS Testing!

NGS delivers benefits to patients

Enables early detection of cancer and more accurate
tumor diagnosis. It may enable identification of
mutations for patients in early stages of cancer,
supporting patient screening and monitoring of
residual tumor after initial therapy or surgery

Enables the identification of the best possible
treatment, leading to optimized patient outcomes

Allows for a faster diagnosis as multiple genes can
be sequenced at once

1. hips: spot org publications joumalsvalve-outcomes-spotightos-archies/asueiview/aplan-f-acton-acceleratingpaient-access-o-next- generation:
‘sequencing n-oneolngy accelerating patent access 10 next Jeneraton sequencing moncelogy-a parvo acton,

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NGS delivers benefits to healthcare
systems, payers, and society

Results in improved cancer diagnostic accuracy and
can be cost-effective with an improved QALY per
patient when compared with single-gene testing

Allows multiple genes to be tested at once,
streamlining workflow compared with sequential
single-gene testing and facilitating more timely
results and a shorter time to treatment initiation

Reduces the need for sequential testing and
collection of additional tissue samples (with improved
cost efficiency demonstrated when testing with a
panel instead of locally performing 2-3 single
biomarker tests)

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68. Erdafitinib in FGFR-Altered Metastatic or Unresectable UC

Phase 2 BLC20011%:

©

1. Loriot Yetal N Engl J Med. 2016:381:338-
4. Lovot Tet al. N Engl J Med. 2023:386:166

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DOR, PFS, and OS benefit from

erdafitinib, regardless a

i ohort 1: prior treatment
of FGFR alteration type, tumor ne Central
location, presence of visceral noter Gee screening for
metastases, or prior treatment hen er pao FGFR
with immune checkpoint inhibitor fash ay as Recent fins or

Phase 3 THOR’:

patients with mUC?

Erdafitinib Monotherapy Cohort 1
+ Long-term efficacy outcomes Y Clara n=266
showed that patients derived + Patients with metastatic or

unresectable locally
advanced UC

Cohort 2: no prior treatment
with an anti-PD-L1 agent;
only 1 line of prior systemic
treatment
ECOG PS 0-2

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

Where should FGFR3 inhibitors be integrated into the treatment regimens of

Erdafitinib 8 mg orally
aily for 21 d'in a

Vinflunine g/m
W + docetaxel

Erdafitinib 8 mg orally

once daily fo

Pembrolizumab

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69. Phase 3 THOR: Cohort 1
(Erdafitinib Versus Chemotherapy)?

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

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

x” x
g ¢
o Es
» »
EROA
D —_ °
[EREEELEEEEEEESTET. oT ttt ee eae S S »
Time Since Randomization, mo ‘Time Since Randomization, mo
to ue nus mm es ss 2 22 10 [ue mo we Me 7 3 4 8 à 1: 0
om mm 0 8 9 4 FF 1 1 6 06 0 8

Geno wo 87 6 5 © 1 5 9 8 3 2 2 1 0 0 0 0 0

FDA Approved for Locally Advanced or mUC

With Select FGFR3 Alterations Progressing
on 21 PD-1/PD-L1 Inhibitor

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Median follow-up: 15.9 months.
1: Loris Tet a N Engl J Med. 2023:389:1061-1971

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70. Patients, %

*Mecian follow-up: 15.9 months.

1: Lio T et a N Engl J Med. 2023:389-1961-1971.

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Phase 3 THOR: Cohort 1
(Erdafitinib Versus Chemotherapy)?

ORR: 45.6

40

RR, 3.94 (95% Cl, 2.37-6.57)
P<.001

ORR: 11.5 CR:0.8

(n=1)

Erdafitinib Chemotherapy
(n = 136) (n = 130)

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71. PeerView.com/DME827

Using Erdafitinib Therapy in the Clinic:
Tactics for Safety Management’?

FGFR3 inhibitors are associated with unique AEs

Oral Toxicities Skin and Nail Toxicities

Maintain oral hygiene + Monitor skin and nails
Risk for mucositis and other toxicities + Refer to dermatology and podiatry as needed

Ocular Toxicities

+ Recommended ophthalmologic examinations
— Monthly for first 4 mo; every 3 mo thereafter
= At any time for visual symptoms

; moans + For any occurrence of central serous

+ Dietary phosphate may require restriction retinopathy (CSR)/retinal pigment epithelial detachment

+ Erdafitinib inhibits FGFR signaling in the proximal renal
tubule, impairing function of the sodium-dependent
phosphate co-transporter

= Consult a nutrition professional (eg, registered (RODE
dietitian, nutritionist) for individualized dietary planning sh Repeat ene em
— Consider adding a non-calcium-containing phosphate por da nol ees el ae y

binder (eg, sevelamer carbonate) | — Discontinue permanently for grade 4 CSR/RPED

1. Loot Y eta. N Engl J Med. 2019;381:338-348, 2 Sitker-Radte AO eta. Lancet Oncol 202223:248-258, PeerView.com

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72. Charles: A Patient With mUC

Which 1L regimen
would you choose?

66-year-old presented with hematuria due to

bladder mass Panel Discussion

Urine cytology and TURBT: urothelial

carcinoma How do comorbidities play into treatment
CT CAP: several retroperitoneal selection? .

and pelvic lymph nodes What are important ways urologists and

> medical oncologists can work together up
a to and at this stage?
— Current smoker
— History of grade 2 neuropathy,
no hearing loss
— No autoimmune disease, not on steroids
— No FGFR alterations

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73. Key Takeaways

+ Multiple classes of agents have shown
efficacy across early- and late-stage ®
disease

- Immune checkpoint inhibitors, gene ER

therapy, ADCs, and FGFR inhibitors

- Each approach is associated with + Multidisciplinary care is more
unique indications, modes of important than ever
administration, AE profiles, and + Shared decision-making enables
management strategies patients to engage and find the

right treatment for them

The time is now to have an advanced bladder cancer clini

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