EV-302 / KEYNOTE-A39 Trial

[Slide 1] Abstract #4502, ASCO Annual Meeting 2025 Exploratory analysis of responders from the phase 3 EV-302 trial of enfortumab vedotin plus pembrolizumab (EV+P) VS chemotherapy (chemo) in previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC) Shilpa Gupta, Jens Bedke, Michiel S. Van Der Heijden, Begoña P. Valderrama, Eiji Kikuchi, Jeannie Hoffman-Censits, Gopa lyer, Christof Vulsteke, Steffen Rausch, Se Hoon Park, Alexandra Drakaki, Waddah Arafat, Umang Swami, Ignacio Duran, Jian-Ri Li, Blanca Homet Moreno, Seema R. Gorla, Xuesong Yu, Yi-Tsung Lu, Thomas Powles @neerajaiims --- [Slide 2] Abstract #4502, ASCO Annual Meeting 2025 Exploratory analysis of responders from the phase 3 EV-302 trial of enfortumab vedotin plus pembrolizumab (EV+P) vs chemotherapy (chemo) in previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC) Presenting Author: Shilpa Gupta EV-302 Study Design Arm A Enfortumab vedotin + Treatment until Patient Population N=886 pembrolizumab (EV+P) disease progression, R Previously untreated assessed per RECIST la/mUC 1:1 v1.1 by BICR, Eligible for platinum unacceptable toxicity, Platinum-based chemotherapy CT and for EV+P Arm B or completion of max PD(L)1 naive cycles No maximum treatment cycles for EV+P, maximum 35 cycles of pembrolizumab in Arm A Maximum 6 cycles of gemcitabine and platinum CT in Arm B Efficacy and Safety Endpoints: PRO Endpoints: Dual primary endpoints (PFS by BICR and OS) Key secondary endpoints: Time to pain progression (TTPP), Change from Prespecified secondary endpoints: ORR by BICR, baseline in BPI-SF worst pain at week 26 PFS and ORR per investigator, DOR, DCR, Safety Other pre-specified secondary endpoints: PROs (descriptive with no adjustment for multiplicity) Maintenance therapy could be used following completion and/or discontinuation of platinum chemotherapy BICR, Blinded Independent Central Review BPI-SF, Brief Pain Inventory Short Form; CT, chemotherapy DCR disease control rate DOR, duration of response, EV+P enfortumab vedotin plus pembrolizumab lamUC locally advanced or metastatic urothelial carcinoma, ORR, overall response rate, os, overal survival, PFS, progression free survival, PRO. patient reported outcome, RECIST Response Evaluation Criteria in Solid Tumours Trial design: ESMO 2024 www.clinicaltrials.gov: EV-302 (NCT04223856) @neerajaiims --- [Slide 3] Abstract #4502, ASCO Annual Meeting 2025 Exploratory analysis of responders from the phase 3 EV-302 trial of enfortumab vedotin plus pembrolizumab (EV+P) vs chemotherapy (chemo) in previously untreated locally advanced or metastatic urothelial carcinoma Presenting Author: Shilpa Gupta (la/mUC) Results: Among pts with cCR in the EV+P arm, 38 (28.6%) had upper tract disease and 20 (15%) had liver metastases. Among pts with cCR in the EV+P arm, the median number of cycles was 13 (range, 1-50) for EV and 27 (range, 1-35) for P; median treatment (tx) duration was 22.0 mo (range, 0.7-35.4). Grade >3 TRAEs occurred in 61.7% and 71.9% of pts with cCR in the EV+P and chemo arms, respectively. EV tx-related AESIs and P tx- emergent AEOSI profiles were generally consistent with previous reports. There were no tx-related deaths among pts with cCR. EV+P Chemo cCR: n=133 cCR: n=64 Median PFS, mo (95% CI) NR (NE-NE) 26.9 (16.6-NE) 24-mo PFS rate, % (95% CI) 78.2 (69.8-84.6) 53.7 (40.0-65.5) Median OS, mo (95% CI) NR (39.3-NE) NR (32.1-NE) 24-mo OS rate, % (95% CI) 95.4 (90.0-97.9) 85.8 (74.6-92.4) Median DOCR, mo (95% CI) NR (NE-NE) 15.2 (10.3-NE) 24-mo cCR rate, % (95% CI) 74.3 (65.1-81.4) 43.2 (28.7-56.9) TRAEs leading to dose modification (n, %) - Dose interruption of EV 94 (70.7) - Dose reduction of EV 86 (64.7) - Dose interruption of P 86 (64.7) Conclusion: In the EV+P arm, the proportion of pts achieving cCR was twice that in the chemo arm. Consistent with the ITT data, EV+P reduced the risk of progression or death VS chemo in pts achieving cCR, with appropriate dose modifications. X @neerajaiims

[Slide 1] 7 PFS by BICR Subgroup Analysis: Liver Metastases and Metastatic Disease Site PFS benefit was consistent with the overall population regardless of the presence or absence of liver or visceral metastases 100 Liver Metastases Present HR 100 Liver Metastases Absent HRª 90 (95% CI) 90 (95%CI) 80 0.53 80 0.43 Progression-free survival (%) 70 (0.38-0.76) 50 40 Progression-free survival (%) 70 (0.35-0.52) 60 60 50 40 30 30 20 20 10 10 0 0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 N at risk Time (months) N at risk Time (months) EV+P 100 81 69 57 45 36 29 22 13 9 6 4 1 1 1 1 EV+P 342 328 292 246 208 168 138 110 89 64 39 29 16 5 2 Chemotherapy 99 83 63 42 19 10 9 7 4 2 1 1 1 1 Chemotherapy 345 297 234 171 105 68 47 34 26 17 7 5 4 2 1 1 1 100 HR® 100 Visceral metastases Lymph node only HRª 90 (95%CI) 90 (95% CI) 80 0.45 80 0.40 Progression-free survival (%) 70 (0.37-0.55) 60 Progression-free survival (%) 70 (0.26-0.62) 60 50 50 40 40 30 30 20 20 10 10 0 0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 N at risk Time (months) N at risk Time (months) EV+P 318 287 251 211 170 134 104 81 61 43 24 18 8 2 2 1 EV+P 103 101 90 78 72 62 55 45 38 29 21 15 9 4 1 Chemotherapy 318 264 202 144 76 45 30 21 15 10 4 3 2 1 1 Chemotherapy 104 95 76 52 37 25 22 17 12 8 4 3 3 2 1 1 Data cutoff: 08 August 2023 "Calculated using stratified Cox proportional hazards model; a hazard ratio <1 favors the EV+P arm ASCO Genitourinary #GU24 ASCO AMERICAN SOCIETY OF PRESENTED BY: Michiel S. van der Heijden, MD, PhD CLINICAL ONCOLOGY Cancers Symposium Presentation is property of KNOWLEDGE CONQUERS CANCER --- [Slide 2] 10 OS Subgroup Analysis: Liver Metastases and Metastatic Disease Site OS benefit was consistent with the overall population regardless of the presence or absence of liver or visceral metastases HR HRª 100 Liver Metastases Present (95% CI) 100 Liver Metastases Absent (95%CI) 90 0.47 90 0.47 80 (0.32-0.71) 80 (0.36-0.61) 70 70 Overall survival (%) 60 Overall survival (%) 60 50 50 40 40 30 30 20 20 10 10 0 0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 N at risk Time (months) N at risk Time (months) EV+P 100 91 87 82 76 64 52 42 32 22 16 9 7 5 3 2 EV+P 342 335 322 312 300 267 218 180 150 119 92 58 29 17 9 6 1 1 Chemotherapy 99 95 83 74 58 42 29 23 15 10 9 5 4 3 2 2 1 Chemotherapy 345 328 310 282 259 221 180 141 110 80 51 32 21 15 10 5 5 2 HR HRa 100 Visceral metastases (95%CI) 100 Lymph node only (95%CI) 90 0.47 90 0.46 80 (0.37-0.60) 80 (0.27-0.78) 70 70 Overall survival (%) 60 40 Overall survival (%) 60 50 50 40 30 30 20 20 10 10 0 0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 N at risk Time (months) N at risk Time (months) EV+P 318 303 288 277 261 228 182 147 121 97 71 43 23 15 7 6 1 1 1 EV+P 103 102 100 96 95 87 74 65 53 42 35 23 12 7 5 2 Chemotherapy 318 301 276 244 214 175 134 105 77 55 37 24 13 8 7 4 3 1 1 Chemotherapy 104 101 96 92 83 70 59 44 35 28 20 12 11 9 5 3 3 1 Data cutoff: 08 August 2023 "Calculated using stratified Cox proportional hazards model; a hazard ratio <1 favors the EV+P arm ASCO Genitourinary #GU24 PRESENTED BY: Michiel S. van der Heijden, MD, PhD ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY Cancers Symposium Presentation is property of KNOWLEDGE CONQUERS CANCER --- [Slide 3] 12 Select Subgroups of Objective Response Rate by BICR Objective response rates were ≥60% for EV+P across subgroups; select subgroups shown here Overall Cisplatin eligibility PD-L1 expression Liver metastases Metastatic disease site 80 77.5 67.7 70.8 71.1 70.0 70 63.9 63.3 64.1 60.0 60 53.0 53.4 Percentage (%) 50 44.4 46.6 45.3 41.0 41.4 39.6 40 34.9 30 20 10 0 n/N 296/437 196/441 172/243 123/232 124/194 73/209 114/180 75/183 180/253 118/253 60/100 41/99 236/337 155/342 202/315 126/318 79/102 55/103 Absolute Difference 23.3 (16.8-29.6) 17.8 (9.1-26.2) 29.0 (19.4-38.0) 22.3 (12.1-32.1) 24.5 (16.0-32.6) 18.6 (4.7-31.8) 24.7 (17.4-31.8) 24.5 (16.8-31.9) 24.1 (11.1-36.3) % (95% CI) Low High Visceral Lymph node Overall Eligible Ineligible Present Absent (CPS <10) (CPS >10) metastases only EV+P Chemotherapy Data cutoff: 08 August 2023 ASCO Genitourinary #GU24 PRESENTED BY: Michiel S. van der Heijden, MD, PhD ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY Cancers Symposium Presentation is property of KNOWLEDGE CONQUERS CANCER --- [Slide 4] 11 Subgroup Analysis of OS OS benefit in all pre-specified subgroups was consistent with results in overall population mOS, months (Events/N) mOS, months (Events/N) Subgroup EV+P Chemotherapy Hazard Ratio (95% CI) Subgroup EV+P Chemotherapy Hazard Ratio (95% CI) Overall 31.5 (133/442) 16.1 (226/444) 0.47 (0.38-0.58) Overall 31.5 (133/442) 16.1 (226/444) 0.47 (0.38-0.58) Age Liver metastases <65 years NR (39/144) 19.7 (58/135) 0.46 (0.30-0.71) Present 19.1 (43/100) 10.1 (67/99) 0.47 (0.32-0.71) >65 years 31.5 (94/298) 14.6 (168/309) 0.48 (0.38-0.63) Absent NR (90/342) 17.9 (159/345) 0.47 (0.36-0.61) Race PD-L1 expression White 26.1 (104/308) 15.3 (162/290) 0.47 (0.36-0.60) Low (CPS <10) NR (53/184) 15.5 (99/185) 0.44 (0.31-0.61) Other NR (29/134) 19.3 (64/154) 0.46 (0.29-0.72) High (CPS >10) 31.5 (79/254) 16.6 (125/254) 0.49 (0.37-0.66) Region Cisplatin eligibility North America 25.6 (40/103) 21.2 (42/85) 0.71 (0.44-1.12) Eligible 31.5 (69/244) 18.4 (106/234) 0.53 (0.39-0.72) Europe NR (56/172) 13.9 (110/197) 0.40 (0.28-0.56) Ineligible NR (64/198) 12.7 (120/210) 0.43 (0.31-0.59) Rest of world NR (37/167) 16.4 (74/162) 0.41 (0.27-0.61) Metastatic disease site Sex Visceral metastases 25.6 (108/318) 13.6 (182/318) 0.47 (0.37-0.60) Female 25.4 (32/98) 14.6 (54/108) 0.51 (0.32-0.80) Lymph node only NR (22/103) 27.5 (39/104) 0.46 (0.27-0.78) Male 31.5 (101/344) 16.6 (172/336) 0.47 (0.36-0.60) Renal function ECOG PS Normal 26.1 (24/84) 18.4 (44/95) 0.51 (0.30-0.86) 0 NR (44/223) 18.4 (94/215) 0.36 (0.25-0.53) Mild NR (42/165) 16.4 (78/162) 0.44 (0.30-0.65) 1-2 25.4 (89/219) 13.1 (131/227) 0.54 (0.41-0.72) Moderate/Severe 31.5 (67/193) 13.3 (104/187) 0.50 (0.37-0.69) Primary disease site of origin 0.1 1 5 Upper tract NR (38/135) 18.4 (45/104) 0.53 (0.34-0.83) Lower tract 31.5 (94/305) 15.6 (180/339) 0.46 (0.36-0.59) Favors EV+P Favors chemotherapy 0.1 1 5 Favors EV+P Favors chemotherapy Data cutoff: 08 August 2023 "Renal function categories defined as: Normal (>90 mL/min), Mild (>60 to <90 mL/min), Moderate/Severe (>15 to <60 mL/min) ASCO Genitourinary #GU24 PRESENTED BY: Michiel S. van der Heijden, MD, PhD ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY Cancers Symposium Presentation is property of KNOWLEDGE CONQUERS CANCER

[Slide 1] SATURDAY 5/31 1:15PM rapid orals RCC + BLADDER -Padeliporfin vascular targeted photodynamic therapy in LG UTUC -5yr f/u for KN-564 adjuvant pembro in RCC -Zanza + nivo +/- relatlimab in 1L RCC (STELLAR) -Ipi/nivo on PDIGREE: results from step 1 analysis -Sasanlimab + BCG in NMIBC -Neaodjuvant saci + pembro in MIBC (SURE-02) -Novel nectin-4 ADC + toripalimab in 1L mUC -Pre-op abemaciclib for cisplatin-ineligible MIBC -Axi/nivo VS nivo in TFE/translocation RCC (AREN1721) 5/31 3PM educational session: advancing peri-op tx in MIBC 5/31 4:30PM biomarkers in RCC --- [Slide 2] SUNDAY 6/1 9:45AM orals RCC + BLADDER -Final results from CM-901 -Avelumab + SC VS avelumab maintenance in JAVELIN Bladder Medley -Exploratory analysis of responders in EV-302 -ctDNA in MIBC from NIAGARA -MMC + BCG for NMIBC (ANZUP-1301) -Final analysis of CM-214 -Casdatifan + cabo in previously treated RCC -5-year f/u of phase II LITESPARK-004 (belzutifan) -Phase 1 TRAVERSE study (ALLO-316) 6/1 4:30PM rapid orals PROSTATE -Non-inferiority adjuvant platinum/taxol VS platinum/5FU in high-risk penile CA -Doce + ADT + RT in high-risk PCa -Intensified hormonal blockade with SBRT in PSMA-PET oligomet PCa (Metacure) -Novel B7H3 ADC in mCRPC -Phase 1 Pasritamig (anti-KLK2/CD3 bispecific) in mCRPC -Ipi/nivo +/- SBRT in mCRPC -Exploratory analysis of HRRm by gene subgroup from TALAPRO-2 -Clonal hematopoeisis in mCRPC Lu-617 VS cabazitaxel (TheraP) --- [Slide 3] MONDAY 6/2 9AM posters PROSTATE + RCC + BLADDER 6/2 1:15PM educational session refining tx for patients with metastatic GCT 6/2 3PM new frontiers in PSMA radioligand therapy TUESDAY 6/3 8AM personalizing tx for pts with mCRPC in 2025 6/3 9:45AM oral abstract PROSTATE -CAN-2409 + EBRT in localized PCa -Better treatments + selection in localized PCa -Prognostic significance of PSA>0.2 at 6-12mo in mCSPC -Transcriptome classification of PTEN inactivation to predict cervical from docetaxel at start of ADT for MPC -HRQoL ARANOTE (daro in mCSPC) -ARCHES 5-yr f/u (enza + ADT in mCSPC) -Phase 3 AMPLITUDE: nira + abi in mCSPC with HRRm -Olaparib + radium-223 VS radium-223 in mCRPC with bone metastases -Phase II carbo/cabazi/cetrelimab followed by niraparib +/- cetrelimab in men with aggressive variant PCa

[Slide 1] ASCO Genitourinary Cancers Symposium EV-302: Updated analysis from the phase 3 global study of enfortumab vedotin in combination with pembrolizumab (EV+P) vs chemotherapy (chemo) in previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC) Powles, Michiel S. Van der Heijden,² Yohann Loriot,3 Jens Bedke,4 Begona Pérez Valderrama,⁵ Waddah Gopakumar Arafat, 12 Se Hoon Park, 13 Umang Swami,14 Jian-Ri Li,15 Seema Gorla,¹⁶ Blanca Homet Moreno,¹⁷ Thomas B. yer, Eiji Kikuchi,⁷ Jean Hoffman-Censits,⁸ Christof Vulsteke,⁹ Alexandra Drakaki,¹⁰ Steffen Rausch,¹¹ Xuesong Yu,18 Yi- Tsung Lu,18 Shilpa Gupta London, London, UK: Netherlands Cancer Institute, Amsterdam, the Netherlands: Institut Gustave Roussy, Université Spain: Paris-Saclay, Memorial Barts Cancer Centre, Department Queen Mary of Urology University Eva of Mayr Stin Cancer Center, Kinkum Stutigart, Stuttgart, Germany, Hospital The Universitario Kimmel Virgen Comprehensive del Rocio, Seville, Cancer Center, Johns Villejul France USA St. Marianna University School of Medicine, Kewasaki, Japan, Sidney University, Sloan Kettering Cancer Center Batimore, New MD. York USA: NY, Integrated Cancer Center Ghent, AZ Maria Middelares and Center for Oncological Research Simmons (CORE), Antwerp Comprehensive Cancer Antwerp, Hopkins Medical Center, California, Angeles Medical Center, Los Angeles, CA USA "Eberhard Karts University, Tubingen, Germany, South Korea: Huntsman Center, Belgium University Southwestem of Medical Los Center, Dalas TX USA Samsung Medical Center, Sungiyunkwan University School of Medicine, Seoul, L USA "Merck $ University Cancer institute, of Texas University of tah Sat AKO City, UT, USA "Taichung Veterans General Hospital, Taichung Taiwan Astellas Pharma, Inc. Northbrook, Co. Inc, Rahway, NJ, USA Pizer Inc. Bothel, WA USA The Cleveland Clinic, Cleveland, OH, USA ASCO Genitourinary #GU25 MEMOR Thomas Powles, MD ASCO KNOWLEDGE CONQUERS CANCER Cancers Symposium - your - - - Participate using the ASCO Meetings mobile app or at meetings.asco.org

[Slide 1] ASCO Genitourinary Cancers Symposium Abstract 664 EV-302: Updated analysis from the phase 3 global study of enfortumab vedotin in combination with pembrolizumab (EV+P) vs chemotherapy (chemo) in previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC). #ASCOGU25 I Abstract #664 EV-302: Enfortumab Vedotin + Pembrolizumab (EV+P) vs Chemotherapy in 1L Advanced Urothelial Cancer - Updated Analysis Subgroup os Analysis Cisplatin-eligible: 36.7 vs. 18.7 months (HR: 0.54, 95% CI: 0.42-0.70) Authors: Thomas Powles, Michiel S. Van Der Heijden, Shilpa Gupta, et al. Cisplatin-ineligible: 25.6 vs. 12.7 months (HR: 0.50, 95% CI: 0.39-0.64) Background: Liver metastases present: 19.1 vs. 10.1 months (HR: 0.56, 95% CI: 0.40-0.78) EV-302 / KEYNOTE-A39 demonstrated superior PFS & os with EV+P VS Liver metastases absent: 39.3 vs. 18.3 months (HR: 0.50, 95% CI: 0.40-0.62) chemotherapy in previously untreated locally advanced/metastatic < Safety Profile urothelial carcinoma (la/mUC). Grade ≥3 TRAEs: 57.3% (EV+P) vs. 69.5% (Chemo) EV+P is now the standard of care (SOC) in global treatment guidelines. cCR subgroup Grade ≥3 TRAEs: 61.7% (EV+P) vs. 71.9% (Chemo) Objective: Provide updated efficacy & safety data with 12 months of Treatment-related deaths: 1.1% (EV+P) vs. 0.9% (Chemo) additional follow-up (Median FU: 29.1 months). Conclusion: Key Results (N=886, Data Cutoff: August 8, 2024) EV+P continues to show superior, durable efficacy vs chemotherapy across Efficacy Outcomes all subgroups. Median PFS (BICR): 12.5 vs. 6.3 months (HR: 0.48, 95% CI: 0.41-0.57) No new safety signals identified. Median OS: 33.8 vs. 15.9 months (HR: 0.51, 95% Cl: 0.43-0.61) Confirms EV+P as the SOC for 1L la/mUC. Confirmed ORR (cORR): 67.5% vs. 44.2% Median DOR: 23.3 vs. 7.0 months Complete Response (cCR) Rates EV+P: 30.4% vs. Chemo: 14.5% Median duration of cCR: Not Reached (EV+P) vs. 15.2 months (Chemo) X @nataliagandur @drnataliagandur GANDUR