LITESPARK-022 Trial

[Slide 1] Study Design: LITESPARK-022 (NCT05239728) Median follow-up (data cutoff, Aug 23, 2025): 20 ASCO Genitourinary Key Eligibility Criteria 26 Cancers Symposium 28.4 months (range, 15.0-40.1) Histologically confirmed ccRCC with no prior systemic therapy Surgery <12 weeks prior to randomization Pembrolizumab 400 mg Q6W ECOG PS 0 or 1 N=921 for ~1 year (≤9 cycles) One of the following: + belzutifan 120 mg QD Intermediate-high risk of recurrence (MO): for ≤54 weeks - pT2, grade 4 or sarcomatoid, NO R - pT3, any grade, NO 1:1 High risk of recurrence (MO): Pembrolizumab 400 mg Q6W - pT4, any grade, NO for ~1 year (≤9 cycles) - Any pT, any grade, N+ N=920 + placebo QD M1 NED for <54 weeks Stratification Factors Primary endpoint: DFS by investigator Intermediate-high vs high vs M1 NED Key secondary endpoint: OS Tumor grade 1-2 vs 3-4 Other secondary endpoints include: safety NED, no evidence of disease; QD, daily, Q6W; every six weeks ASCO Genitourinary Cancers Symposium --- [Slide 2] DFS by Investigator, ITT Population 100 91.9% 20 ASCO' Genitourinary 90 HR 0.72 (95% CI, 0.59-0.87) 26 80.7% Cancers Symposium 80 75.8% P = 0.0003* 85.2% 70 73.7% 68.6%; 60 DFS, % 50 Pembrolizumab + Pembrolizumab : 40 belzutifan placebo (N 921) (N 920) 30 Events, (%) 186 (20.2) 246 (26.7) 20 Median, mo 10 12 months 24 months 30 months (95% CI) NR (36.9-NR) NR (NR-NR) 0 0 6 12 18 24 30 36 42 No. at Risk Months Pembrolizumab 921 850 805 669 451 153 35 0 belzutifan Pembrolizumab 920 823 759 619 417 140 38 0 placebo "Denotes statistical significance by stratified log-rank test (p-value boundary, 0.01632). J L NR, not reached ITT population comprised all randomized participants. HRs and 95% CI estimated via stratified Cox proportional hazard model. Median follow-up: 28.4 months (range, 15.0-40.1). Data cutoff: August 23, 2025. " ASCO Genitourinary Cancers Symposium --- [Slide 3] Interim os Results, ITT Population 100 98.3% 96.2% 95.6% 20 98.6% ASCO Genitourinary 90 95.7% 93.8% 26 Cancers Symposium 80 HR 0.78 (95% CI, 0.51-1.19) 70 P 0.1220* 60 Pembrolizumab Pembrolizumab + % 05, 50 belzutifan placebo 40 N 921) (N 920) Events, (%) 38 (4.1) 49 (5.3) 30 Median, mo (95% CI) NR (NR-NR) NR (NR-NR) 20 12 months 87 deaths at IA1: 29% of expected events at final analysis 10 24 months 30 months 0 0 6 12 18 24 30 36 42 No. at Risk Months Pembrolizumab 921 914 900 805 631 319 70 0 + belzutifan Pembrolizumab 920 914 907 807 638 319 69 0 + placebo "Did not reach statistical significance by stratified log-rank test (p-value boundary, 0.00003) Final analysis for OS to occur after approximately 300 os events. HRs and 95% CI estimated via stratified Cox proportional hazard model Median follow-up: 28.4 months (range, 15.0-40.1). Data cutoff: August 23, 2025. ASCO Genitourinary Cancers Symposium --- [Slide 4] Summary of Safety Results, As-Treated Population Pembrolizumab + belzutifana.b Pembrolizumab + placeboa.b 20 ASCO Genitourinary Participants, n (%) (N 915) (N 913) 26 Cancers Symposium Median duration on study therapy, mo (range) 12.4 (0.03-20.1) 12.4 (0.3-18.9) Treatment-emergent AEs 905 (98.9) 863 (94.5) Grade >3 477 (52.1) 276 (30.2) Led to discontinuation of all study treatment 109 (11.9) 82 (9.0) Led to death 10 (1.1) 11 (1.2) Serious 270 (29.5) 182 (19.9) Serious and led to discontinuation of all study 59 (6.4) 43 (4.7) treatment Treatment-related AEs 884 (96.6) 737 (80.7) Grade >3 386 (42.2) 163 (17.9) Led to discontinuation of all study treatment 93 (10.2) 67 (7.3) Led to death 3 (0.3) 3 (0.3) Immune-mediated AEs or infusion reactions 324 (35.4) 353 (38.7) Grade >3 86 (9.4) 76 (8.3) "Median number of pembrolizumab cycles was 9 (range 1-9) for both arms. Median dose intensity (range) was 107.3 mg/day (8.3-120.) 0) for belzutifan (89 4% of planned starting dose) and 119 5 mg/day (54 1- 141.2) for placebo (99. 6% of planned starting dose). "Serious adverse events were defined as any adverse event that resulted in death, was life-threatening required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability or incapacity, was a congenital anomaly or birth defect, or was judged by the investigator to be a serious adverse event Safety was assessed in all participants who received at dose of study treatment. Data cutoff: August 23, 2025 ASCO Genitourinary Cancers Symposium

[Slide 1] Study Design: LITESPARK-022 (NCT05239728) Median follow-up (data cutoff, Aug 23, 2025): Key Eligibility Criteria 28.4 months (range, 15.0-40.1) Histologically confirmed ccRCC with no prior systemic therapy Surgery ≤12 weeks prior to randomization Pembrolizumab 400 mg Q6W ECOG PS 0 or 1 N = 921 for ~1 year (≤9 cycles) One of the following: + belzutifan 120 mg QD Intermediate-high risk of recurrence (MO): for ≤54 weeks - pT2, grade 4 or sarcomatoid, NO R - pT3, any grade, NO 1:1 High risk of recurrence (MO): Pembrolizumab 400 mg Q6W — pT4, any grade, NO for ~1 year (≤9 cycles) - Any pT, any grade, N+ N = 920 + placebo QD M1 NED for ≤54 weeks Stratification Factors Primary endpoint: DFS by investigator Intermediate-high VS high VS M1 NED Key secondary endpoint: OS Tumor grade 1-2 VS 3-4 Other secondary endpoints include: safety NED, no evidence of disease; QD, daily; Q6W; every six weeks. --- [Slide 2] DFS by Investigator, ITT Population 100 91.9% 90 HR 0.72 (95% CI, 0.59-0.87) 80.7% 80 85.2% 75.8% P = 0.0003* 70 73.7% 68.6% 60 DFS, % 50 Pembrolizumab + Pembrolizumab + 40 belzutifan placebo (N 921) (N 920) 30 Events, n (%) 186 (20.2) 246 (26.7) 20 Median, mo 10 12 months 24 months 30 months (95% CI) NR (36.9-NR) NR (NR-NR) 0 0 6 12 18 24 30 36 42 No. at Risk Months Pembrolizumab 921 850 805 669 451 153 35 0 + belzutifan Pembrolizumab 920 823 759 619 417 140 38 0 + placebo *Denotes statistical significance by stratified log-rank test (p-value boundary, 0.01632). NR, not reached. ITT population comprised all randomized participants. HRs and 95% CI estimated via stratified Cox proportional hazard model. Median follow-up: 28.4 months (range, 15.0-40.1). Data cutoff: August 23, 2025. --- [Slide 3] Interim OS Results, ITT Population 100 98.3% 96.2% 95.6% 98.6% 90 95.7% 93.8% 80 HR 0.78 (95% CI, 0.51-1.19) 70 P = 0.1220* 60 OS, % Pembrolizumab + Pembrolizumab + 50 belzutifan placebo 40 (N 921) (N 920) Events, n (%) 38 (4.1) 49 (5.3) 30 Median, mo (95% CI) NR (NR-NR) NR (NR-NR) 20 87 deaths at IA1: 29% of expected events at final analysis 10 12 months 24 months 30 months 0 0 6 12 18 24 30 36 42 No. at Risk Months Pembrolizumab 921 914 900 805 631 319 70 0 + belzutifan Pembrolizumab 920 914 907 807 638 319 69 0 + placebo "Did not reach statistical significance by stratified log-rank test (p-value boundary, 0.00003). Final analysis for OS to occur after approximately 300 OS events. HRs and 95% CI estimated via stratified Cox proportional hazard model. Median follow-up: 28.4 months (range, 15.0-40.1). Data cutoff: August 23, 2025. --- [Slide 4] Treatment-Emergent AEs with Incidence ≥10%, As-Treated Population Pembrolizumab + belzutifan Pembrolizumab + placebo Anemia 84.0% 11.4% Fatigue 36.4% 26.3% Alanine aminotransferase increased 28.9% 14.1% Aspartate aminotransferase increased 22.0% 11.9% Diarrhea 20.9% 16.2% Pruritus 20.3% 23.5% Dizziness 19.3% 8.2% Headache 16.9% 10.8% Nausea 16.3% 12.2% Arthralgia 15.1% 16.9% Hypothyroidism 14.9% 18.8% Asthenia 12.9% 7.4% Rash 12.3% 15.4% Blood creatinine increased 12.0% 12.3% Dyspnea 10.7% 4.4% Hyperthyroidism 7.7% 11.4% Cough 7.5% 10.2% 100 80 60 40 20 0 20 40 60 80 100 Incidence, % Any grade AEs Grade ≥3 AEs Any grade AEs Grade ≥3 AEs Data cutoff: August 23, 2025.

[Slide 1] ASCO Genitourinary Cancers Symposium Adjuvant Pembrolizumab Plus Belzutifan Versus Pembrolizumab for Clear Cell Renal Cell Carcinoma: The Randomized Phase 3 LITESPARK-022 Study Toni K. Choueiri1, Robert J. Motzer², Jose A. Karam³, Dingwei Ye4, Zhisong He⁵, Christian Caglevic⁶, Wesley Yip7, Cristina Suárez⁸, Tom Ferguson⁹, Yen-Hwa Chang¹⁰, Carlos Rojas¹¹, Roberto lacovelli12, Yuksel Ürün¹³, Elena Verzoni1⁴, Juan Carlos Vázquez Limón¹⁵, Camillo Porta¹⁶, Robert G. Uzzo¹⁷, Jae Lyun Lee¹⁸, Balaji Venugopal19,20, Rana R. McKay21, Hans Hammers²², Hideaki Miyake23, Jad Chahoud²⁴, Hong Liu25, Joseph E. Burgents²⁵, Manish Sharma25, Thomas B. Powles26 'Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Memorial Sloan Kettering Cancer Center, New York, NY, USA; University of Texas MD Anderson Cancer Center, Houston, TX, USA; Fudan University Shanghai Cancer Center, Shanghai, China; Peking University First Hospital, Beijing, China; Centro de Investigación e Innovación en Cancer- Fundación Arturo López Pérez, Santiago, Chile; City of Hope Comprehensive Cancer Center, Duarte, CA, USA; Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; Fiona Stanley Hospital, Perth, WA, Australia; 10Taipei Veterans General Hospital, Taipei City, Taiwan; 1Bradford Hill Investigación Clinica and Universidad Finis Terrae, Santiago, Chile; Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Ankara University Medical Faculty, Ankara, Türkiye: "Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1, Milan, Italy; 15Servicio de Oncologia Hospital Civil de Guadalajara, "Fray Antonio Alcalde", Universidad de Guadalajara, Jalisco, México; Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari and University of Bari "A. Moro," Bari, Italy; 17Fox Chase Comprehensive Cancer Center, Philadelphia, USA; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; "Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom; University of Glasgow, Glasgow, United Kingdom; 21University of California San Diego, San Diego, CA, USA; 22University of Texas Southwestern Medical Center, Dallas, TX, USA; 23Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan; "Orlando Health Cancer Institute, Orlando, FL, USA; 25Merck & Co., Inc., Rahway, NJ, USA; 26Barts Cancer Institute NIHR Biomedical Research Centre, and Queen Mary University of London, London, United Kingdom ASCO Genitourinary Toni K. Choueiri #GU26 ASCO AMERICAN SOCIETY OF PRESENTED BY: CLINICAL ONCOLOGY Cancers Symposium Presentation property of be author and ASCO Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER Γ ASCO Genitourinary Cancers Symposium --- [Slide 2] Study Design: LITESPARK-022 (NCT05239728) Median follow-up (data cutoff, Aug 23, 2025): 20 ASCO Genitourinary Key Eligibility Criteria 26 Cancers Symposium 28.4 months (range, 15.0-40.1) Histologically confirmed ccRCC with no prior systemic therapy Surgery <12 weeks prior to randomization Pembrolizumab 400 mg Q6W ECOG PS 0 or 1 N = 921 for ~1 year (≤9 cycles) One of the following: + belzutifan 120 mg QD Intermediate-high risk of recurrence (MO): for ≤54 weeks - pT2, grade 4 or sarcomatoid, NO R - pT3, any grade, NO 1:1 High risk of recurrence (MO): Pembrolizumab 400 mg Q6W - pT4, any grade, NO for ~1 year (≤9 cycles) - Any pT, any grade, N+ N=920 + placebo QD M1 NED for ≤54 weeks Stratification Factors Primary endpoint: DFS by investigator Intermediate-high vs high vs M1 NED Key secondary endpoint: OS Tumor grade 1-2 VS 3-4 Other secondary endpoints include: safety NED, no evidence of disease; QD, daily; Q6W; every six weeks. ASCO Genitourinary Cancers Symposium --- [Slide 3] DFS by Investigator, ITT Population 100 91.9% 20 ASCO*Genitourinary 90 HR 0.72 (95% CI, 0.59-0.87) 80.7% 26 Cancers Symposium 80 85.2% 75.8% P = 0.0003* 70 73.7% 68.6%; 60 DFS, % 50 Pembrolizumab + Pembrolizumab + 40 belzutifan placebo (N 921) (N 920) 30 Events, (%) 186 (20.2) 246 (26.7) 20 Median, mo 10 12 months 24 months 30 months (95% CI) NR (36.9-NR) NR (NR-NR) 0 0 6 12 18 24 30 36 42 No. at Risk Months Pembrolizumab 921 850 805 669 451 153 35 0 + belzutifan Pembrolizumab 920 823 759 619 417 140 38 0 + placebo "Denotes statistical significance by stratified log-rank test (p-value boundary, 0.01632). NR, not reached ITT population comprised all randomized participants. HRs and 95% CI estimated via stratified Cox proportional hazard model. Median follow-up: 28.4 months (range, 15.0-40.1). Data cutoff: August 23, 2025. ASCO Genitourinary Cancers Symposium --- [Slide 4] Interim OS Results, ITT Population 100 98.3% 96.2% 95.6% 20 98.6% ASCO Genitourinary 90 95.7% 93.8% 26 Cancers Symposium 80 HR 0.78 (95% CI, 0.51-1.19) 70 P = 0.1220* 60 % 05, Pembrolizumab Pembrolizumab 50 belzutifan placebo 40 (N 921) (N 920) Events, n (%) 38 (4.1) 49 (5.3) 30 Median, mo (95% CI) NR (NR-NR) NR (NR-NR) 20 12 months 24 months 30 months 87 deaths at IA1: 29% of expected events at final analysis 10 0 0 6 12 18 24 30 36 42 No. at Risk Months Pembrolizumab 921 914 900 805 631 319 70 0 + belzutifan Pembrolizumab 920 914 907 807 638 319 69 0 + placebo "Did not reach statistical significance by stratified log-rank test (p-value boundary. 0.00003). Final analysis for OS to occur after approximately 300 OS events. HRs and 95% CI estimated via stratified Cox proportional hazard model. Median follow-up: 28.4 months (range, 15.0-40.1) Data cutoff: August 23, 2025. ASCO Genitour

[Slide 1] ASCO Genitourinary Cancers Symposium Adjuvant Pembrolizumab Plus Belzutifan Versus Pembrolizumab for Clear Cell Renal Cell Carcinoma: The Randomized Phase 3 LITESPARK-022 Study Toni K. Choueiri1, Robert J. Motzer², Jose A. Karam³, Dingwei Ye4, Zhisong He⁵, Christian Caglevic⁶, Wesley Yip7, Cristina Suárez⁸, Tom Ferguson⁹, Yen-Hwa Chang¹⁰, Carlos Rojas¹¹, Roberto lacovelli12, Yuksel Ürün¹³, Elena Verzoni1⁴, Juan Carlos Vázquez Limón15, Camillo Porta¹⁶, Robert G. Uzzo17, Jae Lyun Lee¹⁸, Balaji Venugopal19.20, Rana R. McKay21, Hans Hammers²², Hideaki Miyake²³, Jad Chahoud²⁴, Hong Liu²⁵, Joseph E. Burgents²⁵, Manish Sharma²⁵, Thomas B. Powles26 Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Memorial Sloan Kettering Cancer Center, New York, NY, USA; University of Texas MD Anderson Cancer Fundación Arturo López Pérez, Santiago, Chile; City of Hope Comprehensive Cancer Center, Duarte, CA, USA; "Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Vall Center, Houston, TX, USA; Fudan University Shanghai Cancer Center, Shanghai, China: Peking University First Hospital, Beijing, China; Centro de Investigación . Innovación en Cáncer- Clínica d'Hebron and Universidad Finis Terrae, Santiago, Chile; Fondazione Policiinico Universitario Agostino Gemelli RCCS, Rome, Italy, 13Ankara University Medical Faculty, Ankara, Türkiye: Barcelona Hospital Campus, Barcelona, Spain; Fiona Stanley Hospital, Perth, WA, Australia; Taipei Veterans General Hospital, Taipei City, Taiwan; Bradford Hill Investigación Universidad de Guadalajara, Jalisco, México; Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari and University of Ban A Moro, Bari, Italy, "Fax Chase Comprehensive United "Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1, Milan, Italy: Servicio de Oncología Hospital Civil de Guadalajara, Fray Antonio Alcaide", University University Graduate School of Medicine, Kobe, Hyogo, Japan; Orlando Health Cancer Institute, Orlando, FL, USA; 25Merck & Co., Inc., Rahway, NJ, USA; "Barts Cancer Cancer Center, of Glasgow, Glasgow, United Kingdom; University of California San Diego, San Diego, CA, USA; University of Texas Southwestern Medical Center, Dallas, TX, Institute USA; NIHR 21Kobe Philadelphia, USA; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; Beatson West of Scotland Cancer Centre, Glasgow, Kingdom; Biomedical Research Centre, and Queen Mary University of London, London, United Kingdom PRESENTED ST. Toni K. Chouein ASCO AMERICAN CHECKOOF ASCO Genitourinary #GU26 ENDWLEDGE CONQUERS CANCER Cancers Symposium Presentation esperty the author and ASCO Permission required by MM contact permissions@wice.org 20 ASCO*Genitourinary --- [Slide 2] Study Design: LITESPARK-022 (NCT05239728) Median follow-up (data cutoff, Aug 23, 2025): Key Eligibility Criteria 28.4 months (range, 15.0-40.1) Histologically confirmed ccRCC with no prior systemic therapy Surgery <12 weeks prior to randomization Pembrolizumab 400 mg Q6W ECOG PS 0 or 1 N = 921 for ~1 year (59 cycles) One of the following: + belzutifan 120 mg QD Intermediate-high risk of recurrence (MO): for ≤54 weeks - pT2, grade 4 or sarcomatoid, NO R - pT3, any grade, NO 1:1 High risk of recurrence (MO): Pembrolizumab 400 mg Q6W - pT4, any grade, NO for ~1 year (≤9 cycles) - Any pT, any grade, N+ N = 920 + placebo QD M1 NED for ≤54 weeks Stratification Factors Primary endpoint: DFS by investigator Intermediate-high VS high VS M1 NED Key secondary endpoint: OS Tumor grade 1-2 VS 3-4 Other secondary endpoints include: safety NED, no evidence of disease; QD, daily; Q6W; every six weeks. --- [Slide 3] DFS by Investigator, ITT Population 100 91.9% 90 80.7% HR 0.72 (95% CI, 0.59-0.87) 80 85.2% 75.8% P = 0.0003* 70 73.7% 68.6%; 60 DFS, % 50 Pembrolizumab + Pembrolizumab + 40 belzutifan placebo (N 921) (N 920) 30 Events, n (%) 186 (20.2) 246 (26.7) 20 Median, mo 10 12 months 24 months 30 months (95% CI) NR (36.9-NR) NR (NR-NR) 0 0 6 12 18 24 30 36 42 No. at Risk Months Pembrolizumab 921 850 805 669 451 153 35 0 + belzutifan Pembrolizumab 920 823 759 619 417 140 38 0 + placebo "Denotes statistical significance by stratified log-rank test (p-value boundary, 0.01632). NR, not reached. ITT population comprised all randomized participants. HRs and 95% CI estimated via stratified Cox proportional hazard model. Median follow-up: 28.4 months (range, 15.0-40.1). Data cutoff: August 23, 2025. --- [Slide 4] Summary and Conclusions Pembrolizumab + belzutifan showed a statistically significant and clinically meaningful DFS improvement VS pembrolizumab monotherapy in participants with ccRCC at increased risk of recurrence post nephrectomy - DFS benefit was generally consistent across prespecified subgroups Additional follow-up is planned for the key secondary endpoint of OS The safety profile of pembrolizumab + belzutifan was manageable with a low rate of AEs leading to the discontinuation of both study drugs - Overall safety was consistent with the expected profiles of each individual drug LITESPARK-022 is the first adjuvant phase 3 trial in RCC to show a significant benefit for a combination treatment VS an active immunotherapy comparator These results support the addition of belzutifan to standard-of-care adjuvant pembrolizumab for patients with ccRCC at increased risk of recurrence

[Slide 1] The ASCO® Post EVENING NEWS Monday, March 16, 2026 TODAY IN ONCOLOGY Adjuvant Pembrolizumab Plus Belzutifan for Patients With RCC at Increased Risk of Recurrence Based on results from the phase III KEYNOTE-564 study, adjuvant pembrolizumab is currently a standard of care for patients with clear cell renal cell carcinoma (RCC) who have an increased risk of recurrence following a nephrectomy. Now, results from the phase III LITESPARK-022 study investigating the combination of adjuvant pembrolizumab plus the oral HIF-2a inhibitor belzutifan in high-risk patients show that the regimen demonstrated a statistically significant improvement in disease-free survival vs pembrolizumab plus placebo.