KEYNOTE-564 Trial

ASCO 2026 RCC May Simply Be a Poor ctDNA-Shedding Tumor. ONE CORE TAKEAWAY MV ONCO KEYNOTE-564 ctDNA ANALYSIS In the adjuvant setting, current ctDNA assays identified <15% of future recurrences before clinical relapse. Therefore, ctDNA negativity may be poorly reassuring. However, ctDNA positivity retains strong prognostic value and marks biologically higher-risk disease. Baseline ctDNA Strong prognostic positivity: ~5-8% specificity, limited sensitivity Choueiri et al ASCO 2026

A Disease-free Survival in the Intention-to-Treat Population 12 Mo 24 Mo 36 Mo 48 Mo 100 A larger share of DFS events 85.5 occurred after the first year 90 with Pembrolizumab 78.2 80 72.4 By 48 months (latest follow-up), the Steeper early cumulative proportion of events that decline in the 70 64.9 occurred within the first year is: Placebo arm Percentage of Participants 76.1 Pembrolizumab: ~41% 60 67.2 Placebo: ~55% More DFS events occur earlier in 50 62.9 56:6 the first year 40 Pembrolizumab with Placebo. Placebo 30 20 First 12 months 10 (the first year) 0 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 Months No. at Risk Pembrolizumab 496 458 416 388 370 355 337 327 307 284 221 160 65 19 5 0 Placebo 498 438 390 357 333 320 307 292 282 254 210 139 62 16 2 0 Percent of all DFS events observed so far that occurred within the first year (up to 12 months) Placebo Fewer early events Pembrolizumab with Pembrolizumab; Events within first year = 1- DFS at 12 mo = 1 - 0.761 = 0.239 (23.9%) Events within first year = 1- DFS at 12 mo = 1- 0.855 = 0.145 (14.5%) more events occur Total events to date = 1- DFS at 48 mo = 1- 0.566 = 0.434 (43.4%) Total events to date = 1- DFS at 48 mo = 1- 0.649 = 0.351 (35.1%) later (after year 1). Percentage within first year = 0.239 / 0.434 = 0.551 ≈ 55% Percentage within first year = 0.145 / 0.351 = 0.413 ≈ 41%

ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY KNOWLEDGE CONQUERS CANCER ASCO Annual Meeting Abstract #: 4502 Oral Abstract Session ctDNA analysis in participants with renal cell carcinoma treated with adjuvant pembrolizumab or placebo in the KEYNOTE-564 trial. Authors: Toni K. Choueiri, Piotr Tomczak, Naomi B. Haas, David F. McDermott, Balaji Venugopal, Se Hoon Park, Thomas Ferguson, Stefan N. Symeonides, Wayne Yen Hwa Chang, Jae Lyun Lee, Naveed Sarwar, Piotr Sawrycki, Chen-Hua Chuang, Yiwei Zhang, Razvan Cristescu, Cai Chen, Carol E. Pena, Rodolfo F. Perini, Joseph E. Burgents, Thomas Powles Organizations: Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, Poznan University of Medical Sciences, Poznan, Poland, Abramson Cancer Center at the University of Pennsylvania, Philadelphia, PA, Beth Israel Deaconess Medical Center, Boston, MA, Beatson West of Scotland Cancer Centre and University of Glasgow, Glasgow, United Kingdom, Sungkyunkwan University, Samsung Medical Center, Seoul, South Korea, Department of Medical Oncology, Fiona Stanley Hospital, Perth, Western Australia, Australia, Edinburgh ECMC, Edinburgh Cancer Centre and University of Edinburgh, Edinburgh, United Kingdom, Taipei Veterans General Hospital, Taipei, Taiwan, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea, Imperial College Healthcare NHS Trust, London, United Kingdom, Provincial Hospital in Torun, Torun, Poland, Merck & Co., Inc., Rahway, NJ, Barts Health NHS Trust and the Royal Free NHS Foundation Trust, Barts Cancer Institute, and Queen Mary University of London, London, United Kingdom Background: In the phase 3 KEYNOTE-564 trial (NCT03142334), adjuvant pembrolizumab (pembro) was superior to placebo (pbo) in participants (pts) with clear cell renal cell carcinoma (ccRCC) at increased risk of recurrence post nephrectomy. We report an analysis of pretreatment and on- treatment ctDNA (using 2 versions of a ctDNA assay with different sensitivities) with clinical outcomes in KEYNOTE-564.

Abstract #4502, ASCO Annual Meeting 2026 ctDNA analysis in participants with renal cell carcinoma treated with adjuvant pembrolizumab or placebo in the KEYNOTE-564 trial Toni K. Choueiri, Piotr Tomczak, Naomi B. Haas, David F. McDermott, Balaji Venugopal, Se Hoon Park, Thomas Ferguson, Stefan N. Symeonides, Wayne Yen Hwa Chang, Jae Lyun Lee, Naveed Sarwar, Piotr Sawrycki, Chen-Hua Chuang, Yiwei Zhang, Razvan Cristescu, Cai Chen, Carol E. Pena, Rodolfo F. Perini, Joseph E. Burgents, Thomas Powles @neerajaiims --- Abstract #4502, ASCO Annual Meeting 2026 ctDNA analysis in participants with renal cell carcinoma treated with adjuvant pembrolizumab or placebo in the KEYNOTE-564 trial Presenting Author: Toni Choueiri Median follow-up to data cutoff (Sept 25, 2024): Key Eligibility Criteria 69.5 months (range, 60.2-86.9) Histologically confirmed clear cell RCC with no prior systemic therapy Surgery <12 weeks prior to randomization N = 496 Postnephrectomy intermediate-high risk of recurrence (MO): Pembrolizumab 200 mg Q3W - pT2, grade 4 or sarcomatoid, NO for ~1 year (≤17 cycles) R - pT3, any grade, NO 1:1 Postnephrectomy high risk of recurrence (MO): Placebo Q3W - pT4, any grade, NO N = 498 for ~1 year (≤17 cycles) - Any pT, any grade, N+ Postnephrectomy + complete resection of metastasis (M1 NED) ECOG PS 0 or 1 Stratification Factors Primary Endpoint M stage (MO VS. M1 NED) Disease-free survival (DFS) by investigator MO group further stratified: Key Secondary Endpoint ECOG PS 0 VS. 1 Overall survival (OS) US VS. non-US Other Secondary Endpoints Safety www.clinicaltrials.gov: NCT03142334 X @neerajaiims --- Abstract #4502, ASCO Annual Meeting 2026 ctDNA analysis in participants with renal cell carcinoma treated with adjuvant pembrolizumab or placebo in the KEYNOTE-564 trial Presenting Author: Toni Choueiri Methods: ctDNA was evaluated using Natera's Signatera RUO tissue-exome-based 16-plex and 64-plex ctDNA assays. Primary objectives of this analysis were to evaluate the association of baseline ctDNA status and ctDNA status change from baseline to cycle 5 day 1 (C5D1) with disease-free survival (DFS). Significance was prespecified at multiplicity-adjusted a = 0.05. Sensitivity (percentage of ctDNA-positive pts among all pts with a DFS event) and specificity (percentage of ctDNA-negative pts among all pts without a DFS event) to predict DFS were also evaluated. Results: 994 pts were randomized to pembro (n = 496) or pbo (n = 498). ctDNA samples from 736 pts (pembro n = 374; pbo n = 362) were analyzed at baseline and from 641 pts at C5D1 (pembro n = 314; pbo n = 327) using both assays. In both treatment arms, ctDNA was detectable at baseline in 40 pts (5.4%) using the 16-plex assay and 60 pts (8.2%) using the 64-plex assay. By risk group, using the 16-plex assay, ctDNA was detectable at baseline in 26 of 642 (4.0%) intermediate-high risk pts, 10 of 53 (18.9%) high-risk pts, and 4 of 38 (10.5%) M1 NED pts; using the 64-plex assay, ctDNA was detectable in 44 of 642 (6.9%) intermediate-high risk pts, 11 of 53 (20.8%) high-risk pts, and 5 of 38 (13.2%) M1 NED pts. For both assays, ctDNA positivity was negatively associated with DFS in both pembro and pbo arms (P's < 0.05). Pembro Pembro Pbo Pbo % (n/N) Sensitivity Specificity Sensitivity Specificity Baseline ctDNA, 16-12 (17/146) 98 (224/228) 10 (18/173) 99 (188/189) plex Baseline ctDNA,64- 15 (22/146) 96 (220/228) 15 (26/173) 98. 185/189) plex Conclusion: While sensitivity was low, ctDNA positivity was associated with worse DFS outcomes irrespective of the ctDNA assay used. ctDNA clearance was higher in the pembro arm than the placebo arm. These data highlight the limitations of these ctDNA assays in ccRCC. @neerajaiims

The NEW ENGLAND JOURNAL of MEDICINE ESTABLISHED IN 1812 APRIL 18, 2024 VOL. 390 NO. 15 Overall Survival with Adjuvant Pembrolizumab in Renal-Cell Carcinoma T.K. Choueiri, P. Tomczak, S.H. Park, B. Venugopal, T. Ferguson, S.N. Symeonides, J. Hajek, Y.-H. Chang, J.-L. Lee, N. Sarwar, N.B. Haas, H. Gurney, P. Sawrycki, M. Mahave, M. Gross-Goupil, T. Zhang, J.M. Burke, G. Doshi, B. Melichar, E. Kopyltsov, A. Alva, S. Oudard, D. Topart, H. Hammers, H. Kitamura, D.F. McDermott, A. Silva, E. Winquist, J. Cornell, A. Elfiky, J.E. Burgents, R.F. Perini, and T. Powles, for the KEYNOTE-564 Investigators*

KEYNOTE-564 (NCT03142334) Study Design Key Eligibility Criteria Histologically confirmed clear cell renal cell carcinoma N = 496 Pembrolizumab 200 mg Intermediate-high risk: pT2, grade 4 or sarcomatoid, Q3W NO, MO; pT3, any grade, NO, MO for ~1 yearb High risk: pT4, any grade, NO, MO; any pT, any R grade, N+, MO (1:1) M1 no evidence of disease (NED) after surgeryᵃ Surgery ≤12 weeks prior to randomization Placebo No prior systemic therapy Q3W N = 498 ECOG PS 0 or 1 for ~1 yearb Tissue sample for PD-L1 assessment Stratification Factors Metastatic status (MO vs M1 NED) Primary endpoint: DFS per investigator MO group further stratified: Key secondary endpoint: os ECOG PS 0 vs 1 Other secondary endpoints: Safety US vs non-US Median (range) time from randomization to cutoff: 30.1 (20.8-47.5) months Q3W, every 3 weeks M1 NED: no evidence of disease after primary tumor soft tissue metastases completely resected $1 year from nephrectomy; $17 cycles of treatment were equivalent to -1 year. Data cutoff date: June 14, 2021. --- Updated DFS by Investigator, ITT Population Pembro Placebo (N = 496) (N = 498) 100 Events, n 188 241 90 Median, mo (95% CI) NR (NR-NR) 68.3 (51.7-NR) 78.2% 80 Median follow-up was 69.5 months (range, 60.2-86.9) 72.5% 70 65.0% 60.9% 67.2% 58.5% 60 62.8% DFS, * 56.5% 50 Pembrolizumab 52.2% 48.7% 40 Placebo 30 HR 0.71 (95% CI 0.59-0.86) 20 10 24 months 36 months 48 months 09 months 72 months 0 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 No. at Risk Months NR, not reported Pembrolizumab 496 459 417 388 371 356 338 328 309 291 282 269 207 128 88 63 26 1 0 Primary OFS endpoint was met at A1 and was not formally statistically tested thereafter Placebo 498 438 390 357 334 322 308 293 283 260 251 240 179 118 71 55 21 1 0 Data $ cutoff date: September 25, 2024 --- Updated OS, ITT Population Pembro Placebo (N = 496) (N = 498) Events, n 68 99 Median, mo (95% CI) NR (NR-NR) NR (NR-NR) 100 96.3% 93.9% 91.2% Median follow-up was 69.5 months (range, 60.2-86.9) 90 93.9% 87.7% 86.1% 89.5% 80 86.0% 82.3% 79.4% 70 60 OS, % 50 Pembrolizumab 40 Placebo 30 HR 0.66 (95% CI 0.48-0.90) 20 10 24 months 36 months 48 months 60 months 72 months 0 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 No. at Risk Months Key secondary OS endpoint was met at IA3 and Pembrolizumab 496 489 486 484 479 470 468 462 452 445 442 436 426 310 198 121 50 3 0 was not formally statistically tested thereafter. Placebo 498 494 487 483 476 463 455 441 433 423 419 413 400 284 177 111 46 4 0 Data cutoff date: September 25, 2024. --- DFS by Subgroups Events/Participants Hazard Ratio (95% CI) Overall 429/994 0.71 (0.59-0.86) Age <65 yrs 271/664 0.78 (0.61-0.99) >65 yrs 158/330 0.65 (0.47-0.89) Sex Female 118/288 0.64 (0.45-0.93) Male 311/706 0.76 (0.61-0.95) ECOG performance status 0 360/847 0.72 (0.58-0.88) 1 69/147 0.75 (0.47-1.21) PD-L1 status CPS <1 83/237 0.86 (0.56-1.32) CPS ≥1 341/748 0.69 (0.55-0.85) Regions United States 101/231 0.71 (0.48-1.05) Outside United States 328/763 0.73 (0.59-0.91) Tumor grade 1-2 116/338 0.79 (0.55-1.14) 3 185/432 0.74 (0.55-0.98) 4 127/222 0.65 (0.46-0.93) Risk category MO int/high 342/855 0.75 (0.61-0.93) MO high 49/77 0.61 (0.35-1.08) M1 NED 37/57 0.48 (0.25-0.92) Sarcomatoid features Present 59/111 0.56 (0.33-0.96) Absent 339/829 0.75 (0.60-0.92) 0.1 0.5 1 1.5 "Assessed with PD-L1 IHC 22C3 pharmDx. PD-L1 combined positive score (CPS) is the # of PD-L1-staining Favors pembro Favors placebo cells (tumor cells, lymphocytes, and macrophages) divided by the total # of viable tumor cells, multiplied by 100. The 95% CI boundary for overall DFS is indicated by the shaded column. Median follow-up to data cutoff (Sept 25, 2024): 69.5 months (range, 60.2-86.9).

12 How to assess the risk of relapse? I FOX CHASE EMPLE HEALTH Prediction of Progression after Radical Nephrectomy Memorial Sloan Kettering for Patients with Clear Cell Renal Cell Carcinoma Assure RCC Prognostic Cancer Center A Stratification Tool for Prospective Clinical Trials Nomogram Risk of Recurrence Following Risk factor Posses PTIs 0 A post operative prediction model which provides comprehensive review of expected oncelogical outcomes in patients with renal cell carcinoma Surgery prib 2 pT2 3 (T)a/ble T4 4 0 RENAL CELL CARCINOMA pN1-2" 2 Disease Free Survival (DFS) Risk RECURRENCE-FREE PROBABILITY Turnor size to on 0 OFS intermed Pask Group Category Tumor size 10 on I S YEAR Fuluman grok 1-11 0 Furman grade III Furman gode N % Nacrods - 0 Disease Free Survival (DFS) Probability 3. 4. & 7. 1. 9. 10. 89 Necrods yes 2. 6. Leibevich Scores 5-year metastasis free survival 10. year metastails free service year year year year year year year year year year tip. Lew-risk 97.1% 92.5% 82.6% 69.5% 60.3% 53.7% 47.8% 43.3% 19.0% 56.5% 11.8% 31.4% 2-5 73.8% 64.9% tip High-risk 31.2% 23.6% 100 Adapted from Leibertch " al 2013. Leibersch points IN owned based as purhology variable an patients receive ** score depicied sogether with and 10 year metastasis free servival from the I many original study including 1671 patients. aRCC dear cell RCC. according to purhology report. to No refers to to incoment of viage. N-mage based in the 2002 ADCC TNM dissification 2 https://cancernomograms.com/nomograms/492 https://www.mskcc.org/nomograms/renal/post_op Leibovich et al. Cancer 2003 Correa et al. Eur Urol 2021 Kattan et al. J Urol 2001 Leibovich et al. Eur Urol 2018 ASCO Genitourinary #GU25 PRESENTED BY: Laurence ALBIGES, MD PhD ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY Cancers Symposium Presentation is property of the author and ASCO Permission required for reuse contact permissions@asco.org KNOWLEDGE CONQUERS CANCER --- 19 How to inform the patients? Recommendation Strength rating If adjuvant therapy is planned: Strong Discuss the contradictory results available from adjuvant ICI trials with the patient to facilitate shared decision- making Inform the patient about the potential risk of overtreat- ment and immune-related side effects if adjuvant therapy is considered Bedke J, et al. Updated European Association of Urology Guidelines on the Use of Adjuvant Immune Checkpoint Inhibitors and Subsequent Therapy for Renal Cell Carcinoma. Eur Urol. 2025 Feb 3:S0302-2838(25)00026-0. ASCO Genitourinary Cancers Symposium #GU25 PRESENTED BY: Laurence ALBIGES, MD PhD ASCO AMERICAN SOCIETY OF CUNICAL ONCOLOGY Presentation is property of the author and ASCO Permission required for reuse contact permissions@asco.org KNOWLEDGE CONQUERS CANCER --- 41 Can we use a biomarker to select for adjuvant? The predictive value approach KIM-1 is associated with DFS benefit of KIM-1 is associated with DFS benefit of Atezolizumab in IMMOTION 010 NIVO+IPI in CheckMate 914 DFS analyses in KIM-1, PD-L1 and T-effector1 gene Figure 4A. Association of KIM-1 levels with DFS N=584 subjects signature subgroups HR: Nivo+Ipi vs Placebo in CA209914 HR (95% CI) Baseline Atezolizumab Placebo Baseline subgroup n a HR (95% CI) KMI ist.quartle 1.37 (0.65-2.85) KIM-1-91 147 143 0.70 (0.50,0.97) KIM-1 219 1.13 (0.82. 1.54) KIMI 2nduartie 0.96 (0.51-1.82) 224 PD-L1 positive KMI 3rd.quartle 0.85 (0.45-1.62) 220 223 0.82 (0.61, 1.10) PD-L1 negative 151 139 1.04 (0.73, 1.48) KIMI 0.6 (0.34-1.04) T-effectormon 191 176 0.87 (0.63.1.21) T-effectoriow 180 186 0.97 (0.72. 1.33) HR 0.2 1.0 2 Improved Poorer DFSHR Survival Survival POLY Atezolizumab better Placebobetter - I Xu W. et al AACR 2024 Abstract 5151 2024 ASCO #ASCO24 - Lawrence MD, biomerker INCORD ASCO Cancer Res (2024) 84 (6_Supplement): 5151 ASCO Genitourinary #GU25 PRESENTED BY: Laurence ALBIGES, MD PhD ASCO AMERICAN SOCIETY OF CUNICAL ONCOLOGY Cancers Symposium Presentation is property of the author and ASCO Permission required for reuse contact permissions@asco.org KNOWLEDGE CONQUERS CANCER --- 42 Can we use a biomarker to select for adjuvant? The ctDNA approach: are we getting better in RCC? Patient 65 Large scale retrospective longitudinal monitoring in 1 ctDNA (MTM/mL) post operative setting is needed to further move to 0.1 prospective trial validation 0.01 ND 0-0-0-0 ctDNA 0 5 10 15 1.00 HR 1.31 1.00 (95% CI: 0.77-2.23) Time Since First ctDNA Time Point (months) ctDNA HR 1.14 (tDNA positive - 0.75 (95% Cl:0.81-1.62) | Procebility of survival e 0.75 tONA negative PD Axitinit/pembrolizumab 0.50 0.50 ctDNA*: HR 0.58 (95% CI: 0.43-0.79) Probability of overall survival Basu et al. JCO Precison Oncology 2024 0.25 0.25 ctDNA HR 0.59 (95% CI: 0.41-0.86) Real-world data 0 0 commercial ctDNA testing 0 10 20 30 40 50 0 10 20 30 40 50 No. risk Time (months) Time (months) (Signatera, Natera, Inc) Atezolizumab 184 144 85 44 5 0 184 174 129 57 10 0 ctDNA Observation 183 140 90 46 6 0 183 170 130 65 7 0 N= 92 (490 plasma samples) pts Atezolizumab 116 48 25 13 2 0 116 88 55 25 4 0 ctDNA* Observation 98 17 10 5 1 0 98 54 24 11 1 0 with metastatic RCC Powles et al. Nature 2021 ASCO Genitourinary #GU25 PRESENTED BY: Laurence ALBIGES, MD PhD ASCO AMERICAN SOCIETY OF CUNICAL ONCOLOGY Cancers Symposium Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER

Updated OS, ITT Population Pembro Placebo (N = 496) (N = 498) Events, n 68 99 Median, mo (95% CI) NR (NR-NR) NR (NR-NR) 100 96.3% 93.9% 91.2% Median follow-up was 69.5 months (range, 60.2-86.9) 93.9% 87.7% 90 86.1% 89.5% 80 86.0% 82.3% 79.4% 70 60 os, % 50 Pembrolizumab 40 Placebo 30 HR 0.66 (95% CI 0.48-0.90) 20 10 24 months 36 months 48 months 60 months 72 months 0 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 No. at Risk Months Key secondary OS endpoint was met at IA3 and Pembrolizumab 496 489 486 484 479 470 468 462 452 445 442 436 426 310 198 121 50 3 0 was not formally statistically tested thereafter. Placebo 498 494 487 483 476 463 455 441 433 423 419 413 400 284 177 111 46 4 0 Data cutoff date: September 25, 2024.

[Slide 1] Litespark-022: 28% risk reduction in recurrence Keynote-564: 37% risk reduction in recurrence Absolute Risk Reduction at 2 years of 7% Absolute Risk Reduction at 2 years of 11% 100 91.9% 28.3 mo Follow-up Updated Analysis: 30.1 mo Follow-Up 90 100 24-mo 80.7% rate 85.2% 80 75.8% 90 80 78.3% 70 73.7% 68.6% 70 60- 60 DFS,% * F % 67.3% 50 50 40 HR 0.72 (95% CI, 0.59-0.87) 40 HR 0.63 (95% CI 0.50-0.80) 30 P = 0.0003* 30 Nominal P < 0.0001 20 20 10- 12 months 24 months % submits Pembro 10 Placebo 0 0 0 6 12 18 24 30 36 42 0 5 10 15 20 25 30 35 40 45 50 No. Risk Months Months Pembrolizumab 921 850 805 669 451 153 35 0 No. risk belzutifan Pembro 496 458 416 389 361 255 135 77 37 0 0 Pembrolizumab 920 823 759 619 417 140 38 0 Placebo 498 437 389 placebo 356 325 230 125 74 33 1 0 Early and stable separation of the curves that persists after completion of 12 months of belzutifan Will there be a tail of the curve materialize in LS-022? Did differences in eligibility (M1 NED fraction, risk strata) result in different performance of pembrolizumab? ASCO Genitourinary #GU26 PRESENTED BY: Dr. Katy Beckermann, MD, PhD. @katy_ beckermann ASCO AMERIC SOCIETY OF Cancers Symposium CUNICAL ONCOLOGY Presentation is property of the author and ASCO Permission required or revie, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER --- [Slide 2] Litespark-022: 28% risk reduction in recurrence Keynote-564: 37% risk reduction in recurrence Absolute Risk Reduction at 2 years of 7% Absolute Risk Reduction at 2 years of 11% 100 91.9% 28.3 mo Follow-up Updated Analysis: 30.1 mo Follow-Up 90 100 24-mo 80.7% rate 85.2% 80 75.8% 90 80 78.3% 70 73.7% 68.6% 70 60- 60 DFS,% * F % 67.3% 50 50 40 HR 0.72 (95% CI, 0.59-0.87) 40 HR 0.63 (95% CI 0.50-0.80) 30 P = 0.0003* 30 Nominal P < 0.0001 20 20 10- 12 months 24 months % submits Pembro 10 Placebo 0 0 0 6 12 18 24 30 36 42 0 5 10 15 20 25 30 35 40 45 50 No. Risk Months Months Pembrolizumab 921 850 805 669 451 153 35 0 No. risk belzutifan Pembro 496 458 416 389 361 255 135 77 37 0 0 Pembrolizumab 920 823 759 619 417 140 38 0 Placebo 498 437 389 placebo 356 325 230 125 74 33 1 0 Early and stable separation of the curves that persists after completion of 12 months of belzutifan Will there be a tail of the curve materialize in LS-022? Did differences in eligibility (M1 NED fraction, risk strata) result in different performance of pembrolizumab? ASCO Genitourinary #GU26 PRESENTED BY: Dr. Katy Beckermann, MD, PhD. @katy_ beckermann ASCO AMERIC SOCIETY OF Cancers Symposium CUNICAL ONCOLOGY Presentation is property of the author and ASCO Permission required or revie, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER

Multiple risk calculators exist UISS (Zisman et al 2002) — DFS of 80.4% at 5 years SSIGN (Frank et al 2002) - DFS of 89.8% at 5 years MSKCC (Kattan et al 2001) - DFS of 90% at 5 years 2018 Leibovich (Leibovich et al 2018) - PFS of 75% at 5 years ASSURE (Andres et al 2021) - DFS of 78.5% at 5 years 2025 ASCO #ASCO25 PRESENTED BY: ASCO AMERICAN SOCIETY or CUNICAL ONCOLOGY ANNUAL MEETING Presentation - property of the who and ASCO Permission required lo - sentact perrissons@asco.org KNOWLEDGE CONQUERS CANCER --- 17 Cytoreductive nephrectomy (CN) SURTIME and CARMENA showed worse outcomes with immediate CN1-2 Post-hoc analysis suggest better outcomes with CN in the IO era³⁻⁴ Current SOC is to consider CN only if symptomatic or in selected cases Delayed CN is recommended over immediate/upfront CN in these selected cases Ongoing Phase 3 trials may clarify this issue (NORDIC-SUN-Trial, PROBE and others) ex A, et al. JAMA Oncol. 2019 PMID 30543350 3. Shen X-P, et al. Eur Rev Med Pharmacol Sci. 2023 PMID 37401306 lejean A, et al. NEJM 2018. PMID 29860937 4. Grim M-O, et al. Eur Urol. 2024. PMID 37852850 ASCO #ASCO25 PRESENTED BY: ASCO AMERICAN SOCIETY O CUNICAL ONCOLOGY INUAL MEETING Presentation . property of the author and ABCO Permission required for - contact perrissions@asco.org KNOWLEDGE CONQUERS CANCER --- Immune related adverse events 35 35 30 R Incidence of prednisone use Propertion patients (%) 25 20 15 Propertion of patients (%) 25 R 15 10 10 5 5 0 0 IO/TKI ~11-27%1-2 0 1 10152025 303540465055606570 0 5 1015202530 3540 4550 5560 65 70 Time (svk) Time (wk) 10/10 ~35%³ 40 Proportion of patients 35 + 30- All categories 25-4 20 - Skin 15- 10- Gastrointestinal 0 5 10 15 20 25 30 R 40 Hepatic Time (svk) Endocrine Pulmonary Renal 1. Powles T, et al. ESMO Open. 2024. PMID 38642472 Hypersensitivity/ 2. Rini BI, et al. NEJM 2019. PMID 30779529 infusion reaction 3. Choueiri TK, et al. NEJM 2023. PMID 37163623 Neurologic 4. Tang S-Q, et al. Cancer Res Treat. 2020. PMID 33171025 2025 ASCO #ASCO25 ASCO AMERICAN SOCIETY or PRESENTED BY: CUNICAL ONCOLOGY ANNUAL MEETING Presentation property of the who and ASCO Permission required for rease, contact petrinsions@asco.org KNOWLEDGE CONQUERS CANCER --- Key Takeaways Recommendation for adjuvant pembrolizumab should be based on patient's risk level and informed decision making GrO Cytoreductive nephrectomy can be considered in select patients Management of irAE can be a multidisciplinary effort 025 ASCO PRESENTED BY: #ASCO25 ASCO AMERICA CLINICAL NNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse; contact permissions@asco.org KNOWLEDGE CONQUER