Inside the Most Anticipated Genitourinary Cancer Abstracts: What to Watch at ESMO 2025

The 2025 ESMO Congress is fast approaching, and OncLive® spoke with leading experts in the genitourinary (GU) oncology field to gather their perspectives on the abstracts and data they are most anticipating from this year’s meeting.

“[At the 2025 ESMO Congress] there will be many exciting abstracts in [GU oncology], so it is difficult to pick just a handful. In the frontline settings, we are in need of novel agents to improve the rate of durable responses. Kidney cancer is still in need of predictive and prognostic biomarkers, and there is much interesting work being done in this space,” David A. Braun, MD, PhD, explained.

To gain insights on the most anticipated GU oncology presentations at the upcoming congress, we spoke with:

• David A. Braun, MD, PhD - assistant professor of medicine (medical oncology), and Louis Goodman and Alfred Gilman Yale Scholar at Yale Medical School in New Haven, Connecticut.
• Alan Tan, MD - associate professor of medicine, Division of Hematology Oncology at Vanderbilt University Medical Center in Nashville, Tennessee.
• Axel Merseburger, MD, PhD - professor and chair of the Department of Urology at University Hospital Schleswig-Holstein in Lübeck, Germany.

What Updates Can We Expect in Renal Cell Carcinoma (RCC) at ESMO 2025?

LBA96: First-line pembrolizumab-based regimens for advanced clear cell renal cell carcinoma: KEYMAKER-U03 substudy 03A

Session information: 8:30 am CEST, Saturday, October 18

2596MO: Phase Ib/II trial of ipilimumab, nivolumab, and ciforadenant (adenosine A2a receptor antagonist) in first-line advanced renal cell carcinoma (RCC), a kidney cancer research consortium study

Session information: 4:00 pm CEST, Friday, October 17

Braun: I am excited to see novel mechanisms of actions, such as adenosine receptor blockade [such as ciforadenant (CPI-444) combined with ipilimumab (Yervoy) and nivolumab (Opdivo)], and the frontline pembrolizumab [Keytruda]-based regimens investigated in the [phase 3] KEYMAKER-U03A [NCT04637594] study.¹

2594MO: Association of circulating kidney injury molecule-1 (KIM-1) levels with clinical outcomes in advanced renal cell carcinoma (aRCC): Retrospective analysis of COSMIC-313

Session information: 8:30 am CEST, Sunday, October 19

2599MO: Soluble MAdCAM-1 predicts outcomes in patients with metastatic renal cell carcinoma: Results from three independent clinical trials

Session information: 8:30 am CEST, Sunday, October 19

2591O: Efficacy of cabozantinib and nivolumab in cluster 1/2 metastatic clear cell renal cell carcinoma: Results from OPTIC RCC, a phase II trial of a novel RNAseq-based biomarker

Session information: 8:30 am CEST, Saturday, October 18

Braun: KIM-1 is rapidly emerging as a leading biomarker candidate [in RCC], and it will be exciting to see how it performs again in a modern metastatic setting [in] COSMIC-313. We saw the circulating biomarker MAdCAM-1 first presented at ASCO 2025, so it will be interesting to see how it performs in additional clinical studies. Finally, we are starting to see the first prospective biomarker studies in RCC. The phase 2 OPTIC RCC trial [NCT05358958] classified ccRCC into molecular subtypes based on RNA-sequencing, [and investigators] will present initial results on outcomes for patients with angiogenic subtypes treated with nivolumab plus cabozantinib [Cabometyx].

LBA93: First results from RAMPART: An international phase 3 randomised-controlled trial of adjuvant durvalumab monotherapy or combined with tremelimumab for resected primary renal cell carcinoma (RCC) led by MRC CTU at UCL

Session information: 8:30 am CEST, Saturday, October 18

Braun: In the adjuvant space, we have seen one positive immune checkpoint inhibitor trial [the phase 3] KEYNOTE-564 trial (NCT03142334)], but also a series of negative trials [including the phase 3 CheckMate-914 (NCT03138512), IMmotion-010 (NCT03024996), and PROSPER (NCT03055013) trials]. It will be important to see the final results of the phase 3 RAMPART trial [NCT03288532] at ESMO, a randomized trial of durvalumab [Imfinzi] vs durvalumab plus tremelimumab vs placebo. Ultimately, it will be important to see if this further supports the development of immune checkpoint inhibitor therapy in the adjuvant setting.

LBA94: LenCabo: A randomized phase II multicenter trial of lenvatinib plus everolimus (len/eve) versus (vs) cabozantinib (cabo) in patients (pts) with metastatic clear cell RCC (ccRCC) that progressed on PD-1 immune checkpoint inhibition (ICI)

Session information: 8:30 am CEST, Saturday, October 18

Braun: In the treatment refractory setting, we rarely see TKI regimens compared to one another – this is a practical but important question. We will see the results of the phase 2 LenCabo trial [NCT05179662] from MD Anderson [Cancer Center], comparing cabozantinib with lenvatinib [Lenvima] plus everolimus after immune checkpoint inhibitor therapy.

2595MO: Exploratory analysis of chromophobe renal cell carcinoma in the SUNNIFORECAST trial comparing ipilimumab plus nivolumab vs standard of care as first-line treatment

Session information: 8:30 am CEST, Saturday, October 18

Braun: In the non–clear cell setting, metastatic chromophobe renal cell carcinoma represents a particular challenge, with few dedicated studies. The phase 2 SUNNIFORECAST study [NCT05239728] of ipilimumab plus nivolumab vs sunitinib [Sutent] in non–clear cell RCC showed some initial promising response rates for immune checkpoint inhibitor therapy for chromophobe RCC, which study somewhat in contrast to prior studies. It will therefore be excited to see the dedicated exploratory analysis of chromophobe RCC in SUNNIFORECAST.

What Updates Can We Expect in Bladder Cancer at ESMO 2025?

LBA107: ALBAN: A phase 3, randomized, open-label, international study of intravenous (iv) atezolizumab and intravesical Bacillus Calmette-Guérin (BCG) vs BCG alone in BCG-naïve high-risk, non-muscle-invasive bladder cancer (NMIBC)

Session information: 2 pm CEST, Friday, October 17

Merseburger: The phase 3 ALBAN study [NCT03799835] could be a game-changer for patients with BCG-unresponsive high-risk non–muscle-invasive bladder cancer [NMIBC], a population with limited bladder-preserving options. By combining atezolizumab [Tecentriq] with intravesical BCG, this trial explores whether systemic checkpoint inhibition can enhance local immune responses. If positive, the results could establish a new standard of care and reduce the need for early cystectomy in this challenging setting.

LBA2: Perioperative (periop) enfortumab vedotin (EV) plus pembrolizumab (pembro) in participants (pts) with muscle-invasive bladder cancer (MIBC) who are cisplatin-ineligible: The phase 3 KEYNOTE-905 study

Session information: 4:30 pm CEST, Saturday, October 18

Tan: Two years ago at ESMO 2023, enfortumab vedotin-ejfv [Padcev] plus pembrolizumab doubled progression-free survival and overall survival (OS), establishing a new standard of care in metastatic urothelial cancer.¹ This combination is poised to become a new standard of care as perioperative treatment in cisplatin-ineligible patients with MIBC. The current perioperative treatment for cisplatin-eligible patients is gemcitabine, cisplatin, and durvalumab, which showed pathologic complete response [pCR] rate of 37% and superior OS over gemcitabine and cisplatin. The results of this [KEYNOTE-905] are highly anticipated. Enfortumab vedotin plus pembrolizumab is associated with 68% ORR in the metastatic setting, and it is anticipated that pCR [rate] will be significantly higher than previous platinum-based chemotherapy benchmarks. There will likely continue to be unanswered questions associated with this regimen, even if the results are highly positive, as the regimen also includes 6 cycles of post-operative enfortumab vedotin and 14 cycles of post-operative pembrolizumab.Is post-operative treatment necessary if patients achieved pCR?Does circulating tumor DNA [ctDNA] status play a role in this decision?

3068O: Adjuvant nivolumab vs placebo for high-risk muscle-invasive urothelial carcinoma: 5-year efficacy and ctDNA results from CheckMate 274

Session information: 2 pm CEST, Friday, October 17

Merseburger: Updated OS results from the phase 3 CheckMate 274 [NCT02632409] are highly anticipated, as they could consolidate adjuvant nivolumab as the standard of care after radical surgery in high-risk MIBC. Earlier data demonstrated a significant disease-free survival [DFS] benefit,² and mature OS data will be critical for global practice patterns and regulatory decisions.

LBA8: IMvigor011: a Phase 3 trial of circulating tumour (ct)DNA-guided adjuvant atezolizumab vs placebo in muscle-invasive bladder cancer

Session information: 4:30 pm CEST, Monday, October 20

Tan: Topline results [from the phase 3 IMvigor011 trial (NCT04660344)] demonstrated significant improvement in DFS and OS in ctDNA-positive patients.³ ctDNA has been a very promising biomarker in urothelial cancer ever since imVIGOR-010, a study that was negative for its primary endpoint of DFS, did demonstrate important prognostic and predictive potential in selected patients who were ctDNA positive receiving adjuvant atezolizumab in high-risk urothelial carcinoma. The use of ctDNA has picked up commercially in recent years, although guidance for how providers should use ctDNA in patients was lacking, due to the lack of prospective evidence. This trial will help close this gap and inform clinical utility of ctDNA in MIBC for the first time. Future questions will remain. For instance, will ctDNA selection only be applicable to the use of atezolizumab, or would it be appropriate to utilize this methodology with nivolumab and pembrolizumab?

References

1. Powles TB, Perez Valderrama B, Gupta S, et al. EV-302/KEYNOTE-A39: Open-label, randomized phase III study of enfortumab vedotin in combination with pembrolizumab (EV+P) vs chemotherapy (Chemo) in previously untreated locally advanced metastatic urothelial carcinoma (la/mUC). Presented at: ESMO Congress 2023; October 20-24, 2023; Madrid, Spain. Abstract LBA6.
2. Milowsky MI, Galsky MD, Witjes JA, et al. Adjuvant nivolumab vs placebo for high-risk muscle-invasive urothelial carcinoma: additional efficacy outcomes including overall survival in patients with muscle-invasive bladder cancer from CheckMate-274. J Clin Oncol. 2025;43(suppl 5):658. doi:10/1200/JCO.2025.43.5_suppl.658
3. IMvigor011 bladder cancer trial achieves positive results, with Signatera strongly predicting adjuvant immunotherapy benefit. News release. Natera. August 18, 2025. Accessed October 7, 2025. https://www.natera.com/company/news/imvigor011-bladder-cancer-trial-achieves-positive-results-with-signatera-strongly-predicting-adjuvant-immunotherapy-benefit/