What Community Oncologists Should Watch for at ASCO GU 2025

3D render of genitourinary system: © Leo Viktorov - stock.adobe.com

As the 2025 ASCO Genitourinary Cancers Symposium (ASCO GU) approaches, several highly anticipated studies are set to shape the future of treatment for prostate, kidney, bladder, and other genitourinary cancers. Here’s a roundup of the key trials to watch out for at the meeting:

Prostate Cancer:

LBA18: TALAPRO-2 Study

The phase 3 TALAPRO-2 trial (NCT03395197) is evaluating the combination of talazoparib (Talzenna), a PARP inhibitor, and enzalutamide (Xtandi), an androgen receptor inhibitor, as a first-line treatment in metastatic castration-resistant prostate cancer (mCRPC).¹

It was previously reported that this combination led to statistically significant and meaningful improvements in overall survival (OS) in all-comers as well as patients with homologous recombination repair gene–mutated mCRPC.

The final OS data will provide valuable insights.

LBA138: Mevrometostat + Enzalutamide in mCRPC

This randomized study is looking at the combination of mevrometostat, an EZH2 inhibitor, with enzalutamide in patients with mCRPC. As an enhancer of the EZH2 gene, mevrometostat could improve outcomes for patients with castration-resistant disease, and the study’s results may expand therapeutic options in this setting.

Abstract 17: ENZA-p Study

In the ENZA-p trial (NCT04419402), investigators are assessing the combination of ¹⁷⁷lutetium–prostate-specific membrane antigen-617 (¹⁷⁷Lu-PSMA-617; Pluvicto), a radiolabeled PSMA-targeting therapy, and enzalutamide vs enzalutamide monotherapy in patients with poor-risk, mCRPC.² With promising early data, the final survival and quality-of-life outcomes will offer critical insights for treatment decisions.

“This is the first randomized trial combining an androgen receptor signaling inhibitor, enzalutamide, with ¹⁷⁷Lu-PSMA-617. It provides strong evidence for an enhanced anti-cancer effect with the combination of enzalutamide and ¹⁷⁷Lu-PSMA-617 based on the primary end point, PSA-progression-free survival [PFS],” said Louise Emmett, MD, FRACP, during an oral presentation of the findings at the ESMO meeting. Emmett is the director of theranostics and nuclear medicine at St. Vincent’s Hospital in Sydney, Australia.

Abstract 20: STOPCAP Meta-analysis

The STOPCAP meta-analysis is pooling data from individual participant studies to determine which patients with metastatic hormone-sensitive prostate cancer (mHSPC) benefit most from androgen receptor pathway inhibitors (ARPIs). As the first-line standard of care in mHSPC evolves, this analysis could help identify biomarkers for patient selection.

Kidney Cancer:

Abstract 438: COSMIC-313

The COSMIC-313 trial (NCT03937219) is examining the combination of cabozantinib (Cabometyx), nivolumab (Opdivo), and ipilimumab (Yervoy) in untreated advanced renal cell carcinoma (aRCC).³

“The COSMIC-313 certainly was a positive study on a first interim analysis, if you will. This was comparing the triplet of nivolumab plus ipilimumab and cabozantinib vs ipi/nivo with a primary end point of PFS. The triplet indeed did improve PFS in the intention-to-treat population [and] more so was in the intermediate-risk patient population per the IMDC risk stratification,” Yousef Zakharia, MD, a medical oncologist and clinical associate professor of internal medicine-hematology, oncology, and blood and marrow transplantation in the Department of Internal Medicine at University of Iowa Hospitals & Clinics, previously told Targeted Oncology^TM, in an interview.

Experts hope that the final results from the trial will shed light on the effectiveness of triple therapy in improving patient outcomes compared with conventional approaches.

Abstract 439: CheckMate 9ER Trial

At the ASCO GU meeting, final follow-up results from CheckMate 9ER, comparing the combination of nivolumab and cabozantinib to sunitinib (Sutent)in untreated aRCC, will be presented.⁴

In January 2021, the FDA approved nivolumab plus cabozantinib for the first-line treatment of patients with advanced RCC based on earlier data from CheckMate-9ER. Data from the 55-month follow-up of the study shared during the 2024 Genitourinary Cancers Symposium showed that nivolumab plus cabozantinib continues to provide a meaningful improvement over sunitinib in PFS, OS, and overall response rate (ORR). In the intention-to-treat population, the PFS by BICR was 16.4 months (95% CI, 12.5-19.3) with the doublet vs 8.4 months (95% CI, 7.0-9.7) with sunitinib (HR, 0.58; 95% CI, 0.49-0.70). The median OS with nivolumab plus cabozantinib was 46.5 months (95% CI, 40.6-53.4) vs 36.0 months (95% CI, 29.2-42.8) with sunitinib (HR, 0.77; 95% CI, 0.63-0.95). The ORR by BICR was 55.7% with the doublet vs 27.7% with sunitinib.

The trial has already shown promising survival benefits, and this update will offer a deeper look at long-term efficacy and safety.

Abstract 440: KEYMAKER-U03 Substudy 03B

The overall KEYMAKER-U03 trial is evaluating combinations of immunotherapy and targeted therapies for the treatment of patients with clear cell renal cell carcinoma (ccRCC). Results from arm B5 of the phase 1/2 KEYMAKER-U03B substudy (NCT04626518) of KEYMAKER-U03, which were presented at the 2023 ASCO Annual Meeting, showed that at a median follow-up of 6.9 months, a regimen combining the HIF-2α inhibitor belzutifan and the VEGF-TKI lenvatinib (Lenvima) elicited an ORR of 50% (95% CI, 29-71) among 24 patients who had received at least 2 postbaseline scans. All of the responses were partial responses.⁵

This updated analysis could provide new insights into how immune checkpoint inhibitors can be integrated with targeted treatments in this aggressive form of kidney cancer.

Abstract 441: Casdatifan in the ARC-20 Study

Casdatifan is a novel aHIF-2α inhibitor being assessed as a monotherapy for the treatment of patients with previously treated ccRCC. The ARC-20 study’s findings will be pivotal in understanding its potential to address unmet needs in metastatic disease.

Prior results from the dose-escalation portion of the study were presented at the 2024 EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics and showed that in the 100-mg daily dose expansion cohort of ARC-20 (n = 32), casdatifan achieved an objective response rate (ORR) of 34%. The confirmed ORR was 25% among evaluable patients, with 2 additional responses pending confirmation at a median follow-up of 11 months (range, 3-15+).⁶

Patients responded to casdatifan in a median time of 2.8 months (range, 1.2-5.5), and the disease control rate was 81.3% (90% CI, 63.6%-92.8%). The median PFS has not been reached yet, with 18.8% of patients experiencing disease progression. Patients in this cohort were heavily pretreated, with all having progressed on at least 2 prior therapies, including anti–PD-1 agents and tyrosine kinase inhibitors.

Abstract 444: CALYPSO Trial

The CALYPSO study (NCT02819596) is focusing on MET-driven advanced papillary renal cancer and investigators will present final OS data at this meeting. The addition of circulating tumor DNA analysis may provide a more comprehensive understanding of how this subset of RCC responds to treatment.

Bladder:

Abstract 658: CheckMate 274

This study (NCT02632409) is investigating the use of nivolumab in high-risk muscle-invasive urothelial carcinoma as adjuvant therapy. Additional efficacy outcomes, including OS, aim to give more clarity on nivolumab's role in post-surgery treatment.⁷

“We've seen OS data that certainly appear to be suggesting that patients may derive an OS benefit with this regimen, particularly those individuals [who] are PD-L1 positive,” Rana R. McKay, MD, professor of medicine and urology at UC San Diego School of Medicine, previously told Targeted Oncology^TM, during a Case-Based Roundtable event.

Abstract 659: NIAGARA Study
This analysis is looking at additional efficacy and safety outcomes in muscle-invasive bladder cancer patients from the NIAGARA study (NCT03732677), focusing on pathological complete response (pCR) as a predictor of long-term survival.⁸

McKay previously discussed this trial of durvalumab (Imfinzi) plus neoadjuvant chemotherapy compared with neoadjuvant chemotherapy alone, sharing that those in the durvalumab arm had superior event-free survival.

“The uniqueness of this study was it actually allowed enrollment of patients with a GFR [glomerular filtration rate] of greater than 40 [mL/min per 1.73 m²] so it had a slightly lower GFR threshold than historically utilized, and patients received cisplatin, gemcitabine, durvalumab, pre- and post- surgery and the post-surgery treatment was not dependent on pathologic responses at the time of surgery, and the control arm patients did not receive adjuvant immunotherapy,” McKay added. “So there are some questions that are left unanswered with the NIAGARA study, particularly around [whether] patients with a pCR need outback treatment, and then what's the performance of the control arm in the context of adjuvant immunotherapies now demonstrating improvements in outcomes?”

Abstract 662: FORAGER-1 Study
LY3866288 (LOXO-435), a FGFR3 inhibitor, is being tested in a first-in-human phase 1 trial. This targeted therapy could significantly impact the treatment of bladder cancers with FGFR3 alterations, and its initial results may offer new hope for this subgroup.

Abstract 663: TROPION-PanTumor01
This updated analysis from the TROPION-PanTumor01 study (NCT03401385) willpresent data on datopotamab deruxtecan (Dato-DXd), a novel antibody-drug conjugate, in patients with locally advanced or metastatic urothelial cancer. The results could redefine the standard of care in this difficult-to-treat population.

Abstract 664: EV-302
This phase 3 global study (NCT04223856) will show the updated analysis of enfortumab vedotin-ejfv (Padcev) combined with pembrolizumab vs chemotherapy in previously untreated locally advanced or metastatic urothelial carcinoma.

The past year has seen the FDA approvals of enfortumab vedotin in combination with pembrolizumab for patients with locally advanced or metastatic urothelial cancer in December 2023, and nivolumab plus cisplatin and gemcitabine for patients with unresectable or metastatic urothelial carcinoma in March 2024.

The results may shift treatment strategies in this challenging cancer type.

Other Notable Studies:

Abstract 618: COTRIMS Trial
The COTRIMS trial’s final results will provide crucial insights into the role of retroperitoneal lymphadectomy in metastatic seminoma, potentially influencing treatment strategies for this rare testicular cancer.

Abstract 1: EPIC-A Trial
This phase 2 trial evaluates cemiplimab, an immune checkpoint inhibitor, in combination with standard chemotherapy followed by maintenance treatment in locally advanced or metastatic penile carcinoma. The findings will highlight novel therapeutic approaches for this rare and often under-treated cancer.

REFERENCES:

1. Pfizer’s TALZENNA® in combination with XTANDI® prolongs overall survival in phase 3 TALAPRO-2 trial. News release. Pfizer. October 10, 2024. Accessed February 11, 2025. https://tinyurl.com/yc2kypjp

2. Enzalutamide and 177Lu-PSMA-617 in poor-risk, metastatic, castration-resistant prostate cancer (mCRPC): A randomised, phase II trial: ENZA-p (ANZUP 1901). Presented at the European Society of Medical Oncology (ESMO) Congress. October 20-24, 2023. Madrid, Spain. Abstract LBA84

3. Choueiri TK, Powles T, Albiges L, et al; COSMIC-313 Investigators. Cabozantinib plus nivolumab and ipilimumab in renal-cell carcinoma. N Engl J Med. 2023;388(19):1767-1778. doi:10.1056/nejmoa2212851

4. Bourlon MT, Escudier B, Burotto M, et al. Nivolumab plus cabozantinib versus sunitinib for previously untreated advanced renal cell carcinoma: results from 55-month follow-up of the CheckMate 9ER trial. J Clin Oncol. 2024;42 (suppl 4):362. doi:10.1200/JCO.2024.42.4_suppl.362

5. Albiges L, Beckermann K, Miller WH, et al. Belzutifan plus lenvatinib for patients (pts) with advanced clear cell renal cell carcinoma (ccRCC) after progression on a PD-1/L1 and VEGF inhibitor: Preliminary results of arm B5 of the phase 1/2 KEYMAKER-U03B study. J Clin Oncol. 41, 2023 (suppl 16; abstr 4553) doi: 10.1200/JCO.2023.41.16_suppl.4553

6. Choueiri TK, Garmezy B, Park SH, et al. Casdatifan in patients with previously treated clear cell renal cell carcinoma and other solid tumors: preliminary results from ARC-20, a phase 1, open-label, dose-escalation and expansion study. Presented at: 2024 EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics; October 23-25, 2024; Barcelona, Spain.

7. Chehrazi-Raffle A, Feinberg B, John W, et al. Characteristics of patients (pts) with muscle-invasive urothelial carcinoma (MIUC) who received adjuvant nivolumab (NIVO) or adjuvant platinum-based chemotherapy (CHEMO) in the real-world (RW) setting. J Clin Oncol. 2024;42(suppl 4): Abstract 565. doi:10.1200/JCO.2024.42.4_suppl.56

8. Powles T, Van der Heijden MS, Galsky M, et al. A randomized phase III trial of neoadjuvant durvalumab plus chemotherapy followed by radical cystectomy and adjuvant durvalumab in muscle-invasive bladder cancer (NIAGARA). Presented at: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain. Abstract LBA5.