ASCO GU 2026 Preview: Highlights of Key Trials in Bladder, Kidney, Prostate, and Rare Cancers

In a preview of the upcoming 2026 ASCO Genitourinary Cancers Symposium, Rahul Parikh, MD, PhD, professor of medicine, University of Kansas and KU Medical Center shared his perspective on several presentations he is anticipating across the major disease settings.

Bladder Cancer

Parikh expressed significant interest in a late breaking abstract to be presented by Matthew Galsky, MD, professor of medicine, deputy director of the Mt Sinai Tisch Cancer Center, codirector, Center of Excellence for Bladder Cancer, in New York, New York, concerning the phase 3 KEYNOTE-B15 trial (NCT04700124).¹ This trial is evaluating the role of perioperative enfortumab vedotin (Padcev), an antibody-drug conjugate, in combination with pembrolizumab (Keytruda). Patients with muscle-invasive bladder cancer who were eligible for cisplatin-based neoadjuvant chemotherapy were evaluated. The comparator arm in this trial is the standard regimen of cisplatin with gemcitabine.

Parikh contextualized this trial by referencing the earlier KEYNOTE-905 trial (NCT03924895),² also known as EV-303, which investigated the same combination in the perioperative space for patients who are cisplatin ineligible. In that earlier study, which had no standard neoadjuvant treatment to compare against, patients received 3 cycles of enfortumab vedotin with pembrolizumab before surgery, followed by 6 additional cycles after the procedure. The results showed a significant reduction in events, with the median event-free survival not reached in the treatment arm compared with 15.7 months for radical cystectomy with lymph node dissection alone, yielding an HR of approximately 0.4 (95% CI, 0.28–0.57; P<.001). Based on those findings, the combination is now FDA-approved for cisplatin ineligible patients.³

“With that, I think the combination currently has been FDA approved for patients who are [cisplatin] ineligible, and this is the next step for that, is to see how this compares to the existing standard of care using cisplatin [and] gemcitabine,” Parikh said. He noted that KEYNOTE-B15 represents that logical next step. “I think it's going to be a very interesting presentation, and it will be good to see what [are] the response rates, particularly, the complete response rates.”

Kidney Cancer

In the kidney cancer arena, Parikh is looking forward to LBA417, to be presented by Robert J. Motzer, MD, the Jack and Dorothy Byrne Chair in Clinical Oncology, and section head, kidney cancer, Memorial Sloan Kettering Cancer Center in New York, New York.

This presentation will detail the phase 3 LITESPARK-011 trial (NCT04586231),⁴ which is investigating second-line treatments for metastatic renal cell carcinoma. The standard frontline treatment typically involves a combination of a VEGF tyrosine kinase inhibitor (TKI) with immunotherapy or an immunotherapy/immunotherapy combination.

Parikh explained the background for this trial by referencing the prior CONTACT-03 study (NCT043338269),⁵ which examined whether rechallenging patients with an immunotherapy agent in combination with a VEGF TKI was superior to using a VEGF TKI alone. In that trial, the combination of atezolizumab (Tecentriq) with cabozantinib (Cabometyx) was compared with cabozantinib monotherapy. The results showed similar median progression-free survival between the 2 arms, at about 10.6 months for the combination and 10.8 months for cabozantinib alone, with an HR for death or disease progression of 1.03 and similar median overall survival. This established cabozantinib monotherapy as a frequently used second-line agent.

The LITESPARK-011 trial builds on this by comparing a different combination, belzutifan (Welireg), an HIF2α inhibitor, with the VEGF TKI lenvatinib (Lenvima), against cabozantinib monotherapy. Parikh noted that time to progression and overall survival are the primary end points. He also highlighted the importance of comparing the safety profile of the 2-agent combination against the single-agent arm, as this trial has the potential to shift the treatment paradigm in the second-line setting.

Prostate Cancer

For prostate cancer, Parikh highlighted a presentation⁶ by Fred Saad, CQ, MD, FRCS, FCAHS, professor, Department of Surgery, University of Montreal, and director, Prostate Cancer Research, Montreal Cancer Institute, Canada, regarding early data on actinium radioligand therapy. This represents the first-in-human assessment of actinium-225 PSMA, with dose escalation cohort results being presented.

Parikh explained that while the field of theranostics has expanded significantly with the approval oflutetium Lu 177 vipivotide tetraxetan (Pluvicto), actinium offers a different mechanism as an alpha emitter. The presentation will provide insight into the efficacy and safety profile of this novel agent, which he finds encouraging for the continued evolution of treatments for metastatic castration-resistant prostate cancer.

“Another prostate cancer study of interest is being presented by Neeraj Agarwal, MD, and focuses on a drug called mevrometostat,” Parikh said.⁷ Agarwal is professor of medicine and a Presidential Endowed Chair of Cancer Research at the Huntsman Cancer Institute, University of Utah, Salt Lake City.

This is a small molecule inhibitor of an enzyme known as EZH2, which functions as a histone methyltransferase and is frequently overexpressed in prostate cancer. The phase 3 trial combines this EZH2 blocker with enzalutamide (Xtandi) and compares it with enzalutamide with placebo. “It’s exploring a novel pathway, and I think it would be very interesting to see what results we find here,” Parikh said.

Other Rare Malignancies

Parikh also highlighted 2 abstracts concerning rarer malignancies. The first is the CLIMATE study (ACTRN12622000247774)⁸ in testicular cancer, a prospective investigation into the use of microRNA 371a-3p as a marker for minimal residual disease in patients with stage I testicular cancer. Currently, active surveillance for these patients relies on physical exams, imaging, and traditional tumor markers. MicroRNAs have shown high sensitivity and specificity for detecting and monitoring testicular cancer. This prospective data may help determine if this biomarker can be used to better stratify patients and identify who may need intervention sooner, moving beyond traditional risk factors like lymphovascular invasion or tumor size.

The second rare cancer abstract involves a drug called obrixtamig (BI 764532), which is being evaluated in the DAREON-5 study (NCT05882058), a large open-label trial that is evaluating patients with neuroendocrine malignancies.⁹ This drug is a bispecific antibody directed against the delta-like ligand 3 receptor, which is overexpressed in neuroendocrine and small cell lung cancer. Earlier studies in genitourinary cohorts demonstrated a high response rate of about 60%. He noted that Aman Chauhan, MD, of Sylvester Comprehensive Cancer Center, Miami, Florida, will present further data on the dose expansion phase, detailing the responses and adverse events seen in this challenging-to-treat patient population.

REFERENCES

1. Galsky MD, Balderrama BP, Maruzzo M et al. Neoadjuvant and adjuvant enfortumab vedotin (EV) plus pembrolizumab (pembro) for participants with muscl-invasive bladder cancer (MIBC) who are eligible for cisplatin: Randomize, open-label, phase 3 KEYNOTE-B15 study. Presented at: 2026 ASCO Genitourinary Cancers Symposium; February 26-28, 2026; San Francisco, CA. Abstract LBA630.

2. Vulsteke C, Adra N, Danchaivijitr P, et al. Perioperative Enfortumab Vedotin and Pembrolizumab in Bladder Cancer. N Engl J Med. Published online February 18, 2026. doi:10.1056/NEJMoa2511674

3. FDA approves pembrolizumab with enfortumab vedotin-ejfv for muscle invasive bladder cancer. FDA release. November 21, 2025. Accessed February 23, 2026. https://tinyurl.com/bcy3j4ey

4. Motzer RJ, Park SH, McDermott RS, et al. Belzutifan (bel) plus lenvatinib (lenva) versus cabozantinib (cabo) for advanced renal cell carcinoma (RCC) after anti–PD-(L)1 therapy: Open label phase 3 LITESPARK-011 study. Presented at: 2026 ASCO Genitourinary Cancers Symposium; February 26-28, 2026; San Francisco, CA. Abstract LBA417.

5. Pal SK, Albiges L, Tomczak P, et al. Atezolizumab plus cabozantinib versus cabozantinib monotherapy for patients with renal cell carcinoma after progression with previous immune checkpoint inhibitor treatment (CONTACT-03): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2023;402(10397):185-195. doi:10.1016/S0140-6736(23)00922-4

6. Saad F, Hotte SJ, Jayaram A, et al. First-in-human assessment of actinium-225-prostate-specific membrane antigen (²²⁵Ac-PSMA)-Trillium (BAY35663254) in mCRPC: Dose-escalation results of the phase 1 PanTHa study. Presented at: 2026 ASCO Genitourinary Cancers Symposium; February 26-28, 2026; San Francisco, CA. Abstract 19.

7. Agarwal N, Barata PD, Healy C, et al. MEVPRO-3: Phase III trial of mevrometostat plus enzalutamide (versus placebo plus enzalutamide) in metastatic castration-sensitive prostate cancer (mCRPC). Presented at: 2026 ASCO Genitourinary Cancers Symposium; February 26-28, 2026; San Francisco, CA. Abstract TPS284.

8. Tran B, Lewin JH, O’Haire S, et al. Initial results from CLIMATE, a prospective cohort study assessing the clinical utility of miR-371a-3[ (MiR-371) as a marker of minimal residual disease (MRD) in clinical stage 1 testicular germ cell tumor (TGCT): ANZUP 1906. Presented at: 2026 ASCO Genitourinary Cancers Symposium; February 26-28, 2026; San Francisco, CA. Abstract 586.

9. Pavel ME, Verslype C, Rocha P, et al. Obrixtamig (BI 764532) in patients (pts) with relapsed/refractory delta-like ligand 3 (DLL3)-high expressing extrapulmonary neuroendocrine carcinoma (epNEC): Dose expansion part of the phase II DAREON-5 trial. Presented at: 2026 ASCO Genitourinary Cancers Symposium; February 26-28, 2026; San Francisco, CA. Abstract TPS2.