Key Trial Data Presented at 2026 ASCO Genitourinary Cancers Symposium

The 2026 Genitourinary Cancers Symposium (ASCO GU), held from February 26 through 28, 2026, in San Francisco, California, featured notable presentations including data from the first interim analysis of the phase 3 LITESPARK-022 trial (NCT05239728), results from the final analysis of the SunRISE-2 study (NCT04658862), findings from the phase 3 KEYNOTE-B15/EV-304 trial (NCT04700124) and final data from the phase 3 EORTC 1333/PEACE-3 trial (NCT02194842).

In LITESPARK-022, belzutifan plus pembrolizumab led to a significant DFS benefit vs pembrolizumab monotherapy (HR, 0.72; 95% CI, 0.59-0.87; P = .0003). Findings from LITESPARK-022 supported the February 2026 supplemental new drug applications (sNDAs) seeking the approval of the HIF-2α inhibitor belzutifan (Welireg) in combination with pembrolizumab or berahyaluronidase alfa-pmph (Keytruda Qlex) for the adjuvant treatment of adult patients with renal cell carcinoma (RCC) with a with a clear cell component at an increased risk of recurrence following nephrectomy. These sNDAs are under priority review by the FDA.

LITESPARK-022 was the first trial to build on adjuvant pembrolizumab (Keytruda) in this patient population. The 2 things to remember are the risks of anemia and hypoxia, as well as familiarity with dose reduction, dose interruption, and, most importantly, erythropoiesis-stimulating agent use, as well as blood transfusion if needed.

In KEYNOTE B-15, enfortumab vedotin plus pembrolizumab produced a notable EFS benefit vs cisplatin/gemcitabine (HR, 0.53; 95% CI, 0.41-0.70; P < .001). Results from KEYNOTE-B15 showed remarkable consistency with those from the phase 3 KEYNOTE-905 study (NCT03924895), particularly in terms of the pathological CR rate end point. Two phase 3 studies now show pretty consistent findings, highlighting both the reproducibility and generalizability of results that have been seen with enfortumab vedotin-ejfv (Padcev) plus pembrolizumab across all clinical settings.

SunRISE-2 did not meet its primary end point of improving bladder-intact event-free survival (BI-EFS) with the gemcitabine intravesical system (Gem-iDRS; Inlexzo; previously TAR-200) plus cetrelimab (JNJ-63723283). In both arms, the estimates with chemoradiotherapy and experimental therapy at 1 year were particularly promising and higher than expected. Chemoradiotherapy performed better than expected when the study was initially conceived. However, Gem-iDRS and cetrelimab provided complete response (CR) and BI-EFS outcomes that were still compelling and warrant further investigation in patients with muscle-invasive bladder cancer (MIBC) not receiving radical cystectomy.

Enzalutamide plus radium-223 displayed superior OS compared with enzalutamide alone (HR, 0.76; 95% CI, 0.60-0.96; one-sided log-rank P = .0096) in the PEACE-3 study.

The phase 3 LITESPARK-011 trial (NCT04586231) is comparing lenvatinib (Lenvima) plus belzutifan with cabozantinib (Cabometyx) following previous PD-(L)1 therapy, with progression-free survival magnitude and patient-reported outcomes expected to be key to defining practice impact.