(UroToday.com) On the second day of the American Society for Clinical Oncology (ASCO) Genitourinary Cancer Symposium 2023 focussing on urothelial cancer, the Trials in Progress Poster Session B included a presentation from Dr. Andrea Necchi on the KETNOTE-905/EV-303 trial, a phase III trial of perioperative pembrolizumab either alone or with enfortumab vedotin (EV) for patients with muscle-invasive bladder cancer (MIBC).
For patients with MIBC, one of the standard of care treatment options is neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy + pelvic lymph node dissection (RC + PLND). Unfortunately, a substantial proportion of patients with MIBC are ineligible or unwilling to receive cisplatin-based chemotherapy. Thus, there is an ongoing need for alternative treatment paradigms. In the phase 1b/2 KEYNOTE-869/EV-103 study, combination therapy with the PD-1 inhibitor pembrolizumab combined with the nectin-4–directed antibody-drug conjugate enfortumab vedotin demonstrated promising antitumor activity in cisplatin-ineligible patients with metastatic urothelial carcinoma. To further evaluate this treatment approach and specifically evaluate the efficacy and safety of perioperative pembrolizumab alone or in combination with enfortumab vedotin compared with RC + PLND alone in patients with MIBC who are ineligible for or decline cisplatin-based treatment, these authors designed the multicenter, open-label, randomized, phase 3 KEYNOTE-905 / EV-303 study (NCT03924895).
The authors are recruiting a target of approximately 857 adults with treatment-naive MIBC (T2-T4aN0M0 or T1-T4aN1M0) who are cisplatin ineligible or decline cisplatin-based treatment. Eligible patients are further required to have an Eastern Cooperative Oncology Group performance status score of 0-2 and have a predominant (≥50%) urothelial histology.
Once enrolled, patients will be randomly assigned to arm A (neoadjuvant pembrolizumab 200 mg intravenously [IV] every 3 weeks [Q3W] up to 3 cycles followed by RC + PLND and adjuvant pembrolizumab 200 mg IV Q3W up to 14 cycles), arm B (RC + PLND followed by observation), or arm C (neoadjuvant enfortumab vedotin 1.25 mg/kg + pembrolizumab 200 mg IV Q3W up to 3 cycles followed by RC + PLND and adjuvant enfortumab vedotin + pembrolizumab up to 6 cycles and adjuvant pembrolizumab 200 mg IV Q3W up to 8 cycles). In both the neoadjuvant and adjuvant phases of arm C, pembrolizumab will be administered on day 1 and enfortumab vedotin will be administered on days 1 and 8 of each cycle.
The study's dual primary endpoints are pathologic complete response as assessed by central pathologic review and event-free survival. Additional secondary endpoints include overall survival, disease-free survival, pathologic downstaging rates, and safety and tolerability. Currently, enrollment is ongoing in Africa, Asia, Europe, and North America.
Presented by: Andrea Necchi, MD | Vita-Salute San Raffaele University; Department of Medical Oncology, IRCCS San Raffaele Hospital and Scientific Institute