Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA
Standard of care for MIBC is neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy + pelvic lymph node dissection (RC + PLND). However, a substantial proportion of patients (pts) with MIBC are ineligible to receive cisplatin-based chemotherapy. In the phase 1b/2 KEYNOTE-869/EV-103 study, promising antitumor activity was shown in cisplatin-ineligible pts with metastatic urothelial carcinoma treated with the PD-1 inhibitor pembro combined with the nectin-4–directed antibody-drug conjugate EV. This multicenter, open-label, randomized, phase 3 KEYNOTE-905/EV-303 study (NCT03924895) is designed to evaluate the efficacy and safety of perioperative pembro alone or in combination with EV compared with RC + PLND alone in pts with MIBC who are ineligible for or decline cisplatin-based treatment.
Approximately 857 adults who are cisplatin ineligible or decline cisplatin-based treatment with treatment-naive MIBC (T2-T4aN0M0 or T1-T4aN1M0), have an Eastern Cooperative Oncology Group performance status score of 0-2, and have a predominant (≥50%) urothelial histology will be randomly assigned to arm A (neoadjuvant pembro 200 mg intravenously [IV] every 3 weeks [Q3W] up to 3 cycles followed by RC + PLND and adjuvant pembro 200 mg IV Q3W up to 14 cycles), arm B (RC + PLND followed by observation), or arm C (neoadjuvant EV 1.25 mg/kg + pembro 200 mg IV Q3W up to 3 cycles followed by RC + PLND and adjuvant EV + pembro up to 6 cycles and adjuvant pembro 200 mg IV Q3W up to 8 cycles). In both the neoadjuvant and adjuvant phases of arm C, pembro will be administered on day 1 and EV will be administered on days 1 and 8 of each cycle. Dual primary end points are pathologic complete response as assessed by central pathologic review and event-free survival. Secondary end points include overall survival, disease-free survival, pathologic downstaging rates, and safety and tolerability. Enrollment is ongoing in Africa, Asia, Europe, and North America. Clinical trial information: NCT03924895.