Perioperative EV Plus Pembro vs. Chemo for MIBC: KEYNOTE-B15/EV-304 Results

In cisplatin-eligible patients with muscle-invasive bladder cancer (MIBC), the standard of care is neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy + pelvic lymph node dissection (RC+PLND). However, up to 50% of patients will experience disease recurrence or progression after treatment. Patients with metastatic urothelial cancer may utilize pembro or EV monotherapy (mUC). Positive anticancer activity and a manageable safety profile were also observed in the phase 1/2 KEYNOTE-869/EV-103 study of first-line combination therapy with EV + pembro in cisplatin-ineligible pts with mUC.

To assess the efficacy and safety of perioperative EV + pembro against neoadjuvant cisplatin-based treatment in cisplatin-eligible pts with MIBC, the KEYNOTE-B15/EV-304 research (NCT04700124) is conducting an open-label, multicenter, randomized phase 3 investigation. Patients who meet the inclusion criteria will have the nonmetastatic disease (N1, M0) confirmed by blinded independent central review (BICR), an ECOG performance status of 0-1, no prior systemic therapy for MIBC, and will agree to undergo curative RC+PLND. In addition, histologically confirmed UC/MIBC (T2-T4aN0M0 or T1-T4aN1M0) with predominant urothelial histology (50%) will be considered.
Approximately 784 patients will be randomly assigned to either Arm A (4 cycles of neoadjuvant etoposide + pembro, followed by resection + PLND, followed by 5 cycles of adjuvant etoposide + thirteen cycles of adjuvant pembro) or Arm B (four cycles of neoadjuvant chemotherapy [gemcitabine + cisplatin], followed by RC + PLND, followed by observation). Pembro 200 mg + EV 1.25 mg/kg will be given intravenously on cycle day 1 (pembro + EV) and cycle day 8 (EV) as a neoadjuvant and adjuvant, respectively. On days 1 (gemcitabine + cisplatin) and 8 (gemcitabine) of each cycle, 1000 mg/m2 + cisplatin 70 mg/m2 Q3W is administered as neoadjuvant chemotherapy. Disease stage (T2N0, T3, or T4aN0 versus T1, T2, or T4aN1), PD-L1 combined positive score (10 versus 10), and geographic location are used as stratification criteria (United States vs. European Union vs most of the world).
At least 6 weeks before and after a cystectomy, the patient will have CT (preferred) or MRI imaging. After a cystectomy, imaging will be performed every 12 weeks for the first year, then every 24 weeks for the second, and every 48 weeks for the third and beyond. Negative side effects (AEs) will be tracked for the trial’s duration and 30 days after treatment has stopped (90 days for serious AEs). Complete pathologic response rate and BICR-defined event-free survival are the key end objectives. Survival time, disease-free survival, pathologic downstaging rate, adverse events, and patient satisfaction are secondary goals. Participation in KEYNOTE-B15/EV-304 is open to people from all over the world. As of 2021, the American Society of Clinical Oncology, Inc. Used it legally again. The 2021 Annual Conference of the American Society of Clinical Oncology approved this abstract.

Source: https://meetings.asco.org/abstracts-presentations/216863

Clinical trial: https://clinicaltrials.gov/ct2/show/NCT04700124

Hoimes C, Loriot Y, Nishiyama H, Kataria R, Moreno B, Galsky M. Perioperative enfortumab vedotin (EV) plus pembrolizumab (pembro) versus chemotherapy in cisplatin-eligible patients (pts) with muscle-invasive bladder cancer (MIBC): Phase 3 KEYNOTE-B15/EV-304. J Clin Oncol 41, 2023 (suppl 6; abstr TPS588)