KEY TAKEAWAYS
- Phase 3 KEYNOTE-905/EV-303 study aims to evaluate the efficacy and safety of perioperative pembro alone or in combination with EV compared with RC + PLND alone in cisplatin-ineligible or declining MIBC patients.
- In the phase 1b/2 KEYNOTE-869/EV-103 study, the combination of pembro and EV showed promising antitumor activity in cisplatin-ineligible patients with metastatic urothelial carcinoma.
- Eligibility criteria for enrollment in the KEYNOTE-905/EV-303 study include treatment-naive MIBC (T2-T4aN0M0 or T1-T4aN1M0) with Eastern Cooperative Oncology Group performance status score of 0-2 and predominant (≥50%) urothelial histology.
- Dual primary end points of the study are pathologic complete response and event-free survival, while secondary end points include overall survival, disease-free survival, pathologic downstaging rates, and safety and tolerability.
For MIBC, the gold standard treatment consists of neoadjuvant chemotherapy with cisplatin, followed by radical cystectomy and pelvic lymph node dissection (RC + PLND). There is a significant number of patients (pts) with MIBC who cannot receive cisplatin-based treatment.
Patients with metastatic urothelial cancer who could not receive cisplatin responded favorably to treatment with the PD-1 inhibitor pembro in combination with the nectin-4-directed antibody-drug conjugate EV in the phase 1b/2 KEYNOTE-869/EV-103 investigation. Patients with MIBC who are ineligible for or decline cisplatin-based treatment are the focus of the KEYNOTE-905 /EV-303 study (NCT03924895), a multicenter, open-label, randomized, phase 3 study evaluating the efficacy and safety of perioperative pembro alone or in combination with EV compared with RC + PLND alone.
About 857 adults with treatment-naive MIBC (T2-T4aN0M0 or T1-T4aN1M0) who are cisplatin ineligible or decline cisplatin-based treatment will be randomly assigned to arm A (neoadjuvant pembro 200 mg IV every 3 weeks [Q3W] up to 3 cycles followed by RC + PLND and adjuvant pembro 200 mg IV Q3W up to 14 cycles In arm C, pembro will be given on day 1 of the neoadjuvant phase, and EV will be given on day 1 and day 8 of the adjuvant phase.
Pathologic full response, determined by central pathologic assessment and event-free survival, are the two key end objectives. Overall survival, disease-free survival, pathologic downstaging rates, and safety and tolerability will serve as secondary end objectives. Worldwide (in Africa, Asia, Europe, and the Americas), enrollment is now ongoing.
Source: https://meetings.asco.org/2023-asco-gu-cancers-symposium/15312?presentation=216860#presentations
Clinical trial: https://clinicaltrials.gov/ct2/show/NCT03924895/
J Clin Oncol 41, 2023 (suppl 6; abstr TPS585)
