Merck: FDA approves KEYTRUDA and KEYTRUDA QLEX with Padcev for perioperative MIBC
- Approval covers KEYTRUDA or KEYTRUDA QLEX each combined with Padcev as neoadjuvant therapy and continued post‑cystectomy, regardless of cisplatin eligibility.
- Approval based on Phase 3 KEYNOTE‑B15 (EV‑304), a trial enrolling 808 patients conducted with Pfizer and Astellas.
- KEYTRUDA plus Padcev reduced the risk of event‑free survival events by 47% versus neoadjuvant gemcitabine‑cisplatin and surgery (HR=0.53; 95% CI, 0.41–0.70; p<0.0001).
- KEYTRUDA plus Padcev reduced risk of death by 35% versus neoadjuvant gemcitabine‑cisplatin and surgery (HR=0.65; 95% CI, 0.48–0.89; p=0.0029).
Regulatory update
The FDA approved KEYTRUDA (pembrolizumab) and KEYTRUDA QLEX (pembrolizumab with berahyaluronidase alfa‑pmph), each in combination with Padcev (enfortumab vedotin‑ejfv), as neoadjuvant treatment and continued adjuvant treatment after cystectomy for adults with muscle‑invasive bladder cancer (MIBC). The approvals apply regardless of cisplatin eligibility.
Trial basis
The approvals were based on data from the Phase 3 KEYNOTE‑B15 trial (EV‑304), conducted in collaboration with Pfizer and Astellas, which enrolled 808 patients. They expand an earlier indication based on Phase 3 KEYNOTE‑905 (EV‑303) that covered cisplatin‑ineligible patients.
Key efficacy results
In KEYNOTE‑B15, perioperative KEYTRUDA plus Padcev versus neoadjuvant gemcitabine‑cisplatin and surgery showed a 47% reduction in risk of EFS events (HR=0.53; 95% CI, 0.41–0.70; p<0.0001), with 87/405 (21%) versus 146/403 (36%) events. Median EFS was not reached for the combination versus 48.5 months for chemotherapy. The regimen also reduced risk of death by 35% (HR=0.65; 95% CI, 0.48–0.89; p=0.0029), with 69/405 (17%) versus 99/403 (25%) deaths; median OS was not reached for either arm. Pathologic complete response rate was 55.8% versus 32.5% in favor of KEYTRUDA plus Padcev (p<0.0001).
KEYTRUDA QLEX data linkage
The effectiveness of KEYTRUDA QLEX is supported by the KEYTRUDA studies plus bridging data from MK‑3475A‑D77 comparing pharmacokinetics, efficacy and safety between KEYTRUDA QLEX and KEYTRUDA.
Source: Merck