FULL APPROVAL

FDA approves Merck's Keytruda plus Padcev for muscle-invasive bladder cancer

The approval, weeks ahead of its August 17 PDUFA date, rests on a 47% reduction in disease progression or death versus chemotherapy before and after surgery.

By AppliedXLJuly 10, 2026Trial NCT04700124

Executive Summary

The FDA approved a checkpoint-inhibitor-plus-antibody-drug-conjugate regimen for perioperative use in the larger, cisplatin-eligible segment of muscle-invasive bladder cancer, arriving ahead of its target review date.
The trial behind the approval showed the combination cut the risk of disease progression, recurrence, or death nearly in half and reduced the risk of death by more than a third compared with the chemotherapy-and-surgery standard, with a higher rate of pathologic complete response at surgery.
This marks the third Phase 3 trial in bladder cancer where the same combination has shown an overall survival benefit, extending a consistent result across successive patient populations rather than resting on a single trial.
No other PD-1 inhibitor paired with an antibody-drug conjugate has reached approval in this indication, leaving the standard-of-care comparison as neoadjuvant chemotherapy rather than a rival combination regimen.

What was approved

Merck announced on July 10, 2026 that the FDA approved Keytruda (pembrolizumab) and Keytruda Qlex (pembrolizumab and berahyaluronidase alfa-pmph), each in combination with Padcev (enfortumab vedotin-ejfv), as neoadjuvant treatment before cystectomy and continued adjuvant treatment after surgery in adult patients with muscle-invasive bladder cancer. The approval covers patients eligible for cisplatin-based chemotherapy, the larger of the two MIBC eligibility segments, and builds on a 2025 approval of the same regimen for patients ineligible for cisplatin. The FDA had set a target action date of August 17, 2026 after granting priority review in April 2026; the decision landed roughly five weeks ahead of that date. FDA+1

The result: EFS, OS, and pCR

The approval rests on the Phase 3 KEYNOTE-B15 trial (also known as EV-304, NCT04700124), which enrolled 808 patients across the United States, Japan, France, Germany, China, South Korea, and other countries and completed on October 27, 2025. Perioperative Keytruda plus Padcev reduced the risk of event-free survival events, disease progression, recurrence, or death, by 47% versus neoadjuvant gemcitabine and cisplatin (HR=0.53, 95% CI 0.41-0.70; p<0.0001; 87 of 405 patients versus 146 of 403). Median EFS was not reached in the combination arm versus 48.5 months for chemotherapy. The combination also reduced the risk of death by 35% (HR=0.65, 95% CI 0.48-0.89; p=0.0029; 69 of 405 versus 99 of 403), and improved the pathologic complete response rate to 55.8% versus 32.5% for chemotherapy (p<0.0001). NCT04700124+1

Third positive trial in the class

Dr. Marjorie Green, Merck's senior vice president and head of oncology, global clinical development, said in April that KEYNOTE-B15 results "challenge long-held expectations for patients with muscle-invasive bladder cancer" given that many still progress or die despite curative-intent surgery and chemotherapy. The July approval marks the third Phase 3 trial, alongside KEYNOTE-905 and KEYNOTE-A39, in which Keytruda plus Padcev has shown an overall survival benefit in bladder cancer, extending the same combination across the cisplatin-ineligible MIBC, cisplatin-eligible MIBC, and metastatic urothelial carcinoma settings. Merck said the safety profile in KEYNOTE-B15 was consistent with the known profiles of the two drugs. FDA+1

The competitive field

No other PD-1 inhibitor combined with an antibody-drug conjugate has reached approval in muscle-invasive bladder cancer, and no peer trial in this indication shares both the PD-1 target and the antibody-drug-conjugate modality of this regimen. The nearest activity in the indication comes from other modalities: Janssen's TAR-210 and TAR-200 programs targeting FGFR3 and intravesical delivery, and Astellas's ongoing EV-309 trial (NCT07566156) comparing enfortumab vedotin plus pembrolizumab against chemoradiotherapy rather than surgery. With the chemotherapy-and-surgery standard now facing a combination that beat it on three separate endpoints in KEYNOTE-B15, the comparison other MIBC programs will be measured against has shifted from surgery-plus-chemotherapy alone to this regimen's disclosed effect sizes. FDA

This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.