On April 20, 2026 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that the U.S. Food and Drug Administration (FDA) granted priority review for two supplemental Biologics License Applications (sBLA) for KEYTRUDA (pembrolizumab) and KEYTRUDA QLEX (pembrolizumab and berahyaluronidase alfa-pmph), Merck’s anti-PD-1 therapy, each in combination with Padcev (enfortumab vedotin-ejfv), for the treatment of patients with muscle-invasive bladder cancer (MIBC) who are eligible for cisplatin-based chemotherapy. The FDA set a Prescription Drug User Fee Act (PDUFA), or target action, date of August 17, 2026.
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If approved, these indications would expand the use of KEYTRUDA and KEYTRUDA QLEX, each in combination with Padcev, as the first perioperative treatments for patients with MIBC regardless of cisplatin eligibility and build on the previously approved indications of the combination for the treatment of patients with MIBC who are ineligible for cisplatin-based chemotherapy.
"Results from KEYNOTE-B15 challenge long-held expectations for patients with muscle-invasive bladder cancer," said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. "Even with curative-intent surgery and chemotherapy, patients still experience disease progression or limited survival. These data add to the growing body of evidence demonstrating that KEYTRUDA and KEYTRUDA QLEX, each in combination with Padcev, have the potential to reshape how we approach treatment for these patients and improve outcomes for people facing this aggressive disease."
The sBLAs are based on data from the Phase 3 KEYNOTE-B15 trial (also known as EV-304), which was conducted in collaboration with Pfizer and Astellas, which were presented at the recent American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary (GU) Cancers Symposium. The companies plan to share these results with regulatory authorities worldwide for potential regulatory filings.
KEYTRUDA plus Padcev is currently approved for the treatment of adult patients with locally advanced or metastatic urothelial cancer (la/mUC) in the U.S., the European Union (EU), Japan and several other countries around the world. KEYTRUDA plus Padcev is also approved in the U.S. for the treatment of adult patients with MIBC who are ineligible for cisplatin-based chemotherapy. KEYTRUDA as a monotherapy is also approved in the U.S., EU, Japan and other countries for the treatment of certain patients with la/mUC or a type of non-muscle-invasive bladder cancer (NMIBC).
KEYTRUDA plus Padcev has now demonstrated an overall survival (OS) benefit across three Phase 3 trials in bladder cancer. In addition to KEYNOTE-B15, these trials include previously announced positive results from KEYNOTE-905 for the treatment of patients with MIBC who are not eligible for or declined cisplatin-based chemotherapy and positive results from KEYNOTE-A39 for the treatment of adult patients with la/mUC. Three additional Phase 3 studies are currently evaluating KEYTRUDA across all stages of bladder cancer, including non-muscle-invasive, muscle-invasive and metastatic disease. Two of these studies are in MIBC including KEYNOTE-866 (NCT03924856) and KEYNOTE-992 (NCT04241185). KEYTRUDA is also being evaluated in combination with Bacillus Calmette-Guerin (BCG) in patients with NMIBC in KEYNOTE-676 (NCT03711032).
KEYNOTE-B15 is one of six Phase 3 studies of a KEYTRUDA-based regimen in an earlier stage of cancer to demonstrate an OS benefit. It was also the 15th positive pivotal trial for a KEYTRUDA-based regimen in earlier-stage cancers.
About KEYNOTE-B15/EV-304
KEYNOTE-B15, also known as EV-304, is an open-label, randomized Phase 3 trial (ClinicalTrials.gov, NCT04700124) evaluating perioperative KEYTRUDA in combination with Padcev and surgery (radical cystectomy and pelvic lymph node dissection) versus neoadjuvant chemotherapy (gemcitabine plus cisplatin) and surgery in patients with MIBC who are cisplatin-eligible. The trial enrolled 808 patients who were randomized to receive either:
Four cycles (each cycle length is 21 days) of neoadjuvant KEYTRUDA intravenous (IV) infusion plus enfortumab vedotin IV infusion, followed by surgery, followed by 13 cycles of adjuvant KEYTRUDA IV infusion plus five cycles of enfortumab vedotin IV infusion, or;
Four cycles (each cycle is 21 days) of standard of care neoadjuvant chemotherapy followed by surgery.
The primary endpoint is event-free survival (EFS), defined as the time from randomization to the first occurrence of the following events: radiographic disease progression precluding radical cystectomy and pelvic lymph node dissection, failure to undergo surgery in participants with residual disease, gross residual disease left behind at time of surgery, local or distant recurrence based on blinded independent central review or death due to any cause. The key secondary endpoints are OS and pathologic complete response rate.
About bladder cancer
In 2022, bladder cancer changed the lives of more than 600,000 people around the world. According to some clinical practice guidelines, about 25% of newly diagnosed bladder cancer cases are MIBC. The standard of care for patients with MIBC has been neoadjuvant cisplatin-based chemotherapy followed by surgery, which is shown to prolong survival. However, nearly half of patients who undergo this standard treatment experience recurrence.
(Press release, Merck & Co, APR 20, 2026, View Source [SID1234664543])