FDA approves combo therapy for Cisplatin-ineligible muscle-invasive bladder cancer patients

The approvals target adult MIBC patients who are ineligible for cisplatin-based chemotherapy

Pharma major Merck has announced a major breakthrough for patients with muscle-invasive bladder cancer (MIBC).

The US FDA has approved KEYTRUDA (pembrolizumab) and KEYTRUDA QLEX (pembrolizumab plus berahyaluronidase alfa-pmph) in combination with Padcev (enfortumab vedotin-ejfv) for neoadjuvant treatment prior to surgery and continued adjuvant therapy afterward, marking the first PD-1 inhibitor plus antibody-drug conjugate (ADC) regimen for this population.

The approvals target adult MIBC patients who are ineligible for cisplatin-based chemotherapy, addressing a critical unmet need in a group with historically limited treatment options, according to the company known as MSD outside North America.

The decision is based on results from the Phase 3 KEYNOTE-905 trial (EV-303), conducted with Pfizer and Astellas. Patients receiving the KEYTRUDA–Padcev combo saw a 60% reduction in the risk of event-free survival events compared to surgery alone and a 50% improvement in overall survival. The combination also produced a pathologic complete response in 57% of patients, versus just 9% with surgery alone.

“These approvals could be practice-changing for patients who previously had no options beyond surgery,” said Dr Matthew Galsky, KEYNOTE-905 study investigator at Mount Sinai Tisch Cancer Center. “Half of MIBC patients face cancer recurrence even after bladder removal, and many cannot receive cisplatin. This therapy offers hope where there was none.”

Merck emphasizes flexibility in administration, allowing patients to receive immunotherapy intravenously or subcutaneously. “Our commitment to patients drives innovation,” said Dr Marjorie Green, senior VP, Merck Research Laboratories. “We are proud to provide new, life-saving options for those in need.”

KEYTRUDA and KEYTRUDA QLEX carry potential for serious immune-mediated reactions affecting multiple organs and systems. Severe or fatal infusion-related reactions are possible, and use during pregnancy may cause fetal harm. Patients should be carefully monitored, with corticosteroids administered for adverse reactions when appropriate.

The open-label, multi-arm Phase 3 trial enrolled 344 cisplatin-ineligible MIBC patients, comparing perioperative KEYTRUDA—with or without Padcev—against surgery alone. Patients received three cycles of neoadjuvant therapy before cystectomy, followed by up to 14 cycles of adjuvant KEYTRUDA and six cycles of adjuvant Padcev.

So what are the next steps? With FDA approval, KEYTRUDA plus Padcev is poised to become a new standard of care for cisplatin-ineligible MIBC patients, offering a survival advantage and new hope for a population that has gone decades without treatment innovation.