Merck Gains FDA Approval for IV and Subcutaneous Pembrolizumab Each with Enfortumab Vedotin in Muscle Invasive Bladder Cancer

Merck's simultaneous approval of two pembrolizumab formulations in the same perioperative indication creates an immediate fill-finish and device-integration decision point for manufacturing and QA teams supporting oncology portfolios. On July 10, 2026, the FDA approved both pembrolizumab IV (Keytruda) and pembrolizumab with berahyaluronidase alfa-pmph subcutaneous (Keytruda Qlex), each in combination with enfortumab vedotin-ejfv (Padcev, Astellas Pharma), as neoadjuvant treatment followed by adjuvant therapy after cystectomy for adults with muscle invasive bladder cancer (MIBC) who are candidates for surgery, expanding the prior approval beyond cisplatin-ineligible patients to all eligible candidates.

Efficacy data from KEYNOTE-B15/EV-304 (NCT04700124) underpins the label. The open-label, randomized, active-controlled trial enrolled 808 previously untreated MIBC patients eligible for radical cystectomy with pelvic lymph node dissection. The perioperative pembrolizumab plus enfortumab vedotin-ejfv arm demonstrated statistically significant improvements over neoadjuvant gemcitabine and cisplatin in both event-free survival (EFS hazard ratio 0.53 [95% CI: 0.41, 0.70]; p<0.0001) and overall survival (OS hazard ratio 0.65 [95% CI: 0.48, 0.89]; p=0.0029), with median EFS not reached in the experimental arm versus 48.5 months in the comparator arm.

For QA directors and regulatory leads, the prescribing information carries a layered warning profile requiring close attention at the site level. Pembrolizumab labeling includes precautions for immune-mediated adverse reactions, infusion-related reactions, allogeneic hematopoietic stem cell transplantation complications, and embryo-fetal toxicity. Enfortumab vedotin-ejfv labeling adds skin reactions, hyperglycemia, pneumonitis/interstitial lung disease, peripheral neuropathy, ocular disorders, and infusion site extravasation, each requiring documented risk communication and pharmacovigilance processes aligned with 21 CFR Part 211 and post-approval commitments.

The dual-formulation launch introduces concrete operational complexity. The IV regimen specifies pembrolizumab at 200 mg every 3 weeks or 400 mg every 6 weeks across neoadjuvant and adjuvant phases, with enfortumab vedotin-ejfv dosed on Days 1 and 8 of a 21-day cycle. Administration sequencing is defined: pembrolizumab must follow enfortumab vedotin-ejfv when co-administered on the same day. Contract and in-house fill-finish sites supporting both formulations will need to assess device compatibility, cold-chain handling differences, and batch release workflows for the subcutaneous presentation under current GMP requirements.

The review was conducted under Project Orbis, the FDA Oncology Center of Excellence's framework for concurrent international oncology submissions, signaling that regulatory dossiers for partner agencies may already be in review, a timeline consideration for sites planning commercial-scale process validation across markets.

Full prescribing information for Keytruda, Keytruda Qlex, and Padcev will be posted on Drugs@FDA, providing the definitive reference for labeling-driven manufacturing and quality system updates.

Source: FDA Drugs@FDA / What's New: Drugs RSS Feed, July 10, 2026.