FDA Approves KEYTRUDA and KEYTRUDA QLEX in Combination with Padcev as Perioperative Treatment for Cisplatin-Ineligible Muscle-Invasive Bladder Cancer | iPharmaCenter

Merck announced that the U.S. Food and Drug Administration (FDA) has approved Keytruda (pembrolizumab) and Keytruda Qlex (pembrolizumab and berahyaluronidase alfa) in combination with Padcev (enfortumab vedotin) for the perioperative treatment of adults with muscle‑invasive bladder cancer (MIBC) who are ineligible for cisplatin‑based chemotherapy.

The regimen includes neoadjuvant therapy before surgery followed by adjuvant treatment after cystectomy.

These approvals mark the first PD‑1 inhibitor plus antibody‑drug conjugate (ADC) regimen approved for this patient population.

Approval Based on Phase 3 KEYNOTE‑905 (EV‑303) Data

The FDA decision is supported by results from the Phase 3 KEYNOTE‑905 trial (EV‑303), conducted in collaboration with Pfizer and Astellas. Presented at the European Society for Medical Oncology (ESMO) Congress, the data showed that perioperative KEYTRUDA plus Padcev achieved a statistically significant 60% reduction in the risk of event‑free survival (EFS) events compared with surgery alone.

After a median follow‑up of 25.6 months, patients receiving the combination had a hazard ratio (HR) for EFS of 0.40, with median EFS not yet reached versus 15.7 months in the surgery‑alone group.

The combination also demonstrated a 50% improvement in overall survival (OS) versus surgery alone, along with a higher pathologic complete response rate of 57.1% compared with 8.6% for surgery alone.

The effectiveness of Keytruda Qlex for its approved indications is supported by data from studies with Keytruda and comparative pharmacokinetic, efficacy, and safety data from study MK‑3475A‑D77.

Safety Information

Keytruda Qlex is contraindicated in patients with known hypersensitivity to berahyaluronidase alfa, hyaluronidase, or any excipients. Immune‑mediated adverse reactions, which may be severe or fatal, can occur in any organ system or simultaneously affect multiple organ systems.

About the KEYNOTE‑905 Trial

KEYNOTE‑905 (NCT03924895) is an open‑label, randomized, multi‑arm, Phase 3 study comparing perioperative Keytruda with or without Padcev versus surgery alone in adults with MIBC who were ineligible for or declined cisplatin‑based chemotherapy. The study enrolled 344 patients randomized 1:1.

Experimental arm (n=170): Neoadjuvant pembrolizumab 200 mg IV (Day 1) plus enfortumab vedotin 1.25 mg/kg IV (Days 1 and 8) every 21 days for three cycles, followed by surgery and adjuvant treatment for up to 14 cycles of pembrolizumab and six cycles of enfortumab vedotin.

Control arm (n=174): Immediate radical cystectomy and pelvic lymph node dissection alone.

About Keytruda and Keytruda Qlex

Keytruda (pembrolizumab) is an anti–PD‑1 therapy that enhances the body’s immune response to help detect and fight tumor cells by blocking the PD‑1/PD‑L1 and PD‑L2 interaction, thus activating T lymphocytes.

Merck’s global clinical program includes over 1,600 trials exploring Keytruda across numerous cancers and treatment settings.

Keytruda Qlex (pembrolizumab and berahyaluronidase alfa‑pmph) is a fixed‑dose combination for subcutaneous use. The formulation enables subcutaneous delivery of pembrolizumab through the action of berahyaluronidase alfa, which facilitates dispersion and absorption. It is administered as an injection into the thigh or abdomen (avoiding the 5 cm area around the navel), either over one minute every three weeks or over two minutes every six weeks.