FDA Accepts sBLA for Padcev, Keytruda Combo for Urothelial Cancer


The combination includes an antibody-drug conjugate with an immunotherapy to treat patients with advanced bladder cancer. The PDUFA action date is April 21, 2023.

The FDA has accepted for priority review the supplemental biologics license applications for (sBLAs) for Seagen and Astellas Pharma’s for metastatic urothelial cancer combination treatment Padcev (enfortumab vedotin-ejfv) and Merck’s Keytruda (pembrolizumab). The new combo would be to treat patients with locally advanced or metastatic urothelial cancer (la/mUC) who are not eligible to receive cisplatin-containing chemotherapy.

The respective applications are intended to expand both labels for Padcev and Keytruda. The FDA set a Prescription Drug User Fee Act (PDUFA) goal date for each application of April 21, 2023.

Eliav Barr, M.D.

Eliav Barr, M.D.

“Despite advancements in treatment options, approximately half of advanced bladder cancer patients in the US are ineligible for cisplatin-based chemotherapy, and these patients need new options,” Eliav Barr, M.D., senior vice president, head of Global Clinical Development and chief medical officer at Merck Research Laboratories, said in a press release. “We are encouraged by the investigational results of the combination of Padcev and Keytruda for this patient population and are fully committed to work to bring this new approach forward to patients.”

The combination therapy was granted breakthrough therapy designation by the FDA in February 2020.

The respective sBLAs are supported by efficacy and safety data from the phase 1b/2 EV-103 trial (KEYNOTE-869) were published in the Journal of Clinical Oncology. Results from Cohort K were presented in a late-breaking session at the 2022 European Society for Medical Oncology (ESMO) Congress.

The study found that the combination provides a durable option for patients whose disease may not be suitable for treatment with a cisplatin-based chemotherapy. Results demonstrated a 64.5% confirmed objective response rate (ORR) by blinded independent central review, the primary endpoint of Cohort K, with 10.5% of patients experiencing a complete response and 53.9% of patients experiencing a partial response.

Median overall survival of patients treated with the combination was 22.3 months. Among patients treated with enfortumab vedotin, median progression free survival was 8.0 months, and median overall survival was 21.7 months.

All-grade treatment-related adverse events for the combination were skin reactions (67.1%), peripheral neuropathy (60.5%), ocular disorders (dry eye, blurred vision and corneal disorders) (26.3%), hyperglycemia (14.5%) and infusion-related reactions (3.9%).

“Urothelial cancer, the most common type of bladder cancer, is associated with poor survival in the advanced stage,” Marjorie Green, MD, senior vice president and head of Late-Stage Development, Seagen, said in a press release. “The investigational results from our clinical development program support the combination of Padcev and Keytruda as a potential treatment for this patient population.”

Padcev includes a Boxed Warning for serious skin reactions.

Seagen, Astellas and Merck are further investigating the two medications in the ongoing phase 3 EV-302 (KEYNOTE-A39), evaluating the clinical benefit in patients with previously untreated advanced urothelial cancer. The trial is intended to serve as the confirmatory trial for the potential accelerated approval in the United States and serve as the basis for global registration.

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