Rahway: Merck, known as MSD outside of the United States and Canada, has announced the U.S. Food and Drug Administration (FDA) has approved KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with Padcev (enfortumab vedotin-ejfv) for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (la/mUC) who are not eligible for cisplatin-containing chemotherapy.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. This marks the first time an anti-PD-1 therapy has been approved in combination with anantibody-drug conjugate in the U.S. in these patients.
The approval is based on data from the KEYNOTE-869 trial (also known as EV-103) dose escalation cohort, Cohort A and Cohort K, which was conducted in collaboration with Seagen and Astellas. The median follow-up time for the dose escalation cohort + Cohort A was 44.7 months (range, 0.7 to 52.4 months) and for Cohort K was 14.8 months (range, 0.6 to 26.2 months). In the combined efficacy analysis of the dose escalation cohort, Cohort A and Cohort K (n=121), KEYTRUDA in combination with enfortumab vedotin demonstrated an objective response rate (ORR) of 68% (95% CI: 58.7, 76.0), with complete and partial response rates of 12% and 55%, respectively. The median duration of response (DOR) for the dose escalation cohort + Cohort A was 22.1 months (range, 1.0+ to 46.3+ months) and for Cohort K was not reached (range, 1.2 to 24.1+ months).
“This approval is a major milestone in the treatment of patients with locally advanced or metastatic urothelial carcinoma because it is the first approved combination of an immunotherapy and an antibody-drug conjugate for these patients,” said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. “This expands the use of KEYTRUDA-based regimens to more patients with advanced urothelial carcinoma and demonstrates the value of collaboration in creating new combination approaches for patients in need of more options.”
Results from Cohort K were presented in a late-breaking session at the 2022 European Society for Medical Oncology Congress, and earlier results from dose escalation and Cohort A were published in the Journal of Clinical Oncology. The combination therapy was granted Breakthrough Therapy designation by the FDA in February 2020.
The accelerated approval designation granted is part of the FDA’s Accelerated Approval Program, which allows earlier approval of a medicine based on a surrogate endpoint if the medicine fills an unmet medical need for a serious condition. The ongoing Phase 3 EV-302/KEYNOTE-A39 trial evaluating the clinical benefit of KEYTRUDA in combination with enfortumab vedotin in patients with previously untreated advanced urothelial cancer is intended to serve as the U.S. confirmatory trial for the accelerated approval. It will also serve as the basis for global registration.