The FDA, in conjunction with decisions by regulatory agencies in Australia and Canada, granted accelerated approval to pembrolizumab in combination with lenvatinib for the treatment of certain women with advanced endometrial carcinoma, according to a press release from the agency.
The approval applies to women with disease that is neither microsatellite instability-high (MSI-H) nor mismatch repair-deficient (dMMR) who experienced progression after previous systemic therapy and are not candidates for surgery or radiation.
The move followed a review conducted through Project Orbis, an FDA collaboration with the Australian Therapeutic Goods Administration and Health Canada that establishes a framework for simultaneous evaluation of cancer drugs and decisions in the United States, Australia and Canada.
“We are pleased to be working alongside our Australian and Canadian colleagues to help make potentially life-changing treatments available to patients as quickly as possible while still ensuring the FDA’s high standards of safety and effectiveness,” acting FDA Commissioner Ned Sharpless, MD, said in the press release. “As Project Orbis expands, we look forward to welcoming additional international partnerships to collaborate with us in this important initiative as we work to help further serve the global patient community.”
The decision was based on results from the single-arm, multicenter KEYNOTE-146 trial, which enrolled 108 women with metastatic endometrial carcinoma that had progressed after at least one prior systemic therapy. Most of the women (n = 94) had tumors that were not MSI-H or dMMR, whereas 11 had tumors that were MSI-H and dMMR, and three had tumors with unknown MSI-H and dMMR status.
The women received lenvatinib (Lenvima, Eisai) at 20 mg orally in combination with pembrolizumab (Keytruda, Merck) at 200 mg IV every 3 weeks until progression or unacceptable toxicity.
Objective response rate and duration of response served as the primary endpoints of the study.
Results showed an ORR of 38.8% (95% CI, 29-49) among the 94 patients whose tumors were not MSI-H or dMMR. This included 10 complete responses (10.6%) and 26 partial responses (27.7%).
Median duration of response was not reached by data cutoff and 25 patients had a response of 6 months or longer.
Common adverse events included fatigue, hypertension, musculoskeletal pain, diarrhea, decreased appetite, hypothyroidism, nausea and stomatitis.
“In addition to the international collaboration with Australia and Canada, this review used the ‘Real-Time Oncology Review’ (RTOR) pilot program, which can streamline the submission of data prior to the completion and submission of the entire clinical application,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in the release. “RTOR, and its accompanying Assessment Aid, facilitated discussions among the regulatory agencies, expediting the approval in the three countries. These applications were approved 3 months prior to the FDA goal date.”