FDA Approval Summary: Pembrolizumab plus Lenvatinib for Endometrial Carcinoma, a Collaborative International Review under Project Orbis.

Abstract

On September 17, 2019, FDA granted accelerated approval to pembrolizumab plus lenvatinib for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) and who have disease progression following prior systemic therapy but are not candidates for curative surgery or radiation. The submission and review of this application was conducted through an FDA Oncology Center of Excellence initiative named Project Orbis whereby the FDA, the Australian Therapeutic Goods Administration, and Health Canada were able to simultaneously review and collaborate, rendering simultaneous approval decisions in all countries. Accelerated approval of the pembrolizumab plus lenvatinib combination was based on a single-arm trial of 94 patients, with previously treated metastatic endometrial cancer whose tumors were not MSI-H/dMMR. Efficacy was demonstrated on the basis of an objective response rate of 38.3% (95% confidence interval, 28.5%-48.9%) with 10 complete responses (10.6%) accompanied by supportive durations of response. Trials to confirm clinical benefit of this combination are ongoing. Here, we summarize the benefit-risk analysis supporting accelerated approval of the pembrolizumab plus lenvatinib combination and describe the methodology for the first Project Orbis review.

• Authors: Shaily Arora, Sanjeeve Balasubramaniam, Wei Zhang, Lijun Zhang, Rajeshwari Sridhara, Dianne Spillman, Jaigi P Mathai, Bradley Scott, Sarah J Golding, Michael Coory, Richard Pazdur, Julia A Beaver
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 26 Issue 19 Pg. 5062-5067 (10 01 2020) ISSN: 1557-3265 [Electronic] United States
• PMID: 32295834 (Publication Type: Journal Article, Review)
• Copyright: ©2020 American Association for Cancer Research.

Chemical References

• Antibodies, Monoclonal, Humanized
• Phenylurea Compounds
• Quinolines
• pembrolizumab
• lenvatinib

Topics

• Antibodies, Monoclonal, Humanized (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Australia (epidemiology)
• Canada (epidemiology)
• Drug Approval
• Endometrial Neoplasms (drug therapy, genetics, pathology)
• Female
• Humans
• Microsatellite Instability
• Phenylurea Compounds (therapeutic use)
• Quinolines (therapeutic use)
• United States
• United States Food and Drug Administration