The Food and Drug Administration (FDA) has accepted for Priority Review the supplemental Biologics License Application (sBLA) for pembrolizumab (Keytruda®) as adjuvant treatment of patients with renal cell carcinoma (RCC) at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.
The sBLA for RCC is supported by data from the pivotal phase 3 KEYNOTE-564 trial (ClinicalTrials.gov Identifier: NCT03142334), which evaluated the efficacy and safety of pembrolizumab monotherapy for the adjuvant treatment of 994 adults with RCC who have undergone nephrectomy and who have intermediate-high, high risk, or M1 no evidence of disease (M1 NED) RCC with clear cell component. Patients were randomly assigned 1:1 to receive either pembrolizumab 200mg intravenously (IV) on day 1 of each 3-week cycle for up to 17 cycles or placebo. The primary endpoint was disease-free survival (DFS); key secondary endpoints included overall survival (OS) and safety.
At a median follow-up of 24 months, results showed that treatment with pembrolizumab met the primary endpoint reducing the risk of disease recurrence or death by 32% vs placebo (hazard ratio [HR], 0.68; 95% CI, 0.53-0.87; P =.001); the median DFS was not reached in either treatment arm. At 24 months, the estimated DFS rate was 77.3% with pembrolizumab vs 68.1% with placebo. The median OS data was not reached at the time of analysis; but at month 24, the estimated OS rate was 96.6% with pembrolizumab and 93.5% with placebo, corresponding to a 46% reduction. A Prescription Drug User Fee Act (PDUFA) target date of December 10, 2021 has been set for the application.
The FDA has also accepted for review the sBLA for pembrolizumab as a single agent for the treatment of patients with advanced endometrial carcinoma that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
The sBLA for advanced endometrial carcinoma was based on overall response data from cohorts D and K of the phase 2 KEYNOTE-158 trial (ClinicalTrials.gov Identifier: NCT02628067), which evaluated pembrolizumab in patients with multiple types of advanced solid tumors. Cohort K included 79 patients with MSI-H endometrial carcinoma and cohort D included 11 patients with MSI-H endometrial carcinoma. Patients received pembrolizumab 200mg fixed dose IV every 3 weeks. Findings from the trial will be presented at the European Society for Medical Oncology Congress 2021. A PDUFA target date of March 28, 2022 has been set for the application.
- FDA grants Priority Review to Merck’s supplemental Biologics License Application for Keytruda® (pembrolizumab) as adjuvant therapy in certain patients with renal cell carcinoma (RCC) following surgery. News release. Merck & Co., Inc. Accessed August 10, 2021. https://www.businesswire.com/news/home/20210810005542/en/FDA-Grants-Priority-Review-to-Merck%E2%80%99s-Supplemental-Biologics-License-Application-for-KEYTRUDA%C2%AE-pembrolizumab-as-Adjuvant-Therapy-in-Certain-Patients-With-Renal-Cell-Carcinoma-RCC-Following-Surgery.
- FDA accepts application for Merck’s Keytruda® (pembrolizumab) as single agent for certain patients with MSI-H/dMMR advanced endometrial carcinoma. News release. Merck & Co., Inc. Accessed August 10, 2021. https://www.businesswire.com/news/home/20210810005544/en/FDA-Accepts-Application-for-Merck%E2%80%99s-KEYTRUDA%C2%AE-pembrolizumab-as-Single-Agent-for-Certain-Patients-With-MSI-HdMMR-Advanced-Endometrial-Carcinoma.
- Choueiri TK, Tomczak P, Park SH, et al. Pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for patients with renal cell carcinoma: Randomized, double-blind, phase III KEYNOTE-564 study. J Clin Oncol. Published online June 16, 2021. doi: 10.1200/JCO.2021.39.15_suppl.LBA5