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. 


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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.

References

  1. 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.
  2. 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
  3. 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