FDA Grants Priority Review to BLA for Adjuvant Pembrolizumab in Certain Cases of RCC After Surgery

A priority review to a biologics license application has been granted by the FDA for adjuvant pembrolizumab in certain populations of patients with renal cell carcinoma who have undergone surgery.

The FDA has granted priority review to a supplemental biologics license application (sBLA) for adjuvant pembrolizumab (Keytruda) in patients with an intermediate-high or high risk of recurrence following nephrectomy or nephrectomy and resection of metastatic lesions, according to a press release from drug developer Merck.1

The sBLA is based on data from the pivotal phase 3 KEYNOTE-564 study (NCT03142334), the results of which were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.2 Findings from the study indicated that, after a median follow up of 24.1 months, patients who were treated with pembrolizumab experienced a 12-month disease-free survival (DFS) rate of 85.7% and a 24-month rate of 77.3% vs 76.2% and 68.1%, respectively, in the placebo arm (HR, 0.68; 95% CI, 0.53-0.87; P = .0010). Moreover, pembrolizumab yielded a 12-month overall survival rate of 98.6% and a 24-month rate of 96.6% compared with 98.0% and 93.5%, respectively, in the placebo group (HR, 0.54; 95% CI, 0.30-0.96; P = .0164). The improvement in DFS vs placebo was considered significant and clinically meaningful.

The FDA set the Prescription Drug User Free Act or target action date to be December 10, 2021.

“The acceptance of our application demonstrates the progress we are making in earlier lines and earlier stages of certain cancers across our oncology portfolio,” Scot Ebbinghaus, MD, vice president of clinical research at Merck Research Laboratories, said in a press release. “We look forward to working with the FDA towards the goal of bringing the first adjuvant immunotherapy option to appropriate patients with renal cell carcinoma in the U.S.”

The study enrolled 994 patients who were randomized 1:1 to receive either 200 mg of pembrolizumab (n = 496) once every 3 weeks for 1 year or placebo (n = 498) with the same dosing schedule. The study enrolled patients with histologically confirmed clear cell RCC who had underwent nephrectomy 12 weeks or less prior to randomization. Additionally, prior systemic therapies were not allowed. Patients were required to have an ECOG performance status of 0 or 1, as well as a tissue sample for PD-L1 assessment.

The primary end point for the study is DFS per investigator assessment, with a key secondary end point of OS as well as safety.

In terms of safety, 32.4% of patients on the pembrolizumab arm experienced all-cause grade 3 to 5 adverse effects (AEs) vs 17.7% in the placebo arm. Additionally, 20.7% of patients in the experimental group experienced AEs leading to treatment discontinuation and 0.4% had AEs leading to death vs 2.0% and 0.2%, respectively, in the placebo arm.

Grade 3 to 5 treatment-related AEs (TRAEs) occurred in 18.9% of those in the pembrolizumab arm vs 1.2% of those in the placebo arm. A total of 17.6% and 0.6% of patients in both respective groups had TRAEs leading to discontinuation, although no patients died due to TRAEs.

The most common low-grade TRAEs in the placebo arm were fatigue (20.3%), pruritus (18.6%) and hypothyroidism (17.6%) compared with fatigue (14.3%), pruritus (11.5%), and diarrhea (10.3%) in the placebo group. Additionally, grade 3/4 TRAEs in the experimental arm included diarrhea, fatigue, and rash.

First-line pembrolizumab currently has several other indications across the United States, Europe, and Japan in combination with axitinib (Inlyta) for patients with advanced RCC. It is also being investigated both as a single agent and in combination with other investigational drugs across a range of settings and stages for RCC, including adjuvant treatments and regimens for advanced or metastatic disease.


  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. August 10, 2021. Accessed August 10, 2021. https://bit.ly/3fLSKFG
  2. 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. 2021;39(suppl 15):LBA5. doi:10.1200/JCO.2021.39.15_suppl.LBA5
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