Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced first-time results from the pivotal Phase 3 KEYNOTE-564 trial evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, for the potential adjuvant treatment of patients with renal cell carcinoma (RCC) at intermediate-high or high risk of recurrence following nephrectomy (surgical removal of a kidney) or following nephrectomy and resection of metastatic lesions. After a median follow-up of 24.1 months (14.9-41.5), KEYTRUDA demonstrated a statistically significant and clinically meaningful reduction in the risk of disease recurrence or death by 32% compared to placebo (HR=0.68 [95% CI, 0.53–0.87]; p=0.0010). Additionally, a favorable trend in overall survival (OS) was observed with a 46% reduction in the risk of death with KEYTRUDA as compared to placebo (HR=0.54 [95% CI, 0.30–0.96]; p=0.0164). As previously announced, the trial will continue to evaluate OS, a key secondary endpoint.

“With the results of KEYNOTE-564, pembrolizumab is the first immunotherapy to show a clinical benefit in the adjuvant setting in kidney cancer,” said Dr. Toni K. Choueiri, director of the Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School. “It took several decades to achieve this milestone. We hope to build on this important research and provide new treatment options to kidney cancer patients.”

“As nearly half of early-stage renal cell carcinoma patients experience disease recurrence after surgery, we are particularly encouraged to see that KEYTRUDA demonstrated a statistically significant reduction in the risk of recurrence or death by 32% compared with placebo in this study,” said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. “These data highlight the opportunity for KEYTRUDA to become a new standard of care for patients with early-stage renal cell carcinoma and we look forward to working closely with regulatory authorities to make this treatment option available to patients.”

The late-breaking results will be presented in the Plenary session of the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #LBA5) on Sunday, June 6, 2021. As announced, data spanning more than 20 types of cancer will be presented from Merck’s oncology research program at ASCO. A compendium of presentations and posters of Merck-led studies will be posted by Merck on Friday, June 4 at 9 a.m. ET. Follow Merck on Twitter via @Merck and keep up to date with ASCO news and updates by using the hashtag #ASCO21.

Merck is continuing to study KEYTRUDA, in combination or as monotherapy, as well as other investigational products across multiple settings and stages of RCC including adjuvant and advanced or metastatic disease through our broad clinical development program, which includes over 20 clinical studies and more than 4,000 patients.

KEYTRUDA is currently approved in the U.S., Europe and Japan in combination with axitinib for the first-line treatment of patients with advanced RCC.

Study Design and Additional Data from KEYNOTE-564

KEYNOTE-564 is a randomized, double-blind, Phase 3 trial (ClinicalTrials.gov, NCT03142334) evaluating KEYTRUDAmonotherapy versus placebo for the adjuvant treatment of patients with RCC who have undergone nephrectomy and who have intermediate-high risk, high risk, or M1 no evidence of disease (M1 NED) RCC with clear cell component. The study enrolled 994 patients who were randomized to receive either KEYTRUDA (200 mg intravenously [IV] on Day 1 of each three-week cycle for up to 17 cycles) or placebo (saline solution IV on Day 1 of each three-week cycle for up to 17 cycles). The primary endpoint is disease-free survival (DFS), and the secondary endpoints include OS and safety.

As of data cutoff (Dec. 14, 2020), the median study follow-up was 24.1 months. Findings showed KEYTRUDA demonstrated a statistically significant improvement in DFS in patients with RCCfollowing nephrectomy or following nephrectomy and resection of metastatic lesions compared with placebo (HR=0.68 [95% CI, 0.53–0.87]; p=0.0010). Additionally, the two-year estimated DFS rate was 77.3% with KEYTRUDA versus 68.1% with placebo. Overall, the DFS benefit was consistent across subgroups. Median DFS was not achieved in either treatment arm based on event accrual.

Grade 3-5 treatment-related adverse events (TRAEs) occurred in 18.9% of patients in the KEYTRUDA arm and 1.2% of patients in the placebo arm. TRAEs resulting in discontinuation of any treatment occurred in 17.6% of patients in the KEYTRUDA arm and 0.6% of patients in the placebo arm. The most common TRAEs of any grade (occurring in ≥5% of patients) were fatigue (20.3%), pruritus (18.6%) and hypothyroidism (17.6%) in the KEYTRUDA arm and fatigue (14.3%), pruritus (11.5%) and diarrhea (10.3%) in the placebo arm. The most common immune-mediated adverse events of any grade (occurring in ≥3% of patients) were hypothyroidism (21.1%) and hyperthyroidism (11.9%) in the KEYTRUDA arm and hypothyroidism (3.6%) in the placebo arm. No treatment-related deaths occurred.