Merck announced that the US Food and Drug Administration (FDA) has approved KEYTRUDA (pembrolizumab) and KEYTRUDA QLEX (pembrolizumab and berahyaluronidase alfa-pmph), Merck’s anti-PD-1 therapies, each in combination with WELIREG (belzutifan), Merck’s first-in-class, oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, for the adjuvant treatment of adult patients with Renal Cell Carcinoma (ccRCC) with a clear cell component at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. These approvals represent the first approval for WELIREG in earlier-stage ccRCC and the first approvals for PD-1 and HIF-2α inhibitor combination regimens.

The approvals are based on results from the pivotal phase 3 LITESPARK-022 trial. LITESPARK-022 enrolled 1,841 patients and demonstrated that KEYTRUDA, in combination with WELIREG, significantly improved Disease-Free Survival (DFS), the trial’s primary endpoint, reducing the risk of disease recurrence, metastasis or death by 28 percent (HR=0.72 [95 percent percent CI 0.59-0.87]; p=0.0003) for patients with ccRCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions compared to KEYTRUDA plus placebo.

Dr. Toni K Choueiri, Director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute and Jerome and Nancy Kohlberg, Professor of Medicine, Harvard Medical School, said, “Patients with earlier-stage Renal Cell Carcinoma at high risk of recurrence after surgery may see their cancer return, frequently as metastatic disease. The results of the LITESPARK-022 trial demonstrated the ability of pembrolizumab in combination with belzutifan to reduce the risk of disease recurrence, metastasis, or death by 28 percent, which represents an important new option for these patients to help keep their clear cell Renal Cell Carcinoma from coming back.”

The estimated 24-month DFS rate was 81 percent (95 percent CI 0.78-0.83) with KEYTRUDA plus WELIREG compared to 74 percent (95 percent CI 0.71-0.77) with KEYTRUDA plus placebo. Median DFS was not reached in either arm. Overall Survival (OS) results were not yet mature at this interim analysis. The effectiveness of KEYTRUDA QLEX for its approved indications has been established based upon evidence from the adequate and well-controlled studies conducted with KEYTRUDA and additional data from MK-3475A-D77 comparing the pharmacokinetic, efficacy, and safety profiles of KEYTRUDA QLEX and KEYTRUDA.

Dr. M. Catherine Pietanza, Vice President, Global Clinical Development, Merck Research Laboratories, said, “Reflecting on my own experience as a clinical oncologist, I know the significant impact that improved disease-free survival can have on the lives of patients. These approvals demonstrate Merck’s commitment to pursuing innovative treatment options that may help these patients experience longer periods without disease.”