Merck Updates on Phase 3 KEYFORM-007 Trial of Favezelimab and Pembrolizumab for Treated PD-L1 Positive Metastatic Colorectal Cancer

RAHWAY, NJ, USA I September 25, 2024 I Merck (NYSE: MRK), known as MSD outside of the United States and Canada, has announced that their Phase 3 KEYFORM-007 trial did not meet its primary endpoint of overall survival (OS) for patients with previously treated PD-L1 positive microsatellite stable (MSS) metastatic colorectal cancer (mCRC). This trial evaluated the investigational fixed-dose combination of favezelimab, Merck’s anti-LAG-3 antibody, and pembrolizumab (KEYTRUDA®), Merck’s anti-PD-1 therapy. The fixed-dose combination did not show an improvement in OS when compared to the standard treatments, regorafenib or TAS-102 (trifluridine and tipiracil hydrochloride).

The safety profile for the combination was consistent with what has been observed in earlier studies for favezelimab and pembrolizumab, with no new safety signals identified. Merck plans to conduct a full evaluation of the data and collaborate with investigators to present the findings to the scientific community.

Dr. M. Catherine Pietanza, Vice President of Global Clinical Development at Merck Research Laboratories, commented on the difficulty in treating metastatic colorectal cancer, especially for patients with microsatellite stable disease, which typically shows limited response to immunotherapies. She expressed gratitude to the patients and investigators for their participation and affirmed Merck's commitment to continuing the clinical development program to explore KEYTRUDA-based combinations and other novel candidates for colorectal cancer treatment.

In the United States, KEYTRUDA is currently approved for treating patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer as determined by an FDA-approved test. However, it is not approved for treating MSS mCRC.

The favezelimab and pembrolizumab combination is also under examination for other types of cancers, including certain hematologic malignancies and multiple solid tumors. Another ongoing study, KEYFORM-008, is a Phase 3 investigation into the combination's efficacy in patients with relapsed or refractory classical Hodgkin lymphoma whose disease has advanced despite prior anti-PD-1 therapy.

KEYFORM-007 is a randomized, open-label Phase 3 trial (ClinicalTrials.gov, NCT05064059) that compares the fixed-dose combination of favezelimab and pembrolizumab (MK-4280A) to standard care treatments, such as regorafenib or TAS-102, in patients with PD-L1 positive MSS mCRC who have previously undergone standard therapies. The trial's primary endpoint is overall survival, with secondary endpoints including progression-free survival, objective response rate, duration of response, safety, and quality of life. The trial involved 441 patients who were randomized to receive either the combination treatment or one of the standard care options.

Colorectal cancer, also referred to as colon or rectal cancer based on its origin, often begins as polyps on the inner lining of the colon or rectum. It is the third most commonly diagnosed cancer and the second leading cause of cancer-related death globally. Approximately 1.9 million new cases and over 900,000 deaths were reported worldwide in 2022. In the United States, around 107,000 new cases of colon cancer and 46,000 new cases of rectal cancer are expected in 2024, with over 53,000 deaths from colorectal cancer projected. The five-year relative survival rates in the U.S. for metastatic colon and rectal cancer are estimated at 13% and 18%, respectively.

Favezelimab (MK-4280) is an investigational anti-LAG-3 antibody designed to restore T cell effector function by preventing LAG-3 from binding to its primary ligand, MHC class II molecules. The fixed-dose combination of favezelimab and pembrolizumab (MK-4280A) is being tested across multiple solid tumor types and in patients with relapsed or refractory classical Hodgkin lymphoma whose disease has not responded to previous anti-PD-1 therapy.

KEYTRUDA (pembrolizumab) is an anti-PD-1 therapy that enhances the immune system's ability to detect and fight tumor cells. It blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thus activating T lymphocytes, which can attack both tumor and healthy cells. Merck's clinical research program for KEYTRUDA is among the largest in the industry, with over 1,600 trials exploring its efficacy across various cancers and treatment settings.