Pembrolizumab/Favezelimab Combo Fails to Extend Survival in Advanced mCRC

Microscopic, photorealistic image of colorectal cancer cells - Generated with Adobe Firefly

The phase 3 KEYFORM-007 study (NCT05064059) evaluating the anti–LAG-3 antibody favezelimab in combination with the anti–PD-1 therapy pembrolizumab (Keytruda) in patients with previously treated PD–L1-positive microsatellite stable (MSS) metastatic colorectal cancer (mCRC) did not meet its primary end point of overall survival (OS).¹

“Metastatic colorectal cancer continues to be a challenging disease to treat, especially for the majority of patients who have microsatellite stable disease, which has had limited response to immunotherapies,” said M. Catherine Pietanza, MD, vice president, global clinical development, Merck Research Laboratories, in a press release. “We are grateful to the patients and investigators for their participation in this study, and we will continue to advance our clinical development program to evaluate [pembrolizumab]-based combinations and novel candidates for patients with colorectal cancer in need of new options.”

A full analysis of the data is ongoing and will be shared with the scientific community.

In June 2020, the FDA approved pembrolizumab for the first-line treatment of microsatellite instability-high or mismatch repair deficient CRC.²

The fixed-dose combination of favezelimab and pembrolizumab is also being investigated in the KEYFORM-008 study (NCT05508867) for the treatment of patients with PD–(L)1-refractory classical Hodgkin lymphoma.¹

About KEYFORM-007

The randomized, open-label, phase 3 KEYFORM-007 study enrolled 441 patients with PD–L1-positive, MSS, mCRC who previously received standard therapy. Patients were randomized 1:1 to receive the fixed-dose combination of 800 mg favezelimab and 200 mg pembrolizumab on day 1 of a 3-week cycle for 35 cycles or investigator’s choice of regorafenib (Stivarga) or trifluridine/tipiracil (Lonsurf; TAS-102).

Along with the primary end point of OS, secondary end points included progression-free survival, objective response rate, duration of response, incidence of adverse events, discontinuation due to adverse events, and change from baseline in quality of life.³

Patients were eligible for enrollment in the study if they had an ECOG performance status of 0 or 1, a life expectancy of at least 3 months, and adequate organ function. Those with active central nervous system metastases, clinically significant cardiovascular disease, a known additional malignancy, active autoimmune disease, or a history of HIV infection were not eligible for study participation.

REFERENCES:

1. Merck provides update on phase 3 KEYFORM-007 trial evaluating investigational fixed-dose combination of favezelimab and pembrolizumab for patients with previously treated PD-L1 positive microsatellite stable metastatic colorectal cancer. News release. Merck. September 25, 2024. Accessed September 25, 2024. https://tinyurl.com/7hw84z2c

2. FDA approves pembrolizumab for first-line treatment of MSI-H/dMMR colorectal cancer. News release. FDA. June 29, 2020. Accessed September 25, 2024. https://tinyurl.com/muzvnxhb

3. A study of coformulated favezelimab/​pembrolizumab (MK-4280A) versus standard of care in subjects with previously treated metastatic PD-L1 positive colorectal cancer (MK-4280A-007). ClinicalTrials.gov. Updated August 23, 2024. Accessed September 25, 2024. https://clinicaltrials.gov/study/NCT05064059