Co-Formulated Favezelimab And Pembrolizumab Fails to Improve Survival for Metastatic Colorectal Cancer
According to results from the phase 3 KEYFORM-007 trial, co-formulated favezelimab plus pembrolizumab failed to significantly improve survival compared to standard of care among patients with PD-L1-positive microsatellite stable (MSS) or mismatch repair proficient (pMMR) metastatic colorectal cancer.
These results were presented by Neil Howard Segal, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, New York, at the 2025 ASCO Gastrointestinal Cancers Symposium in San Francisco, California.
While “effective treatment options remain an unmet need for [patients] with microsatellite stable/mismatch repair proficient metastatic colorectal cancer,” Dr Segal et al wrote, “combination therapy with…favezelimab and…pembrolizumab has shown promising antitumor activity and manageable safety” among those patients with MSS/pMMR metastatic colorectal cancer and a PD-L1 combined positive score of ≥1.
In this study, 441 patients in this patient population who could not tolerate or experienced disease progression on or after standard treatment were randomized on a 1-to-1 basis to receive either 800 mg of favezelimab plus 200 mg of pembrolizumab once every 3 weeks (n = 221) or standard regorafenib or TAS-102 (n = 220) for up to 35 cycles, or until disease progression or unacceptable toxicity. Stratification was based on geographic region, presence of liver metastases, and time from initial diagnosis of metastatic disease to randomization. The primary end point was overall survival (OS). Key secondary end points included progression-free survival (PFS), objective response, duration of response, and safety.
At a median follow-up of 28 months, the median OS was 7.3 months in the favezelimab plus pembrolizumab arm and 8.5 months in the standard of care arm (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.80 to 1.20; P = .4183). The median PFS was 2.1 months and 2.6 months, respectively (HR, 1.34; 95% CI, 1.09 to 1.64; P = .997). A confirmed objective response was observed in 15 patients in the favezelimab plus pembrolizumab arm and 2 patients in the standard of care arm. Best response of progressive disease occurred in 65% of patients and 43% of patients, respectively. Median duration of response was not reached among the responders in the favezelimab plus pembrolizumab arm and was >6.5 months and 12.4 months for the 2 responders in the standard of care arm.
Grade ≥3 treatment-related adverse events occurred in 20% of patients in the favezelimab plus pembrolizumab arm and 36% of patients in the standard of care arm. Adverse events of special interest occurred in 38% and 6% of patients, respectively.
As Dr Segal et al concluded, these final analysis results demonstrated that “co-formulated favezelimab/pembrolizumab did not improve median OS vs [standard of care] in [patients] with PD-L1-positive MSS/pMMR mCRC… however the safety profile was manageable with no new safety signals observed.”
Source:
Segal NH, Passhak M, Kose F, et al. Co-formulated favezelimab plus pembrolizumab versus standard-of-care in previously treated, PD-L1-positive metastatic colorectal cancer: The phase 3, randomized KEYFORM-007 study. Presented at 2025 ASCO Gastrointestinal Cancers Symposium. January 23-25, 2025. Abstract LBA248
