Phase III KEYFORM-007 Trial Fails to Show Survival Benefit for Favezelimab Plus Pembrolizumab in Microsatellite Stable Colorectal Cancer
The phase III KEYFORM-007 clinical trial demonstrated that coformulated favezelimab combined with pembrolizumab failed to improve overall survival compared with standard therapy in patients with PD-L1-positive, microsatellite stable and mismatch repair-proficient metastatic colorectal cancer. The findings highlight the ongoing difficulty of extending immunotherapy benefits beyond the roughly 5% of colorectal cancer patients who possess microsatellite instability-high (MSI-H/dMMR) tumors.
Trial Design and Patient Characteristics in KEYFORM-007
KEYFORM-007 operated as a randomized, open-label, active-controlled phase III study that enrolled 441 patients across 117 centers in 20 countries. Eligible participants had unresectable or metastatic colorectal adenocarcinoma, centrally confirmed pMMR disease, and a PD-L1 combined positive score of 1 or higher. Investigators randomized patients in a 1:1 ratio to receive either intravenous favezelimab at 800 mg plus pembrolizumab at 200 mg every three weeks for up to 35 cycles, or an investigator-selected standard of care consisting of regorafenib or trifluridine-tipiracil (TAS-102).
The study population consisted of heavily pretreated patients with a median age of 59 years. Among the enrolled cohort, 70 percent of patients presented with left-sided tumors, 59 percent carried RAS-mutant disease, and 78 percent had liver metastases at baseline. Researchers stratified randomization by geographic region, presence of liver metastases, and the time elapsed since diagnosis of metastatic disease.
Survival Endpoints and Dual Checkpoint Blockade Outcomes
At the prespecified final analysis after a median follow-up of approximately 28 months, 395 patient deaths had occurred. The median overall survival reached 7.3 months for patients receiving favezelimab and pembrolizumab, compared with 8.5 months for those receiving the standard of care, yielding a hazard ratio of 0.98. Progression-free survival similarly favored the control arm, with a median of 2.1 months for the immunotherapy combination versus 2.6 months for standard therapy.
Despite the negative primary survival endpoint, the objective response rate reached 6.8 percent in the experimental arm compared with 0.9 percent in the control arm. Fifteen patients in the immunotherapy group achieved an objective response, featuring one complete response and 14 partial responses, whereas the control arm produced only two partial responses. Progressive disease served as the best overall response for 65 percent of patients in the favezelimab-pembrolizumab group, compared with 43 percent in the standard therapy group.
Subgroup Analysis Examining the Impact of Liver Metastases
An exploratory evaluation assessed outcomes based on baseline liver involvement, given that 78 percent of trial participants harbored hepatic metastases. Among the subgroup without liver metastases, median overall survival reached 14.4 months for the immunotherapy combination versus 12.9 months for the standard of care, with 18-month overall survival rates recorded at 37 percent and 28 percent, respectively. The objective response rate in this specific subset reached 12.2 percent for the experimental arm compared with 2 percent for the control arm.
Median progression-free survival in patients without liver metastases did not favor the experimental treatment, registering at 2.4 months for the immunotherapy combination versus 4.4 months for standard therapy. Investigators noted that these subgroup findings remain strictly hypothesis-generating, as the ad hoc analysis lacked statistical power to definitively establish differential efficacy according to metastatic site.
Frequently Asked Questions About the KEYFORM-007 Trial
What specific drugs were evaluated in the KEYFORM-007 study?
The trial evaluated coformulated favezelimab, an investigational lymphocyte-activation gene 3 (LAG-3) inhibitor, combined with pembrolizumab, a PD-1 inhibitor. This experimental immunotherapy combination was tested against investigator-selected standard of care treatments, which included regorafenib or trifluridine-tipiracil (TAS-102).
How many patients participated in the trial and across how many global sites?
A total of 441 patients were enrolled in the trial. These participants were treated across 117 medical centers located in 20 different countries.
What was the primary endpoint of the KEYFORM-007 study?
The primary endpoint of the phase III trial was overall survival. Secondary endpoints included progression-free survival, objective response rate, duration of response, health-related quality of life, and safety.
Did any patients achieve a complete response from the immunotherapy combination?
Yes. Fifteen patients in the favezelimab plus pembrolizumab arm achieved an objective response, which included one complete response and 14 partial responses. By comparison, the control arm produced two partial responses.
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