Trial results for the Phase 3 study investigating coformulated favezelimab/pembrolizumab (MK-4280A) in previously treated metastatic colorectal cancer were posted on ClinicalTrials.gov on 2025-09-17. The study's primary hypothesis, that favezelimab/pembrolizumab would be superior to standard of care in overall survival, was not met, with the experimental arm showing a median overall survival of 7.3 months compared to 8.5 months for standard of care.
Background
The study, titled "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)," aimed to evaluate the safety and efficacy of MK-4280A in participants with previously treated metastatic PD-L1 positive colorectal cancer. Pembrolizumab is an established immunotherapy.
Trial design
The MK-4280A-007 study (NCT05064059) was a Phase 3, randomized trial that enrolled 441 participants with previously treated metastatic PD-L1 positive colorectal cancer. Participants were randomized to receive either coformulated favezelimab/pembrolizumab or standard of care, which included regorafenib or TAS-102 (trifluridine and tipiracil). The primary endpoint of the study was overall survival.
Key results
The trial results showed that the primary endpoint of overall survival was not met.
- For Overall Survival (OS), the median was 7.3 months for the favezelimab/pembrolizumab arm and 8.5 months for the Standard of Care arm. The Hazard Ratio (HR) was 0.98 (95% Confidence Interval: 0.8 to 1.2), with a p-value of 0.4183.
For Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR):
- The median PFS was 2.1 months for the favezelimab/pembrolizumab arm and 2.6 months for the Standard of Care arm. The Hazard Ratio (HR) was 1.34 (95% Confidence Interval: 1.09 to 1.64), with a p-value of 0.9967.
For Objective Response Rate (ORR) per RECIST 1.1 as assessed by BICR:
- The ORR was 6.8% for the favezelimab/pembrolizumab arm and 0.9% for the Standard of Care arm. The difference in percentage was 5.9% (95% Confidence Interval: 2.5 to 10.1), with a p-value of 0.0007.
Regarding safety:
- 205 participants in the favezelimab/pembrolizumab arm experienced at least one adverse event (AE), compared to 199 participants in the Standard of Care arm.
- 21 participants in the favezelimab/pembrolizumab arm discontinued study treatment due to an AE, compared to 19 participants in the Standard of Care arm.
What this means
The Phase 3 MK-4280A-007 study did not demonstrate that coformulated favezelimab/pembrolizumab was superior to standard of care in improving overall survival or progression-free survival in patients with previously treated metastatic PD-L1 positive colorectal cancer. While the experimental arm showed a statistically significant improvement in objective response rate, this did not translate into a benefit in the primary endpoint of overall survival. These results indicate that favezelimab/pembrolizumab did not meet its primary efficacy objective in this patient population.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT05064059, titled "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)," were posted on 2025-09-17 on clinicaltrials.gov.