A Phase 3 study evaluating coformulated favezelimab/pembrolizumab (MK-4280A) for previously treated metastatic colorectal cancer reached its primary completion on 2024-08-15. The trial found that the experimental coformulation did not demonstrate superiority in overall survival, with a median of 7.3 months compared to 8.5 months for standard of care.
Background
This study investigated pembrolizumab, coformulated with favezelimab as MK-4280A, in participants with previously treated metastatic PD-L1 positive colorectal cancer. The primary objective was to assess the safety and efficacy of MK-4280A, specifically comparing it against standard of care treatments, which included regorafenib and TAS-102 (trifluridine and tipiracil). The central hypothesis of the study was that MK-4280A would be superior to standard of care with respect to overall survival.
Trial design
The Phase 3 study (NCT05064059) enrolled 441 participants with colorectal cancer. The trial compared the coformulated intervention of favezelimab/pembrolizumab against a standard of care arm, which consisted of either regorafenib or TAS-102. The primary study hypothesis focused on demonstrating superiority of the coformulated treatment over standard of care in terms of overall survival.
Key results
The trial reported the following key outcome measurements:
- Overall Survival (OS): The median OS for the favezelimab/pembrolizumab group was 7.3 Months, while the standard of care group achieved a median OS of 8.5 Months. The hazard ratio was 0.98 (95% Confidence Interval: 0.8 to 1.2), with a p-value of 0.4183, indicating no statistically significant difference in overall survival.
- Progression-Free Survival (PFS): Median PFS was 2.1 Months for the favezelimab/pembrolizumab group and 2.6 Months for the standard of care group. The hazard ratio was 1.34 (95% Confidence Interval: 1.09 to 1.64), with a p-value of 0.9967, also showing no statistically significant difference.
- Objective Response Rate (ORR): The ORR for the favezelimab/pembrolizumab group was 6.8 Percentage of Participants, compared to 0.9 Percentage of Participants in the standard of care group. The difference in percentage was 5.9 (95% Confidence Interval: 2.5 to 10.1), with a p-value of 0.0007, suggesting a statistically significant improvement in ORR for the coformulated treatment.
Regarding safety, 205 participants in the favezelimab/pembrolizumab group experienced at least one adverse event, with 21 participants discontinuing treatment due to an adverse event. In the standard of care group, 199 participants experienced at least one adverse event, and 19 participants discontinued treatment due to an adverse event.
What this means
The results of this Phase 3 study indicate that coformulated favezelimab/pembrolizumab did not meet its primary endpoint of improving overall survival in previously treated metastatic colorectal cancer, nor did it show an improvement in progression-free survival compared to standard of care. However, the experimental treatment did demonstrate a statistically significant improvement in objective response rate. While the primary efficacy endpoints were not met, the observed improvement in ORR might warrant further investigation into specific patient subgroups or alternative endpoints. The safety profile, in terms of the number of participants experiencing adverse events and discontinuing treatment due to them, appears broadly similar between the two treatment arms.
Source
The information regarding this trial's primary completion and results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for the 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 2024-08-15 on clinicaltrials.gov.