Favezelimab/Pembrolizumab Coformulation Versus Standard-of-Care in PD-L1–Positive Metastatic Colorectal Cancer: The Phase III, Randomized KEYFORM-007 Study
Abstract
The phase III KEYFORM-007 study (ClinicalTrials.gov identifier: NCT05064059 ) evaluated the efficacy and safety of coformulated favezelimab/pembrolizumab versus standard-of-care (SOC) in PD-L1–positive microsatellite stable/mismatch repair proficient (MSS/pMMR) metastatic colorectal cancer (mCRC). We present results of the final analysis of overall survival (OS). Eligible participants with PD-L1 combined positive score ≥1, MSS/pMMR unresectable mCRC who had progressed on or could not tolerate standard treatment were randomly assigned 1:1 to coformulated favezelimab 800 mg/pembrolizumab 200 mg intravenously once every 3 weeks or SOC (regorafenib 160 mg orally once every 4 weeks [once daily on days 1-21] or TAS-102 35 mg/m 2 orally once every 4 weeks [twice a day on days 1-5 and 8-12]). The primary end point was OS. Secondary end points included progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and safety. At final analysis, 441 participants were randomly assigned (221 favezelimab/pembrolizumab; 220 SOC). Median follow-up was 28 months (range, 21-32). OS was not superior with favezelimab/pembrolizumab versus SOC (median 7.3 v 8.5 months; hazard ratio [HR], 0.98 [95% CI, 0.80 to 1.20]; P = .4183) in participants with MSS/pMMR mCRC. PFS was not superior with favezelimab/pembrolizumab versus SOC (median 2.1 v 2.6 months; HR, 1.34 [95% CI, 1.09 to 1.64]; nominal P = .997). The ORR was 6.8% (14 partial response [PR]; one complete response) versus 0.9% (two PR) with favezelimab/pembrolizumab versus SOC. Median DOR was not reached (range, 1.8 to 16.8+) among the 15 responders in the favezelimab/pembrolizumab arm and was 6.5+ months and 12.4 months for the two responders in the SOC arm. Grade ≥3 treatment-related adverse events occurred in 44 (20%) and 76 (36%) participants, respectively. At final analysis, coformulated favezelimab/pembrolizumab did not improve OS versus SOC in patients with PD-L1–positive MSS/pMMR mCRC. The safety profile was manageable with no new safety signals observed. This coformulation is not recommended for use in this patient population.