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.

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LBA248 Background: Effective treatment options remain an unmet need for patients (pts) with microsatellite stable/mismatch repair proficient (MSS/pMMR) metastatic colorectal cancer (mCRC). Combination therapy with the anti–lymphocyte activation gene (LAG)-3 antibody favezelimab (fave) and the PD-1 inhibitor pembrolizumab (pembro), has shown promising antitumor activity and manageable safety in PD-L1 CPS ≥1 MSS/pMMR mCRC. The phase 3 KEYFORM-007 study (NCT05064059) evaluated the efficacy and safety of co-formulated fave/pembro vs standard-of-care (SOC) in PD-L1–positive MSS/pMMR mCRC. We present results of the pre-specified final analysis of OS. Methods: Eligible pts with PD-L1 CPS ≥1, MSS/pMMR unresectable mCRC (Stage IV per AJCC 8 th edition), who had progressed on or after, or could not tolerate standard treatment were randomized 1:1 to co-formulated fave 800 mg/pembro 200 mg IV Q3W (Arm A) or SOC (regorafenib 160 mg PO Q4W [QD on days 1-21] or TAS-102 35 mg/m 2 PO Q4W [BID on days 1-5 and 8-12]) (Arm B). Randomization was stratified by geographic region, presence or absence of liver metastases, and time from initial diagnosis of metastatic disease to randomization. Treatment continued for up to 35 cycles or until unacceptable toxicity, progression, confirmed CR (Arm A), or withdrawal. The primary endpoint was OS. The data cut-off was August 15, 2024. Secondary endpoints included PFS, ORR, and DOR (central review, RECIST v1.1 [assessed at interim analysis with data cut-off of August 21, 2023]), and safety. Results: At final analysis, 441 pts (63% male; 59% RAS mutant) were randomized (221 fave/pembro; 220 SOC. Median follow-up was 28 mo (range, 21-32). Median OS was not superior with fave/pembro vs SOC (median 7.3 vs 8.5 mo; HR 0.98; 95% CI, 0.80-1.20; P = 0.4183) in pts with MSS/pMMR mCRC. PFS was not superior with fave/pembro vs SOC (median 2.1 vs 2.6 mo; HR 1.34; 95% CI, 1.09-1.64; nominal P = 0.997). Per protocol, PFS was not tested for statistical significance. A confirmed objective response occurred in 15 (14PR; 1CR [6.8%]) vs 2 (2PR; [0.9%]) pts in the fave/pembro and SOC arms, with best response of PD occurring in 143 (65%) vs 94 (43%) pts, respectively. Median DOR was not reached ([NR] range, 1.8 to 16.8+) among the 15 responders in the fave/pembro arm, and was 6.5+ mo and 12.4 mo, for the 2 responders in the SOC arm. At final analysis, treatment-related adverse events (TRAEs) occurred in 145 (66%) vs 167 (80%) pts, respectively (grade ≥3 in 44 [20%] vs 76 [36%] pts). Adverse events of special interest occurred in 84 (38%) vs 13 (6%) pts, respectively. Conclusion: At final analysis, co-formulated fave/pembro did not improve OS vs SOC in pts with PD-L1-positive MSS/pMMR mCRC. The safety profile was manageable with no new safety signals observed. Clinical trial information: NCT05064059 .