Background: In the dose-confirmation phase of this multicohort trial (NCT02720068), the anti-LAG-3 antibody favezelimab had a manageable safety profile and promising antitumor activity in patients (pts) with advanced solid tumors, confirming preliminary RP2D. Here we present results on the safety of favezelimab (fave) plus pembrolizumab (pembro) in all treated pts and efficacy in pts with advanced gastric cancer. Methods: In this phase 1b trial eligible pts aged ≥ 18 years were enrolled into 7 cohorts across 3 tumor types: Cohorts A (3L+ CRC), B (1L/2L CRC), C (PD-1 naïve HNSCC), D (PD-1 refractory HNSCC), E (PD-1 naïve gastric cancer), F (all solid tumors), and G (PD-1 naïve 3L CRC). Pts with gastric cancer in cohort E received either 200 mg fave + 200 mg pembro, or 700 mg fave + 200 mg pembro Q3W up to 35 cycles. Treatment continued until progression, unacceptable toxicity, or pt withdrawal. Primary endpoint was safety and tolerability of fave + pembro. Secondary endpoint was ORR per RECIST 1.1 by investigator assessment. Exploratory endpoints were PFS per RECIST 1.1, and OS. Data cutoff date was March 21, 2022. Results: At data cutoff, 397 pts were enrolled: 38 to fave, 368 to fave + pembro including 9 who crossed over from fave alone. Of these, 80 pts had gastric cancer; 50 (62.5%) of which had ≥2 lines of treatment, and 48 (60.0%) had PD-L1 CPS≥ 1. Among 368 pts treated with fave + pembro, treatment-related adverse events (TRAEs) occurred in 232 (63.0%) with fave + pembro. Grade ≥3 TRAEs occurred in 66 (17.9%) pts with fave + pembro. There were no grade 5 TRAEs. Immune-mediated adverse events (AEs) occurred in 121 (32.9%) pts with fave + pembro. Grade ≥3 immune-mediated AEs occurred in 27 (7.3%) pts with fave + pembro. No grade 5 immune-mediated AEs occurred. In pts with gastric cancer, the overall ORR was 11.3% (95% CI, 5.3-20.3 [3.8% CR; 7.5% PR]) with fave + pembro. In 2 arms, higher dose of fave (700mg) showed increased ORR and 12 months PFS rate. The table summarizes antitumor activity in the gastric cancer cohort. Conclusions: Favezelimab alone or in combination with pembrolizumab had an acceptable safety profile. The combination therapy showed antitumor activity in line with other checkpoint inhibitors in advanced gastric cancer though higher antitumor activity was seen in PDL1 CPS≥ 1 tumors, particularly at higher dose. Clinical trial information: NCT02720068.

^aPts with missing PD-L1 status: 7 pts with 200 mg fave + 200 mg pembro, and 5 with 700 mg fave + 200 mg pembro.