Background: Dual blockade of immune checkpoint molecules, PD-1 and LAG-3, has been proposed to restore T-cell function and thus enhance antitumor responses. This Phase I trial evaluated BI 754091 (anti-PD-1) with BI 754111 (anti-LAG-3) antibodies in Asian pts with advanced solid tumors (NCT03433898). Here, we present results from pts with anti-PD-(L)1 inhibitor-naïve gastric/gastroesophageal junction or esophageal cancer (Cohorts A and B). Methods: In Parts 1 and 2 (dose escalation), the recommended dose for the combination was determined as BI 754091 240 mg + BI 754111 600 mg IV Q3W. In Part 3, the combination was assessed in expansion cohorts including pts with gastric/gastroesophageal junction cancer (Cohort A) and esophageal cancer (Cohort B). Eligible pts had received ≥1 line of prior systemic therapy but no prior anti-PD-(L)1 therapy. The primary endpoint in Part 3 was objective response (OR; confirmed complete response or partial response [PR]) per RECIST 1.1. Results: In Cohort A/B, 36/37 pts were treated:26/31 (72/84%) male, median age 60/63 years. Patients were enrolled in Taiwan (1/7 pts, 3/19%), Japan (12/27 pts, 33/73%) or Korea (23/3 pts, 64/8%). The median number of regimens of prior systemic therapy was 2/2 (Cohorts A/B, range: 1?6/1?4). All pts in Cohort B had squamous cell carcinoma. At the time of analysis, pts in Cohort A/B had undergone a median of 84/73 days on treatment (range: 31?346/8?325), from the start of treatment until the date of snapshot, death or discontinuation. Confirmed OR (PR) was observed in 4/7 pts in Cohorts A/B; overall response rate (ORR) was 11% and 19%. Stable disease (SD) was observed in 10/8 (28/22%) pts in Cohorts A/B and overall disease control rate was 39/41%. In Cohorts A/B, adverse events (AEs) and treatment-related AEs were experienced by 30/34 (83/92%) and 12/22 (33/59%) pts, respectively. The most commonly reported AEs were pyrexia (25/19%), decreased appetite (17/19%), increased aspartate aminotransferase (11/14%), anemia (11/11%) and nausea (6/14%). In Cohort A/B, 9/15 (25/41%) pts experienced immune-related AEs, most commonly rash in Cohort A (4 pts; 11%) and hyperthyroidism in Cohort B (4 pts; 11%). In Cohorts A/B, 2/6 (6/16%) patients experienced AEs leading to discontinuation of treatment. Conclusions: Treatment was well tolerated and preliminary antitumor activity was seen. Addition of LAG3 did not improve ORR beyond that expected for an anti-PD-1 monotherapy in gastric and esophageal cancer without patient selection. Clinical trial information: NCT03433898

*Grade 4 AEs include one patient with liver disorder (not drug-related), and one patient with pneumonia (drug-related) and hypotension (not drug-related). ^?Grade 5 AE was acute kidney injury (not drug-related).