Multinational randomized phase 1b-2 trial of first-line tiragolumab plus atezolizumab and chemotherapy for locally advanced or metastatic esophageal cancer

Chemotherapy with or without immunotherapy is a standard of care first-line treatment for locally advanced or metastatic esophageal cancer (LA/M EC). However, outcomes remain poor. The phase 1b-2 MORPHEUS-EC trial, at 20 centers in six countries, evaluated addition of tiragolumab (anti-TIGIT) to first-line atezolizumab (anti-PD-L1) and cisplatin-fluorouracil chemotherapy for LA/M EC. The study included 152 patients, who were assigned to tiragolumab plus atezolizumab and chemotherapy (n=63), atezolizumab and chemotherapy (n=65), or chemotherapy alone (n=24). Median follow-up for the three groups was 10.9 months, 11.4 months, and 8.7 months, respectively. Investigator-assessed confirmed objective response rate (primary endpoint) was 67.7% (95% CI 54.7-79.1) in the tiragolumab plus atezolizumab plus chemotherapy group, 53.8% (41.0-66.3) in the atezolizumab plus chemotherapy group, and 47.8% (26.8-69.4) in the chemotherapy alone group. Grade 3 or 4 adverse events in the three groups were reported for 79%, 80%, and 74%, respectively, and serious adverse events for 58%, 51%, and 48%, respectively. No deaths were treatment-related. The authors conclude that these results support the additional benefit of tiragolumab combined with atezolizumab and chemotherapy for patients with treatment-naïve, LA/M EC.