Gilead Sciences, Inc. and Arcus Biosciences, Inc. announced that domvanalimab plus zimberelimab and chemotherapy showed encouraging overall response rate (ORR) and six-month progression-free survival (PFS) rate results in a preliminary analysis from Arm A1 of the EDGE-Gastric study. This ongoing Phase 2, multi-arm, global study is evaluating the safety and efficacy of various combinations of the Fc-silent anti-TIGIT antibody domvanalimab plus the anti-PD-1 antibody zimberelimab and chemotherapy in patients with locally advanced unresectable or metastatic gastric, gastroesophageal junction or esophageal adenocarcinoma. These results will be presented during the American Society of Clinical Oncology (ASCO) Monthly Plenary Series, a virtual forum for presentation and discussion of the latest cancer research.

These early data are encouraging and indicate the potential for the anti-TIGIT, domvanalimab-based therapy to improve upon anti-PD-1 and chemotherapy in this setting, with a similar safety profile to anti-PD-1 and chemotherapy. At data cutoff (September 4, 2023), 41 patients were enrolled and treated with a median follow-up of 8.1 months; 24 patients (59%) remained on study treatment at time of data cutoff. Median time on treatment was 33 weeks (range: <1 to 53 weeks).

The domvanalimab-containing regimen showed an objective response rate (ORR) of 80% in patients with PD-L1-high tumors (tumor activity positivity (TAP) >=5%), 46% in patients with PD-L1-low tumors (TAP <5%) and 59% for patients overall. There were two confirmed complete responses. Six-month landmark PFS rate was 93% for patients with PD-L1-high tumors (TAP >=5%), 68% for patients with PD-L1-low tumors (TAP <5%) and 77% for patients overall.

Median PFS was not reached and mature PFS data are expected in the second half of next year. umor samamples from 2 patients were not available for central PD-L1 testing CI: confidence interval The domvanalimab-containing regimen was well tolerated, with a similar safety profile to what has been reported for anti-PD-1 plus chemotherapy in this setting. The most common adverse events (AEs) were neutropenia (59%), nausea (54%), anemia (27%) and fatigue (27%).

Infusion-related reactions were observed in 20% and the majority (17%) were related to chemotherapy. No patients experienced serious immune-mediated AEs, and there were no treatment-emergent adverse events (TEAEs) resulting in death. These data add to the growing body of evidence that domvanalimab, an Fc-silent anti-TIGIT antibody, has a differentiated safety and tolerability profile relative to published data from studies with Fc-enabled anti-TIGIT antibodies.

The preliminary data from Arm A1 of the Phase 2 EDGE-Gastric study support the ongoing Phase 3 study, STAR-221, in unresectable or metastatic upper GI cancers. The companies have three additional ongoing Phase 3 registrational studies of domvanalimab-containing regimens in lung cancer, including STAR-121, ARC-10 and PACIFIC-8. Domvanalimab and zimberelimab are investigational molecules. Neither Gilead nor Arcus has received approval from any regulatory authority for any use globally, and their safety and efficacy for the treatment of gastrointestinal and lung cancers have not been established.