Gilead and Arcus announce new data showing encouraging clinical activity of anti-TIGIT domvanalimab-containing regimen as first-line treatment for upper GI cancers

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.

The ongoing, multi-arm, global EDGE-Gastric trial (NCT05329766) is evaluating the safety and efficacy of various combinations of the Fc-silent anti-TIGIT antibody domvanalimab and the anti-PD-1 antibody zimberelimab in patients who have locally advanced unresectable or metastatic gastric, gastroesophageal junction or esophageal adenocarcinoma. Patients in Arm A1, with previously untreated G/GEJ/E adenocarcinoma, received 1600 mg of domvanalimab intravenously (IV) every four weeks (Q4w) plus 480 mg of zimberelimab IV Q4W + FOLFOX (oxaliplatin 85 mg/m2 IV, leucovorin 400 mg/m2 IV, fluorouracil 400 mg/m2 IV bolus + 2400 mg/m2 continuous 46-48-hour IV infusion) every two weeks.

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 ORR of 80% in patients with PD-L1-high tumors (tumor activity positivity (TAP) (greater than or equal to 5%), 46% in patients with PD-L1-low tumors (TAP less than 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 greater than or equal to 5%), 68% for patients with PD-L1-low tumors (TAP less than 5%) and 77% for patients overall. Median PFS was not reached and mature PFS data are expected in the second half of next year.

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 this study support the ongoing Phase III study, STAR-221, in unresectable or metastatic upper GI cancers. The companies have three additional ongoing Phase III registrational studies of domvanalimab-containing regimens in lung cancer, including STAR-121, ARC-10 and PACIFIC-8.

About the EDGE-Gastric Study: The ongoing, multi-arm, global EDGE-Gastric trial (NCT05329766) is evaluating the safety and efficacy of various combinations of the Fc-silent anti-TIGIT antibody domvanalimab and the anti-PD-1 antibody zimberelimab in patients with locally advanced unresectable or metastatic gastric (G), gastroesophageal junction (GEJ) or esophageal (E) adenocarcinoma. Patients in Arm A1, with previously untreated G/GEJ/E adenocarcinoma, received 1600 mg of domvanalimab intravenously (IV) every four weeks (Q4w) plus 480 mg of zimberelimab IV Q4W + FOLFOX (oxaliplatin 85 mg/m2 IV, leucovorin 400 mg/m2 IV, fluorouracil 400 mg/m2 IV bolus + 2400 mg/m2 continuous 46-48-hour IV infusion) every two weeks.