Anti-TIGIT domvanalimab + zimberelimab and chemotherapy exceeded one year of median progression-free survival as a first-line treatment For upper GI cancers

The ongoing, multi-arm, global Phase II EDGE-Gastric study is evaluating the safety and efficacy of various combinations of the Fc-silent anti-TIGIT antibody domvanalimab plus the anti-PD-1 monoclonal antibody zimberelimab and chemotherapy in this patient population. These results will be presented during the American Society of Clinical Oncology (ASCO) Plenary Series: Rapid Abstract Updates session by Yelena Y. Janjigian, M.D., Chief, Gastrointestinal Oncology, Memorial Sloan Kettering Cancer Center, and a principal investigator for the EDGE-Gastric study (Abstract 433 248).

“I am encouraged to see that patients treated with domvanalimab plus zimberelimab and chemotherapy had a median progression-free survival beyond one year, which exceeds the historical benchmarks for anti-PD-1 plus chemotherapy alone,” said Dr. Janjigian. “Notably, nearly 60% of patients in the EDGE-Gastric study achieved progression-free survival at 12 months. These promising results reinforce our confidence in the ongoing Phase 3 STAR-221 study, which evaluates the same regimen in the same patient population and has the potential to address a high unmet need for people with these cancers.”

At data cutoff (DCO, March 12, 2024), safety and efficacy were evaluated in all patients enrolled and treated (n=41). With a median time on treatment of 49.4 weeks (range: 0.4 - 79.4 weeks), the domvanalimab plus zimberelimab and chemotherapy regimen demonstrated sustained improvement across efficacy measures, including in those patients who have low PD-L1 expression.

The domvanalimab-containing regimen showed an ORR of 80% in patients with PD-L1-high tumors (tumor activity positivity (TAP) (greater than 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 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 six-month PFS rate was 93% and 68% for subjects with PD-L1-high and PD-L1-low tumours respectively.

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.