Anti-TIGIT Domvanalimab plus Anti-PD-1 Zimberelimab and Chemotherapy showed 26.7 months of Median Overall Survival as First-Line Treatment of Unresectable or Advanced Gastroesophageal Adenocarcinomas in the Phase 2 EDGE-Gastric Study
Arcus announced the first overall survival data from the ongoing phase II EDGE study in uGI cancer:
Anti-TIGIT Domvanalimab Plus Anti-PD-1 Zimberelimab and Chemotherapy Showed 26.7 Months of Median Overall Survival as First-Line Treatment of Unresectable or Advanced Gastroesophageal Adenocarcinomas in the Phase 2 EDGE-Gastric Study
This data is from the A1 arm of the study (PD-L1 positive population). This is only in phase 2 and there is no comparison. Nevertheless, 26.7 months is really good data in precisely the same population as the Phase 3 STAR-221 study, the registration study for Dom/Zim in uGI.
Domvanalimab is the rst and most clinically advanced Fc-silent investigational monoclonal antibody that is speci cally designed with Fc-silent properties to block and bind to the T-cell immunoreceptor with Ig and ITIM domains (TIGIT), a checkpoint receptor on immune cells that acts as a brake on the anticancer immune response. By binding to TIGIT with Fc-silent properties, domvanalimab is believed to work by freeing up immune-activating pathways and activate immune cells to attack and kill cancer cells without depleting the peripheral regulatory T cells important in avoiding immune-related toxicity.
Zimberelimab is an anti-programmed cell death protein-1 (PD-1) monoclonal antibody that binds PD-1, with the goal of restoring the antitumor activity of T cells. Zimberelimab has demonstrated high a nity, selectivity and potency in various tumor types.
- EDGE-Gastric Study
The ongoing, multi-arm, multi-cohort global Phase 2 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 1600mg of domvanalimab intravenously (IV) every four weeks (Q4W) plus 480mg of zimberelimab IV Q4W + FOLFOX (oxaliplatin 85 mg/m2 IV, leucovorin 400mg/m2 IV, uorouracil 400mg/m2 IV bolus + 2400mg/m2 continuous 46-48-hour IV infusion) every two weeks.
- STAR-221 Study
The ongoing, global STAR-221 trial (NCT05568095) enrolled approximately 1,050 participants with locally advanced unresectable or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma. The primary endpoints of the study are overall survival in PD-L1-high tumors, PD-L1-positive tumors and in the intent-to-treat population (all PD-L1 levels); secondary endpoints include progression-free survival, objective response rate and duration of response. Participants were randomized 1:1 between two arms: 1600mg of domvanalimab intravenously (IV) every four weeks plus 480mg of zimberelimab IV every four weeks plus FOLFOX (oxaliplatin, leucovorin, uorouracil) every two weeks or 1200mg of domvanalimab plus 360mg of zimberelimab every three weeks plus CAPOX (capecitabine and oxaliplatin) every three weeks 240mg of nivolumab IV every two weeks plus FOLFOX every two weeks or 360mg of nivolumab plus CAPOX every three weeks