The combination of domvanalimab with zimberelimab and chemotherapy generated an encouraging overall response rate and 6-month progression-free survival rate among patients with locally advanced unresectable or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma, according to findings from cohort A1 of the ongoing phase 2 EDGE-Gastric study.
The results, presented by Yelena Y. Janjigian, MD, during the ASCO Plenary Series: November 2023 Session, showed that as of the data cutoff date of September 4, 2023, a total of 41 patients were enrolled and treated with a median follow-up of 8.1 months. Twenty-four patients (59%) remained on study treatment at this time, with a median time on treatment of 33 weeks.
Efficacy Results Show Promise Across PD-L1 Expression Levels
The combination demonstrated differential efficacy based on PD-L1 expression status. Patients with PD-L1-high tumors achieved an overall response rate of 80% (95% CI, 52-96), while patients with PD-L1-low tumors had an ORR of 46% (95% CI, 26-67). For patients overall, the ORR was 59% (95% CI, 42-74), with 2 confirmed complete responses observed.
"The addition of domvanalimab and zimberelimab to FOLFOX shows encouraging overall response rate and 6-month PFS in the firstline for patients with advanced gastroesophageal adenocarcinoma, irrespective of PD-L1 expression," said Janjigian, a medical oncologist and chief of the Gastrointestinal Oncology Service at Memorial Sloan Kettering Cancer Center.
Six-month progression-free survival rates were particularly impressive, reaching 93% for patients with PD-L1-high tumors (95% CI, 81-100), 68% for patients with PD-L1-low tumors (95% CI, 48-88), and 77% for patients overall (95% CI, 64-90). The median PFS was not reached, with mature PFS data anticipated to be released in the second half of 2024.
Safety Profile Remains Manageable
The domvanalimab-containing regimen showed a similar safety profile to what has been previously seen for anti-PD-1 plus chemotherapy in this setting. The combination was well-tolerated, with the most common adverse events including neutropenia (59%), nausea (54%), anemia (27%) and fatigue (27%).
Twenty percent of patients experienced an infusion-related reaction; however, most (17%) were related to chemotherapy. Notably, no serious immune-mediated adverse events were experienced by any patient in the study, and no treatment-emergent adverse events resulted in death.
"There were no new safety signals and no new treatment-related deaths...AE incidence was similar to prior experience with anti-PD-1 plus FOLFOX," explained Janjigian.
Study Design and Patient Population
EDGE-Gastric is an ongoing, multi-arm, global, phase 2 study evaluating the safety and efficacy of domvanalimab, an Fc-silent anti-TIGIT antibody, plus zimberelimab, an anti-PD-1 antibody, with and without chemotherapy for the treatment of patients with locally advanced unresectable or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma.
Patients received 1600 mg of domvanalimab intravenously every 4 weeks plus 480 mg of zimberelimab intravenously every 4 weeks, and chemotherapy consisting of oxaliplatin 85 mg/m2 IV, leucovorin 400 mg/m2 IV, fluorouracil 400 mg/m2 IV bolus and 2400 mg/m2 continuous 46-48-hour IV infusion every 2 weeks.
The mean age of patients was 61 years (range, 30-82), with 24 patients being male. Twenty-two patients were from the United States or France, while 19 were from Korea. Twenty-four (59%) patients had an ECOG performance status of 1, and 24 (59%) patients had MSS/MSI-low status.
Broader Development Program
These data from cohort A1 add to the growing body of evidence that domvanalimab has encouraging and differentiated safety and tolerability profiles. In addition to EDGE-Gastric, three additional phase 3 registrational studies are ongoing and assessing domvanalimab-containing regimens in lung cancer, including STAR-121, ARC-10, and PACIFIC-8. These preliminary data also support the ongoing STAR-221 trial in unresectable or metastatic upper gastrointestinal cancers.
