Early findings from the phase II EDGE-Gastric trial indicate the potential for two novel agents to make a difference in advanced gastroesophageal adenocarcinoma, according to findings reported at the ASCO Plenary Series: November 2023 Session by Yelena Y. Janjigian, MD, Chief of the Gastrointestinal Oncology Service at Memorial Sloan Kettering Cancer Center (Abstract 433248).
EDGE-Gastric is a multiarm trial exploring the addition of two investigational therapies—domvanalimab, a monoclonal antibody targeting anti–T-cell immunoglobulin and ITM domain (TIGIT), and zimberelimab, a PD-1 inhibitor—to fluorouracil, leucovorin, and oxliplatin (FOLFOX) as first-line treatment for locally advanced unresectable or metastatic gastric/gastroesophageal junction/esophageal adenocarcinoma. The study is evaluating three cohorts based on previous treatment and line of therapy. Dr. Janjigian reported the first efficacy and safety results of Arm A1.
“The addition of domvanalimab and zimberelimab to FOLFOX shows encouraging objective response rates and 6-month progression-free survival in advanced gastroesophageal adenocarcinoma, irrespective of PD-L1 expression,” Dr. Janjigian said.
Yelena Y. Janjigian, MD
As Dr. Janjigian explained, a PD-1 inhibitor combined with front-line chemotherapy is currently the standard of care in metastatic gastroesophageal cancer, but patients typically develop resistance to this regimen. EDGE-Gastric is evaluating the potential benefit of inhibiting TIGIT, an immune receptor present on some T cells and natural killer cells. “Dual anti–PD-1 and anti–TIGIT increases tumor antigen–specific CD8+ T-cell expansion, with potent preclinical antitumor activity,” she said.
About EDGE-Gastric
The phase II study enrolled 120 patients with previously untreated locally advanced unresectable or metastatic gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma. In the Arm A1 cohort, 41 patients received first-line therapy with domvanalimab, zimberelimab, and FOLFOX for a median of 33 weeks. The primary endpoints are investigator-assessed objective response rate and safety.
In the Arm A1 cohort, PD-L1 tumor area positivity score was < 5% in 59% of patients, and ≥ 5% or unknown in the remainder. Most patients (59%) had microsatellite-stable tumors, and only 2% were known to be microsatellite instability–high.
Encouraging Efficacy and Safety
The intent-to-treat objective response rate for all patients on the study was 59%; the median progression-free survival was not reached; and the progression-free survival rate was 77% at 6 months. In patients with high PD-L1 expression (≥ 5%), the response rate was 80%, with one complete response seen, Median progression-free survival was not reached, and 93% of patients were progression-free at 6 months, Dr. Janjigian reported.
Serious treatment-related side effects occurred in 24% of patients, with 5% of them being drug-related. Grade ≥ 3 treatment-related adverse events related to any study drug occurred in 56% of patients, with 49% of patients discontinuing a study drug because of this. Immune-mediated adverse events were uncommon and generally mild.
“The incidence of adverse events was similar to prior experience with anti–PD-1 plus FOLFOX and there were no new safety concerns identified,” she said.
Next Steps
Dr. Janjigian said that these results led to the phase III STAR-221 trial (ClinicalTrials.gov identifier NCT05568095), which is currently comparing domvanalimab and zimberelimab plus chemotherapy against nivolumab plus chemotherapy as a first-line treatment in locally advanced unresectable or metastatic gastric, gastroesophageal junction, and esophageal adenocarcinoma. The study is currently recruiting patients across five continents.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
