Domvanalimab-Containing Regimen Shows Positive Preliminary Data for Upper Gastrointestinal Cancers

Domvanalimab (Gilead Sciences Inc, Arcus Biosciences Inc) plus zimberelimab (Arcus Biosciences Inc) with chemotherapy demonstrated a positive overall response rate (ORR) and 6-month progression free survival (PFS) rate for patients with upper gastrointestinal (GI) cancers, according to preliminary results from the Arm A1 of the EDGE-Gastric study (NCT05329766).

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The EDGE-Gastric study is an ongoing phase 2 multi-arm, global trial evaluating the safety and efficacy of various combinations of domvanalimab plus zimberelimab and chemotherapy for those with locally advanced unresectable or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma. The results were presented at the American Society of Clinical Oncology Monthly Plenary Series.

“The preliminary data from the EDGE-Gastric study underscore the potential role of dual anti-TIGIT and anti-PD-1-containing regimen in the treatment of gastroesophageal cancer where front-line chemotherapy with anti-PD-1 blockade is currently the standard,” Yelena Y. Janjigian, MD, chief attending physician of the Gastrointestinal Medical Oncology Service at Memorial Sloan Kettering Cancer Center, said in a press release. “These early data are encouraging and indicate the potential for the anti-TIGIT, domvanalimab-based therapy to improve upon anti-PD-1 and chemotherapy in this setting, with a similar safety profile to anti-PD-1 and chemotherapy.”

Investigators of the study enrolled 41 individuals, with a median follow-up time of 8.1 months. Approximately 59% of individuals remained on the study treatment as of the data cutoff of September 4, 2023, with a median time on treatment of 33 weeks. Patients in Arm A1 were previously untreated and received 1600 mg of domvanalimab intravenously every 4 weeks plus 480 mg of zimberelimab intravenously every 4 weeks, and oxaliplatin 85 mg/m2 intravenously, leucovorin 400 mg/m2 intravenously, fluorouracil 400 mg/m2 bolus and 2400 mg/m2 continuous 46 to 48-hour infusion continuous (Folfox) every 2 weeks, according to the press release.

The results of the study demonstrated an ORR of 59%, with 80% in those with PD-L1-high tumors and 46% in those with PD-L1-low tumors. There were 2 confirmed complete responses in the study, according to the data.

The PFS rate at 6 months was 77% overall for patients, with 93% for PD-L1-high tumors and 68% for PD-L1-low tumors. At this time of data cut-off, the median PFS was not reached and investigators expect mature PFS data by the second half of 2024.

The combination was also well tolerated, with a similar safety profile as reported for other anti-PD-1 drugs plus chemotherapy for this setting, according to the press release. The most common adverse events (AEs) included neutropenia, nausea, anemia, and fatigue. The investigators also reported that 20% of individuals experienced infusion-related reactions with 17% being related to chemotherapy. There were no serious immune-related AEs, according to the results, and there were no treatment-emergence AEs that resulted in death.

Investigators said the preliminary data from the Arm A1 part of the phase 2 study supports the current, ongoing phase 3 STAR-221 study (NCT05568095), which is currently evaluating unresectable or metastatic upper GI cancers. Both Gilead and Arcus Biosciences have 3 additional phase 3 studies of domvanalimab-containing regimens for lung cancer treatment, which includes STAR-121, ARC-10 (NCT04736173), and PACIFIC-8.

Domvanalimab and zimberelimab are currently investigational molecules and have not received approval from any regulatory authority for any use globally, according to the press release.

Reference

Gilead and Arcus announce new data showing encouraging clinical activity of Anti-TIGIT domvanalimab-containing regimen as first-line treatment for upper GI cancers. News release. Gilead Sciences. November 6, 2023. Accessed November 7, 2023. https://www.gilead.com/news-and-press/press-room/press-releases/2023/11/gilead-and-arcus-announce-new-data-showing-encouraging-clinical-activity-of-anti-tigit-domvanalimab-containing-regimen-as-first-line-treatment-for-upp