Domvanalimab and Zimberelimab in Phase 3 Trial for Upper GI Cancers

In a significant advancement for cancer treatment, the phase 3 clinical trial known as STAR-221 is set to evaluate the combination of domvanalimab and zimberelimab with chemotherapy for the first-line treatment of patients suffering from gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma. This trial follows promising results from the phase 2 EDGE-Gastric trial, which indicated a notable overall response rate of 59% among patients treated with this regimen.

The STAR-221 study, initiated in 2025, aims to compare the efficacy of the domvanalimab and zimberelimab combination against the established treatment of nivolumab plus chemotherapy. The objective is to assess overall survival (OS) rates among approximately 1,040 adult patients who are treatment-naive and present with locally advanced unresectable or metastatic upper gastrointestinal cancers. According to Dr. Zev A. Wainberg, a professor at UCLA and co-director of the UCLA GI Oncology Program, domvanalimab acts as an anti-TIGIT monoclonal antibody, enhancing immune activation against tumor cells when combined with PD-1 inhibitors like zimberelimab.

The EDGE-Gastric trial showcased the efficacy of this combination, revealing a complete response rate of 7% and a median duration of response of 12.4 months among patients. Key safety data indicated that while treatment-emergent adverse effects were reported in a significant number of patients, no serious adverse events were directly linked to the combined regimen of domvanalimab and zimberelimab.

Dr. Sam Klempner, a medical oncologist at Massachusetts General Hospital and an associate professor at Harvard Medical School, commented on the necessity for further investigation into this promising treatment strategy. The STAR-221 trial is crucial, as it aims to substantiate the benefits observed in the prior EDGE-Gastric study, particularly concerning overall survival metrics.

The primary completion date for the STAR-221 trial is estimated for December 2026, and the first data readout is expected in 2026. If the outcomes support a statistically significant improvement in OS, the combination of domvanalimab and zimberelimab could very well establish a new standard of care for patients diagnosed with these challenging malignancies. This trial represents a critical step in the ongoing battle against gastric and esophageal cancers, which have long been associated with high mortality rates and limited treatment options.