Domvanalimab Combination Shows Clinically Meaningful Progression-Free Survival in Lung Cancer

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Data from the fourth interim analysis of the ARC-7 trial shows that a combination of Fc-silent anti-TIGIT and anti-PD-1 molecules are effective for objective response rates in certain lung cancers.

Domvanalimab, an anti-TIGIT antibody, showed clinically meaningful results as an Fc-silent anti-TIGIT/anti-PD-1 combination therapy for patients with first-line metastatic non-small cell lung cancer (NSCLC) at a fourth interim analysis. Patients expressed a PD-L1 tumor proportion score (TPS) at 50% or more and had no epidermal growth factor receptor or anaplastic lymphoma kinase (EGFR/ALK) mutations.

“The efficacy measures observed, including [progression free survival] PFS, reinforce confidence in the TIGIT pathway. The interim results show that combining two checkpoint inhibitors—an anti-TIGIT and an anti-PD-1—delivered added benefit beyond anti-PD-1 monotherapy in this setting,” said Melissa L. Johnson, MD, director Lung Cancer Research, Sarah Cannon Research Institute at Tennessee Oncology, and Lead Investigator for the ARC-7 study, in a press release.

Objective response rates (ORR) and PFS were the primary efficacy measures, and combination therapies with domvanalimab measured higher in both at 6 months. Secondary measures were duration of response, disease control rate, overall survival, and overall safety.

Domvanalimab is designed to bind to immune cell protein receptor, TIGIT, a protein that is exploited by cancer cells because it stops an immune response. Domvanalimab, an Fc-silent investigational monoclonal antibody, binds to TIGIT and effectively activates immune cells to attack and kill target cells.

Researchers conducted this trial to determine the efficacy and safety of domvanalimab as a combination therapy against monotherapy with an anti-PD-1 antibody, zimberelimab.

The phase 2, multicenter, 3-arm, randomized open-label study evaluated the safety and efficacy of 3 different drug combinations in 1:1:1 randomized arms: domvanalimab and zimberelimab; domvanalimab, zimberelimab, and etrumadenant; and zimberelimab monotherapy in 150 patients with metastatic NSCLC (PD-L1 TPS greater than 50%, no EGFR or ALK mutations).

“The consistency of the efficacy and safety data from both of the domvanalimab-containing arms observed at this interim analysis support our continued strong conviction in the domvanalimab program,” said Dimitry S.A. Nuyten, MD, PhD, chief medical officer of Arcus Biosciences, in the press release.

Domvanalimab-combination arms were well tolerated, showed a consistent safety profile, and researchers observed no unexpected safety signals. It is currently being evaluated as a combination therapy for gastric, esophageal, and gastro-esophageal junction adenocarcinomas, as well as unselected NSCLC and unresectable Stage 3 NSCLC.

Data are expected to be presented at the American Society of Clinical Oncology (ASCO) Monthly Plenary Series on December 20, 2022.

“These results strengthen our belief in the potential of domvanalimab and the promise of our anti-TIGIT approach to meaningfully impact the outlook for people with metastatic lung cancer,” said Bill Grossman, MD, PhD, senior vice president, therapeutic area head, Gilead Oncology, in the press release.

Reference

Gilead Sciences, Inc. Gilead and Arcus Biosciences Announce Positive Update on Joint TIGIT Program From Interim Analysis of ARC-7 Study in Non-small Cell Lung Cancer. Businesswire. News Release. November 28, 2022. Accessed on November 29, 2022. https://www.businesswire.com/news/home/20221128005232/en