Arcus Biosciences: Domvanalimab and Zimberelimab Boost Survival in PD-L1-High Lung Cancer Study

HAYWARD, Calif.--(BUSINESS WIRE)--Arcus Biosciences, Inc. (NYSE:RCUS), a global biopharmaceutical company in the clinical stage, is engaged in developing distinct molecules and combination therapies for cancer patients. The company recently revealed findings from Part 1 of ARC-10, a randomized, open-label, three-arm study. This study assessed the efficacy of domvanalimab, an Fc-silent anti-TIGIT monoclonal antibody, coupled with zimberelimab, an anti-PD-1 monoclonal antibody (DZ), against zimberelimab alone (Z) or chemotherapy. The trial focused on patients with locally advanced or metastatic squamous or non-squamous non-small cell lung cancer (NSCLC) that exhibited a PD-L1 tumor proportion score (TPS) of 50% or more and lacked any tumor genomic aberration or driver mutation for which a targeted therapy is approved. Conducted in collaboration with Gilead Sciences, the outcomes will be presented on November 8 during a late-breaking poster session at the Society for Immunotherapy of Cancer (SITC) 2024 Annual Meeting by Dr. Melissa L. Johnson, Director of the Lung Cancer Research Program at the Sarah Cannon Research Institute, and investigator for the ARC-10 study.

Dr. Melissa L. Johnson stated, "Domvanalimab plus zimberelimab showed a significant improvement in overall survival compared to zimberelimab alone, with a reduction in the risk of death by 36% and a median overall survival expected to surpass two years." She emphasized that the findings further support the potential benefits of inhibiting both TIGIT and PD-1 pathways over solely targeting the PD-1 pathway.

Dr. Dimitry Nuyten, the chief medical officer of Arcus, highlighted that these are the initial results showing an enhancement in overall survival for the domvanalimab and zimberelimab combination. He added that these results contribute to the growing evidence indicating that domvanalimab, as an Fc-silent anti-TIGIT antibody, may offer a differentiated efficacy, safety, and tolerability profile compared to Fc-enabled anti-TIGIT antibodies based on published data.

As of the data cutoff on May 17, 2024, 98 patients were randomized, and 95 received treatment in Part 1 of the study. The median follow-up period was 24.5 months, with 22 patients still undergoing treatment (11 in the DZ group, 10 in the Z group, and 1 in the chemotherapy group). Patient baseline demographics were generally balanced across the study arms, although there was a slight imbalance with more patients having adenocarcinoma, ECOG status 0, and brain metastasis favoring the chemotherapy arm. Here is a summary of the efficacy results:

- Overall Survival (OS): The median OS for the DZ group was not reached (13.7-NE), 24.4 months (7.8-NE) for the Z group, and 11.9 months (2.7-NE) for the chemotherapy group.
- Hazard Ratios for DZ vs Z was 0.64 (0.32-1.25), DZ vs chemotherapy was 0.43 (0.20, 0.93), and Z vs chemotherapy was 0.63 (0.30-1.29).
- 12-Month Survival Rates were 68% for DZ, 57% for Z, and 50% for chemotherapy.
- Progression-Free Survival (PFS): Median PFS was 11.5 months (4.0-26.2) for DZ, 6.2 months (2.5-12.3) for Z, and 9.6 months (2.6-16.4) for chemotherapy.
- Objective Response Rate: 44.7% for DZ, 35.0% for Z, and 35.3% for chemotherapy.

DZ and Z were generally well tolerated with no new safety issues identified at the data cutoff. Treatment-related adverse events (TRAEs) leading to treatment discontinuation were higher for chemotherapy (23.5%) compared to DZ (10.5%) and Z (7.5%). Incidences of infusion-related reactions were low across all groups. Grade 3 or higher TRAEs were more frequent for chemotherapy (47.1%) compared to DZ (21.1%) and Z (15.0%). TRAEs resulting in death were lower for DZ (2.6%) compared to Z (10.0%) and chemotherapy (11.8%).

The ARC-10 study originally started as a randomized Phase 3 trial and was later revised to assess domvanalimab plus zimberelimab against pembrolizumab in its second part. Part 1 focused on patients with advanced NSCLC, lacking specific genomic aberrations or mutations. Patients were randomized into three arms receiving domvanalimab plus zimberelimab, zimberelimab alone, or platinum doublet chemotherapy every three weeks. The primary endpoint was PFS, with secondary endpoints including overall survival, confirmed objective response rate, and safety.

Domvanalimab is an Fc-silent investigational monoclonal antibody designed to block TIGIT, a checkpoint receptor that impairs the anticancer immune response. By inhibiting TIGIT, domvanalimab aims to activate immune cells to target and destroy cancer cells without causing immune-related toxicity. When combined with PD-1 inhibition, the dual blockade is believed to enhance immune cell activation significantly.

Zimberelimab, an anti-PD-1 monoclonal antibody, aims to restore the anti-tumor activity of T cells and is being evaluated for various cancers in combination with other immunotherapies. While approved in China for certain cancers, zimberelimab remains investigational outside of China.

Arcus Biosciences, founded in 2015, is dedicated to developing innovative cancer therapies and has multiple investigational medicines in clinical trials.