On November 28, 2022 Gilead Sciences, Inc. (Nasdaq: GILD) and Arcus Biosciences (NYSE: RCUS) reported a positive update from the fourth interim analysis of the randomized, open-label Phase 2 ARC-7 study in patients with first-line metastatic non-small cell lung cancer (NSCLC) with PD-L1 tumor proportion score (TPS) ≥50% without epidermal growth factor receptor or anaplastic lymphoma kinase (EGFR/ALK) mutations (Press release, Gilead Sciences, NOV 28, 2022, View Source [SID1234624498]). ARC-7 is evaluating the combinations of anti-TIGIT antibody domvanalimab plus anti-PD-1 antibody zimberelimab (doublet), and domvanalimab plus zimberelimab and etrumadenant, an A2a/b adenosine receptor antagonist (triplet), versus zimberelimab alone, and represents the first randomized Phase 2 study of an Fc-silent anti-TIGIT/anti-PD-1 combination. The protocol-specified fourth interim analysis was conducted when the trial reached full enrollment, with a clinical data cutoff date of August 31, 2022. A total of 150 patients have been randomized across the three study arms.
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For the current interim analysis, efficacy was evaluated in study patients who had at least 13 weeks of potential follow-up and were eligible for at least two imaging scans (n=133). Both domvanalimab combinations continued to show clinically meaningful differentiation compared to zimberelimab monotherapy across multiple efficacy measures, including objective response rates (ORR), progression-free survival (PFS) and six-month landmark PFS.
"The efficacy measures observed, including 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, M.D., Director Lung Cancer Research, Sarah Cannon Research Institute at Tennessee Oncology, and Lead Investigator for the ARC-7 study. "These data are important for the lung cancer research field, and I look forward to presenting the dataset at the upcoming virtual ASCO (Free ASCO Whitepaper) Monthly Plenary on December 20th."
At time of data cutoff, no unexpected safety signals were observed across the three study arms. Both domvanalimab-containing arms were generally well tolerated and showed an overall safety profile consistent with the known safety profiles for each individual molecule to date.
"We are thrilled that Dr. Melissa Johnson will present the full results for the current interim analysis of ARC-7, including ORR, PFS and disease control rate, in the coming weeks, given the importance of these data for the immuno-oncology field," said Dimitry S.A. Nuyten, M.D., Ph.D., Chief Medical Officer of Arcus Biosciences. "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."
"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, M.D., Ph.D., Senior Vice President, Therapeutic Area Head, Gilead Oncology. "We will continue to accelerate our TIGIT development program with Arcus, with four ongoing registrational studies in NSCLC and upper GI malignancies."
Detailed results from this fourth interim analysis and an exploratory analysis on 12 patients who crossed over from zimberelimab monotherapy arm to triplet therapy will be presented on December 20, 2022, at the Monthly Plenary Series, a new virtual forum for presentation and discussion of the latest cancer research. According to ASCO (Free ASCO Whitepaper), live presentations are accessible to virtual attendees and available on-demand, and abstract presentations are accompanied by a discussant presentation and followed by a live Q&A session. Abstracts accepted for the Monthly Plenary Session are also placed at the ASCO (Free ASCO Whitepaper) Annual Meeting in June 2023. During the ASCO (Free ASCO Whitepaper) Annual Meeting, additional results from further analysis of the ARC-7 dataset will be presented.
Domvanalimab, zimberelimab and etrumadenant are investigational molecules and neither Arcus or Gilead have received approval from any regulatory authority for any use globally, including for the treatment of lung cancer. Their efficacy and safety for the treatment of lung cancer have not been established.
About the ARC-7 Study
The ARC-7 study is a Phase 2, multicenter, 3-arm, randomized open-label study evaluating the safety and efficacy of anti-TIGIT antibody domvanalimab plus anti-PD-1 antibody zimberelimab (doublet) versus domvanalimab plus zimberelimab and etrumadenant (triplet), an A2a/b adenosine receptor antagonist, versus zimberelimab alone in 150 patients with first-line metastatic non-small cell lung cancer with PD-L1 TPS ≥50% and no EGFR or ALK mutations. Patients are randomized 1:1:1 across the three study arms, and patients who progress on zimberelimab monotherapy may cross over to receive the triplet. At the time of the fourth interim analysis, 133 patients had at least 13 weeks of potential follow-up (eligible for at least two tumor assessments). The co-primary endpoints are objective response rate and progression-free survival per Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Secondary endpoints include duration of response, disease control rate, overall survival and safety. More information about ARC-7 is available at View Source
About Domvanalimab
Domvanalimab is an Fc-silent investigational monoclonal antibody that is designed to bind to TIGIT, a protein receptor on immune cells that acts as a brake on the immune response. Cancer cells can exploit TIGIT to avoid detection by the immune system. By binding to TIGIT, domvanalimab is expected to free up immune activating pathways and activate immune cells to attack and kill targeted cells. Domvanalimab is being evaluated in four registrational Phase 3 studies across lung and gastrointestinal cancers, including: (1) ARC-10, evaluating domvanalimab plus zimberelimab versus pembrolizumab in first-line locally advanced or metastatic PD-L1 ≥50% NSCLC; (2) PACIFIC-8, being operationalized by AstraZeneca, evaluating domvanalimab plus durvalumab in unresectable Stage 3 NSCLC; (3) STAR-121, evaluating domvanalimab plus zimberelimab and chemotherapy versus pembrolizumab plus chemotherapy in first-line PD-L1 unselected NSCLC; and (4) STAR-221, evaluating domvanalimab plus zimberelimab and chemotherapy versus nivolumab plus chemotherapy in first-line locally advanced, unresectable or metastatic gastric, esophageal and gastro-esophageal junction adenocarcinomas.