On December 19, 2022 Gilead Sciences, Inc. (Nasdaq: GILD) and Arcus Biosciences, Inc. (NYSE: RCUS) reported positive results from the fourth interim analysis of the 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. ARC-7 is a Phase 2, multicenter, three-arm, randomized, open-label study evaluating the combinations of Fc-silent anti-TIGIT monoclonal antibody domvanalimab plus anti-PD1 monoclonal antibody zimberelimab (doublet) and domvanalimab plus zimberelimab and etrumadenant, an A2a/b adenosine receptor antagonist (triplet), versus zimberelimab monotherapy. These results will be presented tomorrow during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Monthly Plenary Series,a new, virtual forum for presentation and discussion of the latest cancer research.

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"It is particularly encouraging to see that combination treatments may offer potentially meaningful advances for people with non-small cell lung cancer based on the largest, prospectively randomized Phase 2 study of anti-TIGIT and anti-PD1 antibodies to date," 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. "The preliminary improvements observed for each of the doublet and triplet regimens across multiple efficacy measures reinforce our confidence in the potential therapeutic benefit of inhibiting the TIGIT pathway and provide further support for the ongoing Phase 3 studies."

At the time of data cutoff, efficacy was evaluated in patients who had at least 13 weeks of follow-up and were therefore potentially eligible for at least two imaging scans (n=133), and safety was evaluated in all enrolled patients (n=149). With a median follow-up time for efficacy duration of approximately 12 months, both the doublet and triplet combinations demonstrated clinically meaningful improvements in median progression-free survival (PFS) and six-month landmark PFS rates compared to zimberelimab monotherapy, with a 45% reduction in risk of disease progression or death for the doublet and 35% for the triplet.

Each of the domvanalimab-containing study arms also demonstrated clinically meaningful improvements in objective response rate (ORR) compared to zimberelimab monotherapy. Confirmed ORR was 27%, 41% and 40% for the zimberelimab monotherapy arm and the domvanalimab-doublet and -triplet arms, respectively. While the triplet arm did not show an improvement over the doublet arm, it reinforces the results observed in the doublet arm, and the study will continue to monitor PFS, as well as overall survival, for the triplet arm as these data mature.

The efficacy results including ORR and PFS are summarized in the table below:

Endpoint

zimberelimab (Z)
monotherapy

(n=44)

domvanalimab +
zimberelimab (DZ)

(n=44)

etrumadenant +
domvanalimab +
zimberelimab (EDZ) (n=45)

Progression-free Survival (PFS)

Median in Months (95% CI)

5.4 (1.8, 9.6)

12.0 (5.5, NE)

10.9 (4.8, NE)

Hazard Ratio* (95% CI)

0.55 (0.31, 1.0)

0.65 (0.37, 1.1)

Six-month PFS rate (95% CI)

43% (27, 59)

65% (49, 80)

63% (48, 78)

Objective Response Rate (ORR)

ORR+ (95% CI)

27% (15.0, 42.8)

41% (26.3, 56.8)

40% (25.7, 55.7)

*Hazard ratio is for comparing domvanalimab-containing study arms to zimberelimab monotherapy.

+ Based on confirmed response per RECIST 1.1

NE=not evaluable
"Results from this randomized and controlled Phase 2 trial in a large number of patients validate the potential for an anti-TIGIT/anti-PD1 combination to improve outcomes for patients with metastatic NSCLC," said Dimitry S.A. Nuyten, M.D., Ph.D., Chief Medical Officer of Arcus Biosciences. "Arcus has been at the forefront of developing differentiated combination therapies, and these data are important for patients in need of potential new options, the oncology community’s understanding of TIGIT and for Arcus as a leader in the discovery and development of innovative therapeutics."

"As these data mature, we continue to see meaningful differentiation with domvanalimab across several measures of efficacy," said Bill Grossman, M.D., Ph.D., Senior Vice President, Therapeutic Area Head, Gilead Oncology. "These results reinforce the potential opportunity for anti-TIGIT treatments to provide benefit for people with lung cancer and other challenging tumors. We remain committed to accelerating our joint development program with Arcus across our four registrational Phase 3 studies."

No unexpected safety signals were observed across the three study arms at the time of data cutoff. The domvanalimab-containing study arms appeared to be generally well tolerated and showed an overall safety profile consistent with the known safety profiles of each individual molecule to date. Grade ≥3 treatment-emergent adverse events occurred in 58% of participants in the zimberelimab monotherapy study arm, 47% of the doublet arm, and 52% of the triplet arm. Incidence of infusion-related reactions was low across all treatment arms: 4%, 4% and 10% for zimberelimab monotherapy and the domvanalimab-doublet and -triplet arms, respectively. Immune-related adverse events, including the incidences and grades of rash and pruritus, were generally low and manageable with topical corticosteroids.

This interim analysis was conducted as of the clinical data cutoff date of August 31, 2022, with a total of 150 patients randomized across the three study arms. Patients in the study will continue to receive treatment per protocol, and an updated analysis including efficacy evaluation for all 150 patients is expected to be presented at the ASCO (Free ASCO Whitepaper) Annual Meeting in June 2023. The protocol-specified primary PFS analysis will be conducted later in 2023 once a specified number of events are achieved.

Domvanalimab, zimberelimab and etrumadenant are investigational molecules. Neither Gilead nor Arcus has received approval from any regulatory authority for any use globally, and their safety and efficacy for the treatment of lung cancer have not been established.

Webinar

At 5:00 p.m. Eastern Time / 2:00 p.m. Pacific Time on Tuesday, December 20, 2022, Gilead and Arcus executives will co-host a webinar to discuss the ARC-7 Plenary findings. The live webcast can be accessed via the Investor link on www.gilead.com or on www.arcusbio.com. The webinar will be archived for at least 30 days following the presentation.

About the ARC-7 Study

The ARC-7 study is a Phase 2, multicenter, three-arm, randomized, open-label study evaluating the safety and efficacy of anti-TIGIT antibody domvanalimab plus anti-PD1 antibody zimberelimab (doublet) versus domvanalimab plus zimberelimab and etrumadenant (triplet), an A2a/b adenosine receptor antagonist, versus zimberelimab monotherapy in 150 patients with first-line metastatic non-small cell lung cancer (NSCLC) 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 this interim analysis, 133 patients had at least 13 weeks of follow-up (potentially 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. ARC-7 is a proof of concept study to assess the safety and efficacy of domvanalimab-containing study arms over zimberelimab monotherapy. 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 cancer 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.