On June 3, 2023 Gilead Sciences, Inc. (Nasdaq: GILD) and Arcus Biosciences, Inc. (NYSE: RCUS) reported updated results from an 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 (EGFR) or anaplastic lymphoma kinase (ALK) mutations. ARC-7 is the first Phase 2, randomized, open-label study evaluating the combinations of Fc-silent anti-TIGIT monoclonal antibody domvanalimab plus anti-PD-1 monoclonal antibody zimberelimab (doublet) and domvanalimab plus zimberelimab and etrumadenant, an A2a/b adenosine receptor antagonist (triplet), versus zimberelimab monotherapy (Press release, Gilead Sciences, JUN 3, 2023, View Source [SID1234632428]). These results will be presented today during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Plenary Series: Rapid Abstract Updates session by Melissa L. Johnson, M.D., Director, Lung Cancer Research, Sarah Cannon Research Institute, and Lead Investigator for the ARC-7 study.

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"Progression-free survival curves showed early separation of both domvanalimab-containing arms from the zimberelimab arm, which was consistently maintained, and supports the potential therapeutic benefit of inhibiting the TIGIT pathway," said Melissa L. Johnson, M.D., Director, Lung Cancer Research, Sarah Cannon Research Institute, and Lead Investigator for the ARC-7 study. "I was also encouraged by the consistency of meaningful improvements across other outcome measures for the domvanalimab-containing arms. I look forward to continuing to work with Gilead and Arcus on the dom-zim combinations."

At the time of data cutoff (DCO), February 7, 2023, safety and efficacy were evaluated in all patients randomized and treated (n=150). With a median follow-up time of approximately 18 months, both domvanalimab-containing study arms demonstrated sustained, clinically meaningful improvements in progression-free survival (PFS) compared to zimberelimab monotherapy, with a 33% reduction in risk of disease progression or death for the doublet and 28% for the triplet.

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

Endpoint

zimberelimab (Z)
monotherapy
(n=50)

domvanalimab +
zimberelimab
(DZ)
(n=50)

etrumadenant +
domvanalimab +
zimberelimab
(EDZ) (n=50)

Progression-Free Survival (PFS)

Median in Months (95% CI)

5.4 (2.7, 9.7)

9.3 (4.1, NE)

9.9 (4.8, 14.6)

Hazard Ratio* (95% CI)

0.67 (0.4, 1.13)

0.72 (0.63, 1.8)

Six-month PFS rate (95% CI)

45% (30, 59)

58% (43, 72)

62% (48, 76)

12-month PFS rate (95% CI)

25% (11, 40)

41% (26, 56)

44% (29, 59)

Objective Response Rate (ORR)

ORR+ Confirmed + Pending (95% CI)

15 (30%)

[17.9%, 44.6%]

20 (40%)++

[26.4%, 54.8%]

22 (44%)

[30%, 58.7%]

Complete Response

1 (2%)

1 (2%)

0 (0%)

Partial Response Confirmed

14 (28%)

18 (36%)

22 (44%)

Partial Response Pending

0 (0%)

1 (2%)

0 (0%)

Stable Disease

16 (32%)

18 (36%)

16 (32%)

Progressive Disease

12 (24%)

4 (8%)

7 (14%)

Not Evaluable (NE)

7 (14%)

8 (16%)

5 (10%)

CI=Confidence Interval
*

Comparing DZ and EDZ arms to Z monotherapy.

+

Per RECIST 1.1

++

Across all arms, one participant in the DZ arm had a response pending confirmation, which was confirmed after DCO date.

–

Preliminary duration of response (DoR) analyses favor domvanalimab-containing arms, with median DoR (range, ‘+’: censored) as follows: Z: 13.2mo (+1.4-+19.4), DZ: not reached (2.8-+26.6), EDZ: 23.7mo (2.6-23.7).

–

As of the DCO, approximately twice as many participants remain on study treatment in the domvanalimab-containing arms compared to zimberelimab monotherapy [Z: (n=9), DZ: (n=17), EDZ: (n=20)].

–

Consistent ORR and PFS improvements were shown for the domvanalimab-containing arms in a post-hoc analysis of centrally confirmed PD-L1-high patients.

"At this analysis, the domvanalimab-containing study arms continued to show improved efficacy across multiple measures and both the doublet and triplet arms were generally well tolerated," said Dimitry S.A. Nuyten, M.D., Ph.D., Chief Medical Officer of Arcus Biosciences. "These data reinforce our confidence in the domvanalimab program."

"The ARC-7 proof-of-concept study has critically advanced our understanding of the activity of domvanalimab, the first Fc-silent anti-TIGIT monoclonal antibody in pivotal trials," said Bill Grossman, M.D., Ph.D., Senior Vice President, Therapeutic Area Head, Gilead Oncology. "We look forward to quickly advancing our four ongoing Phase 3 registrational programs in NSCLC and upper GI cancers."

No unexpected safety signals were observed across the three study arms at the time of DCO. 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. Incidence of infusion-related reactions was low across all treatment arms: 4%, 4% and 12% for zimberelimab monotherapy and the domvanalimab-doublet and -triplet arms, respectively. The addition of domvanalimab to zimberelimab did not increase the incidence of infusion-related reactions, consistent with the Fc-silent design of domvanalimab.

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.

About the ARC-7 Study

The ARC-7 study is the first Phase 2, multicenter, three-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 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, 150 patients had a median follow-up of 18.5 months. 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 the first Fc-silent investigational monoclonal antibody in pivotal trials that is designed to block and bind to the T-cell immunoreceptor with Ig and ITIM domains (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 has demonstrated complete receptor coverage on all TIGIT-expressing peripheral leukocytes.

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.