– Data Support the Ongoing Phase 3 STAR-221 Study of Domvanalimab Plus Zimberelimab and Chemotherapy, Potentially the First Anti-TIGIT Combination to Market for These Cancers –

– Results will be Presented Today During an Oral Session at the ASCO Annual Meeting –

FOSTER CITY, CA & HAYWARD, CA, USA I June 01, 2024 I Gilead Sciences, Inc. (Nasdaq: GILD) and Arcus Biosciences, Inc. (NYSE: RCUS) today announced longer-term efficacy and safety results from Arm A1 of the Phase 2 EDGE-Gastric study. These updated data show consistent objective response rate (ORR) and provide mature progression-free survival (PFS) in patients with locally advanced unresectable or metastatic gastric, gastroesophageal junction or esophageal adenocarcinoma (upper GI cancers). The ongoing, multi-arm, global Phase 2 EDGE-Gastric study is evaluating the safety and efficacy of various combinations of the Fc-silent anti-TIGIT antibody domvanalimab plus the anti-PD-1 monoclonal antibody zimberelimab and chemotherapy in this patient population. These results will be presented today during the American Society of Clinical Oncology (ASCO) Plenary Series: Rapid Abstract Updates session by Yelena Y. Janjigian, M.D., Chief, Gastrointestinal Oncology, Memorial Sloan Kettering Cancer Center, and a principal investigator for the EDGE-Gastric study (Abstract 433248).

“I am encouraged to see that patients treated with domvanalimab plus zimberelimab and chemotherapy had a median progression-free survival beyond one year, which exceeds the historical benchmarks for anti-PD-1 plus chemotherapy alone,” said Dr. Janjigian. “Notably, nearly 60% of patients in the EDGE-Gastric study achieved progression-free survival at 12 months. These promising results reinforce our confidence in the ongoing Phase 3 STAR-221 study, which evaluates the same regimen in the same patient population and has the potential to address a high unmet need for people with these cancers.”

At data cutoff (DCO, March 12, 2024), safety and efficacy were evaluated in all patients enrolled and treated (n=41). With a median time on treatment of 49.4 weeks (range: 0.4 – 79.4 weeks), the domvanalimab plus zimberelimab and chemotherapy regimen demonstrated sustained improvement across efficacy measures, including in those patients who have low PD-L1 expression.

Summary of efficacy results:

n=41(TAP ≥5%)(TAP <5%)
Progression-Free Survival (PFS)   
Median in Months (95% CI)12.9 mos (9.8, 13.8)13.8 mos (11.3, NE)11.3 mos (5.5, 13.8)
12-month PFS Rate (95% CI)57.6% (41.7,73.5)68.8% (46.0, 91.5)46.8% (24.7, 68.9)
Objective Response Rate (ORR) per RECIST v1.1   
Confirmed ORR (95% CI)58.5% (42.1, 73.7)68.8% (41.3, 89.0)50.0% (29.1, 70.9)
Complete Response3 (7.3%)1 (6.3%)1 (4.2%)
Partial Response21 (51.2%)10 (62.5%)11 (45.8%)
Stable Disease14 (34.1%)5 (31.3%)9 (37.5%)
Progressive Disease Confirmed2 (4.9%)02 (8.3%)
Not Evaluable**1 (2.4%)01 (4.2%)
Median Duration of Response (DOR) in Months12.4 mos (9.9, NE)NE (11.5, NE)10.2 mos (4.0, 12.4)
*One subject with no tissue available for central PD-L1 testing. From local lab results, the subject is PD-L1 low via 22-C3 assay. This subject achieved confirmed complete response.
** One subject has no post baseline scans.
CI: confidence interval
NE: not evaluable
TAP: tumor area positivity

No unexpected safety signals were observed at the time of DCO. The domvanalimab plus zimberelimab and chemotherapy regimen was generally well tolerated and showed an overall safety profile consistent with the known safety profiles of each individual molecule to date. Infusion-related reactions were observed in 19.5% of the total subjects, and the majority were related to chemotherapy.

The updated data from Arm A1 of the Phase 2 EDGE-Gastric study support the ongoing Phase 3 STAR-221 study, in unresectable or metastatic upper GI cancers, which is expected to complete enrollment mid-year 2024.

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

About the EDGE-Gastric Study

The ongoing, multi-arm, multi-cohort global Phase 2 EDGE-Gastric trial (NCT05329766) is evaluating the safety and efficacy of various combinations of the Fc-silent anti-TIGIT antibody domvanalimab and the anti-PD-1 monoclonal antibody zimberelimab in patients with locally advanced unresectable or metastatic gastric (G), gastroesophageal junction (GEJ) or esophageal (E) adenocarcinoma. Patients in Arm A1, with previously untreated G/GEJ/E adenocarcinoma, received 1600 mg of domvanalimab intravenously (IV) every four weeks (Q4W) plus 480 mg of zimberelimab IV Q4W + FOLFOX (oxaliplatin 85 mg/m2 IV, leucovorin 400 mg/m2 IV, fluorouracil 400 mg/m2 IV bolus + 2400 mg/m2 continuous 46-48-hour IV infusion) every two weeks.

About Domvanalimab

Domvanalimab is the first and most clinically advanced Fc-silent investigational monoclonal antibody that is specifically designed with Fc-silent properties to block and bind to the T-cell immunoreceptor with Ig and ITIM domains (TIGIT), a checkpoint receptor on immune cells that acts as a brake on the anticancer immune response. By binding to TIGIT with Fc-silent properties, domvanalimab is believed to work by freeing up immune-activating pathways and activate immune cells to attack and kill cancer cells without depleting the peripheral regulatory T cells important in avoiding immune-related toxicity.

Combined inhibition of both TIGIT and programmed cell death protein-1 (PD-1) is believed to significantly enhance immune cell activation, as these checkpoint receptors play distinct, complementary roles in anti-tumor activity. Domvanalimab is being evaluated in combination with anti-PD-1 monoclonal antibodies, including zimberelimab, as well as other investigational cancer immunotherapies and A2a/A2b adenosine receptor antagonist etrumadenant, in multiple ongoing and planned early and late-stage clinical studies in various tumor types.

About Zimberelimab

Zimberelimab is an anti-programmed cell death protein-1 (PD-1) monoclonal antibody that binds PD-1, with the goal of restoring the antitumor activity of T cells. Zimberelimab has demonstrated high affinity, selectivity and potency in various tumor types.

Zimberelimab is being evaluated in the U.S. and globally as a foundational anti-PD-1 treatment option in multiple ongoing and planned early and late-stage clinical studies in combination with other immunotherapies, including investigational Fc-silent anti-TIGIT monoclonal antibody domvanalimab and A2a/A2b adenosine receptor antagonist etrumadenant.

Guangzhou Gloria Biosciences Co. Ltd., which holds commercialization rights for zimberelimab in greater China, has obtained approval for zimberelimab for the treatment of recurrent or metastatic cervical cancer and for relapsed or refractory classical Hodgkin’s lymphoma. Zimberelimab is not approved for any use in the U.S. or other regions outside of China. Gloria conducts its development and commercialization activities independent of Arcus and Gilead.

About Arcus Biosciences

Arcus Biosciences is a clinical-stage, global biopharmaceutical company developing differentiated molecules and combination medicines for people with cancer. In partnership with industry collaborators, patients and physicians around the world, Arcus is expediting the development of first- or best-in-class medicines against well-characterized biological targets and pathways and studying novel, biology-driven combinations that have the potential to help people with cancer live longer. Founded in 2015, the company has expedited the development of multiple investigational medicines into clinical studies, including new combination approaches that target TIGIT, PD-1, the adenosine axis (CD73 and dual A2a/A2b receptor), HIF-2a, CD39 and AXL. For more information about Arcus Biosciences’ clinical and preclinical programs, please visit www.arcusbio.com.

About Gilead Sciences

Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California.

SOURCE: Arcus Biosciences