On November 6, 2023 Gilead Sciences, Inc. (Nasdaq: GILD) and Arcus Biosciences, Inc. (NYSE: RCUS) reported that domvanalimab plus zimberelimab and chemotherapy showed encouraging overall response rate (ORR) and six-month progression-free survival (PFS) rate results in a preliminary analysis from Arm A1 of the EDGE-Gastric study (Press release, Gilead Sciences, NOV 6, 2023, View Source [SID1234637079]). This ongoing Phase 2, multi-arm, global study is evaluating the safety and efficacy of various combinations of the Fc-silent anti-TIGIT antibody domvanalimab plus the anti-PD-1 antibody zimberelimab and chemotherapy in patients with locally advanced unresectable or metastatic gastric, gastroesophageal junction or esophageal adenocarcinoma. These results will be presented tomorrow during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Monthly Plenary Series, a virtual forum for presentation and discussion of the latest cancer research.

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"The preliminary data from the EDGE-Gastric study underscore the potential role of dual anti-TIGIT and anti-PD-1-containing regimen in the treatment of gastroesophageal cancer where front-line chemotherapy with anti-PD-1 blockade is currently the standard," said Yelena Y. Janjigian, M.D., Chief Attending Physician of the Gastrointestinal Medical Oncology Service, Memorial Sloan Kettering Cancer Center, and a principal investigator for the EDGE-Gastric study. "These early data are encouraging and indicate the potential for the anti-TIGIT, domvanalimab-based therapy to improve upon anti-PD-1 and chemotherapy in this setting, with a similar safety profile to anti-PD-1 and chemotherapy."

At data cutoff (September 4, 2023), 41 patients were enrolled and treated with a median follow-up of 8.1 months; 24 patients (59%) remained on study treatment at time of data cutoff. Median time on treatment was 33 weeks (range: <1 to 53 weeks).

The domvanalimab-containing regimen showed an objective response rate (ORR) of 80% in patients with PD-L1-high tumors (tumor activity positivity (TAP) ≥5%), 46% in patients with PD-L1-low tumors (TAP <5%) and 59% for patients overall. There were two confirmed complete responses. Six-month landmark PFS rate was 93% for patients with PD-L1-high tumors (TAP ≥5%), 68% for patients with PD-L1-low tumors (TAP <5%) and 77% for patients overall. Median PFS was not reached and mature PFS data are expected in the second half of next year.

The efficacy results including ORR and six-month PFS rates are summarized in the table below:

PD-L1-high*

(TAP ≥5%)

N=15

n (%)

PD-L1-low* (TAP <5%)

N=24

n (%)

Overall

N=41

n (%)

ORR (95% CI)

80%

(52,96)

46%

(26,67)

59%

(42,74)

Confirmed ORR (95% CI)

73%

(45,92)

46%

(26,67)

56%

(40,72)

6-month PFS Rate (95% CI)

93%

(81,100)

68%

(48,88)

77%

(64,90)

*Tumor samples from 2 patients were not available for central PD-L1 testing

CI: confidence interval

The domvanalimab-containing regimen was well tolerated, with a similar safety profile to what has been reported for anti-PD-1 plus chemotherapy in this setting. The most common adverse events (AEs) were neutropenia (59%), nausea (54%), anemia (27%) and fatigue (27%). Infusion-related reactions were observed in 20% and the majority (17%) were related to chemotherapy. No patients experienced serious immune-mediated AEs, and there were no treatment-emergent adverse events (TEAEs) resulting in death.

These data add to the growing body of evidence that domvanalimab, an Fc-silent anti-TIGIT antibody, has a differentiated safety and tolerability profile relative to published data from studies with Fc-enabled anti-TIGIT antibodies.

The preliminary data from Arm A1 of the Phase 2 EDGE-Gastric study support the ongoing Phase 3 study, STAR-221, in unresectable or metastatic upper GI cancers. The companies have three additional ongoing Phase 3 registrational studies of domvanalimab-containing regimens in lung cancer, including STAR-121, ARC-10 and PACIFIC-8.

Domvanalimab and zimberelimab 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 gastrointestinal and lung cancers have not been established.

About the EDGE-Gastric Study

The ongoing, multi-arm, global 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 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 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.