Irrespective of PD-L1 expression, patients treated with domvanalimab, zimberelimab, and chemotherapy in arm A1 of the phase 2 EDGE-Gastric study demonstrated promising overall response rate and 6-month progression-free survival results.
The combination of domvanalimab with zimberelimab and chemotherapy generated an encouraging overall response rate (ORR) and 6-month progression-free survival (PFS) rate among patients with locally advanced unresectable or metastatic gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma, according to findings from cohort A1 of the ongoing phase 2 EDGE-Gastric study (NCT05329766).
These findings were presented by Yelena Y. Janjigian, MD, during the ASCO Plenary Series: November 2023 Session. As of the data cutoff date of September 4, 2023, a total of 41 patients were enrolled and treated with a median follow-up of 8.1 months, and 24 patients (59%) remained on study treatment at this time. The median time on treatment was 33 weeks (range, <1-53 weeks).
“The addition of domvanalimab and zimberelimab to FOLFOX shows encouraging overall response rate and 6-month PFS in the firstline for patients with advanced gastroesophageal adenocarcinoma, irrespective of PD-L1 expression,” said Janjigian, a medical oncologist and chief of the Gastrointestinal Oncology Service at Memorial Sloan Kettering Cancer Center, during the presentation.
With the combination of domvanalimab, zimberelimab, and chemotherapy, patients with PD-L1-high tumors had an ORR of 80% (95% CI, 52-96), and patients with PD-L1-low tumors had an ORR of 46% (95% CI, 26-67). For patients overall, the ORR was 59% (95% CI, 42-74), and 2 confirmed complete responses were observed.
Looking at PFS at 6 months, rates were 93% for patients with PD-L1-high tumors (95% CI, 81-100), 68% for patients with PD-L1-low tumors (95% CI, 48-88), and 77% for patients overall (95% CI, 64-90). Additionally, the median PFS was not reached. Mature PFS data are anticipated to be released in the second half of 2024.
For safety, the domvanalimab-containing regimen showed a similar safety profile to what has been previously seen for anti-PD-1 plus chemotherapy in this setting. Domvanalimab plus zimberelimab and chemotherapy was also well-tolerated, and the most common adverse events (AEs) included neutropenia (59%), nausea (54%), anemia (27%) and fatigue (27%).
Twenty percent of patients had an infusion-related reaction; however, most (17%) were related to chemotherapy. No serious immune-mediated AEs were experienced by any patient in the study, and no treatment-emergent adverse events (TEAEs) resulted in death.
“There were no new safety signals and no new treatment-related deaths...AE incidence was similar to prior experience with anti-PD-1 plus FOLFOX,” explained Janjigian.
These data from cohort A1 of this phase 3 study add to the growing body of evidence that domvanalimab has encouraging and differentiated safety and tolerability profiles.
EDGE-Gastric is an ongoing, multi-arm, global, phase 2 study evaluating the safety and efficacy of domvanalimab, an Fc-silent anti-TIGIT antibody, plus zimberelimab, an anti-PD-1 antibody, with and without chemotherapy for the treatment of patients with locally advanced unresectable or metastatic gastric, GEJ, or esophageal adenocarcinoma.2 Chemotherapy consists of oxaliplatin, leucovorin, and fluorouracil (FOLFOX).
Patients received 1600 mg of domvanalimab intravenously (IV) every 4 weeks (Q4W) plus 480 mg of zimberelimab IV Q4W, and chemotherapy, which consisted of oxaliplatin 85 mg/m2 IV, leucovorin 400 mg/m2 IV, fluorouracil 400 mg/m2 IV bolus and 2400 mg/m2 continuous 46-48-hour IV infusion every 2 weeks.
Enrollment in the study was open to patients aged 18 years and older with histologically confirmed diagnosis of locally advanced unresectable or metastatic gastric, GEJ, or esophageal adenocarcinoma who had a life expectancy ≥3 months as assessed by the investigator, an ECOG performance status of 0-1, at least 1 measurable target lesion per RECIST v1.1., and adequate organ and marrow function. Patients must also have provided an archival tumor sample that is representative of the cancer under investigation and suitable for central PD-L1 testing.
Cohort A1 evaluated the combination of domvanalimab plus zimberelimab and chemotherapy given as an initial treatment in approximately 40 patients.
The mean age of patients was 61 years (range, 30-82), 24 patients were male, and 22 patients were from the United States or France, while 19 were from Korea. Twenty-four (59%) patients had an ECOG performance status of 1, and 24 (59%) patients had MSS/MSI-low status.
Primary end points of the study are the incidence and severity of AEs, serious AEs, any clinically meaningful trends in safety parameters, and ORR. Secondary end points include ORR, overall survival, PFS, disease control, duration of response, and pharmacokinetics.
In addition to EDGE-Gastric, 3 additional phase 3 registrational studies are ongoing and assessing domvanalimab-containing regimens in lung cancer, including STAR-121 (NCT05502237), ARC-10 (NCT04736173), and PACIFIC-8 (NCT05211895). These preliminary data also support the ongoing STAR-221 trial (NCT05568095) in unresectable or metastatic upper GI cancers.