EDGE-Gastric Arm A1: Phase 2 study of domvanalimab (D), zimberelimab (Z), and FOLFOX in first-line (1L) advanced gastroesophageal (GE) cancer

Background: Adding programmed cell death protein 1 (PD-1) inhibitors to chemotherapy confers a survival advantage in 1L GE cancers, yet long-term outcomes remain poor. Dual PD-1 and anti-T-cell immunoglobulin and ITM domain (TIGIT) blockade increases tumor specific CD8+T cells, resulting in potent antitumor activity.

Aim of the Study: The ongoing, multi-arm, global EDGE-Gastric trial (NCT05329766) is evaluating the safety and efficacy of various combinations of the anti-TIGIT Fc-silent monoclonal antibody (mAb) domvanalimab (D) and the anti-PD-1 mAb zimberelimab (Z) in patients (pts) with locally advanced unresectable or metastatic gastric (G)/gastroesophageal junction (GEJ)/esophageal (E) adenocarcinoma. Arm A1 is fully enrolled and results from this 1L arm are presented here.

Methods: Pts received D 1600 mg intravenously (IV) every 4 weeks (Q4W)+Z 480 mg 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) Q2W. Primary endpoints were safety and objective response rate (ORR) per RECIST 1.1. Secondary endpoints included ORR by PD-L1 status and PFS.

Results: As of data cutoff (12Mar2024), 41 pts were enrolled. There was an even distribution of pts from Asia vs. rest of world; 63% had gastric cancer. Median (m) time on treatment was 11.4 months, 13 pts (32%) continue on therapy. Confirmed ORR was 59% (95% CI 42, 74) and mPFS was 12.9 months (9.8, 13.8). Outcomes by PD-L1 status are in [Table 1]. Most common treatment-emergent adverse events (TEAE) were neutropenia (61%), nausea (59%), and anemia (29%). Infusion related reactions (investigator assessed) were observed in 20% (n=8); n=2 related to D/Z. Grade≥3 TEAEs occurred in 73% of pts; 59% and 15% related to FOLFOX and D/Z, respectively. Serious TEAEs occurred in 37% of pts: 5% related to FOLFOX and none to D/Z. TEAEs leading to FOLFOX discontinuation occurred in 26 pts (63%), and D/Z discontinuation in 4 pts (10%). There were no treatment related deaths.

Table 1 

	Overall (n=41)	PD-L1 High (TAP≥5%) (n=16)	PD-L1 Low (TAP<5%) (n=24)
Confirmed ORR,% (95% CI)	59 (42, 74)	69 (41, 89)	50 (29, 71)
Median PFS, months (95% CI)	12.9 (9.8, 13.8)	13.8 (11.3, NE)	11.3 (5.5, 13.8)
12-mo PFS Rate,% (95% CI)	58 (42, 74)	69 (46, 92)	47 (25, 69)

Tumor samples from 40 pts were available for central PD-L1 testing; NE: not estimable; PFS: progression free survival; TAP: Tumor Area Positivity.

Conclusions: Addition of DZ to FOLFOX showed encouraging ORR and mPFS, particularly in pts with PD-L1-high tumors. The regimen was well tolerated, with a similar AE profile to anti-PD-1+FOLFOX.

 

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Publication History

Article published online:
04 September 2025