Domvanalimab combined with zimberelimab as first-line treatment in patients with PD-L1–high, advanced non-small cell lung cancer: Results from the randomized phase 2 ARC-10 study, Part1
Mené sur 98 patients atteints d'un cancer du poumon non à petites cellules surexprimant PD-L1 et de stade avancé (durée médiane de suivi : 24,5 mois), cet essai multicentrique de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité d'un traitement de première ligne combinant domvanalimab (un anti-TIGIT) et zimbérélimab (un anti-PD-1)
Introduction: TIGIT and PD-1 trigger distinct but interconnected immunosuppressive pathways. We investigated first-line domvanalimab (Fc-silent anti-TIGIT) plus zimberelimab (anti–PD-1) in PD-L1–high (≥50%), stage IIIB–IV NSCLC.
Materials and Methods: This phase 2, multicenter, randomized, open-label study (ARC-10, Part 1) randomized (2:2:1) patients to intravenous domvanalimab 15 mg/kg plus zimberelimab 360 mg (DZ), zimberelimab 360 mg (Z), or platinum-doublet chemotherapy every 3 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), confirmed objective response rate (ORR), and safety.
Results: Of 98 randomized patients, 95 received treatment (DZ, n = 38; Z, n = 40; chemotherapy, n = 17). As of May 17, 2024, median follow-up was 24.5 months; 22patients remained on first-line treatment (DZ, n = 11; Z, n = 10; chemotherapy, n = 1). Median (95% CI) PFS was 11.5 (4.0–26.2) months for DZ, 6.2 (2.5–12.3) months for Z, and 9.6 (2.6–16.4) months for chemotherapy. Median (95% CI) OS was not reached (13.7-not evaluable [NE]) for DZ, 24.4(7.8-NE) months for Z, and 11.9(2.7-NE) months for chemotherapy. DZ vs Z hazard ratio (95% CI) was 0.69 (0.40–1.18) for PFS and 0.64 (0.32–1.25) for OS. ORR (95% CI) was 44.7% (28.6–61.7) for DZ, 35.0% (20.6–51.7) for Z, and 35.3% (14.2–61.7) for chemotherapy. Grade ≥ 3 treatment-related AEs were lower for DZ (21.1%) and Z (15.0%) vs chemotherapy (47.1%). Immune-mediated AEs were similar between DZ (23.7%) and Z (20.0%). Infusion-related reactions were low (0%-7.9% across arms).
Conclusions: Adding Fc-silent anti-TIGIT (domvanalimab) to anti–PD-1 (zimberelimab) led to encouraging efficacy and showed no new safety concerns in patients with previously untreated stage IIIB–IV NSCLC.
Lung Cancer , résumé, 2026