Neoadjuvant Anti-PD-L1 Antibody Therapy with Danburstotug (IMC-001) in Resectable Gastric, Esophageal, and Hepatocellular Carcinoma: The NeoChance Phase II study

Background: Neoadjuvant immunotherapy has the potential to improve long-term outcomes in resectable cancers by activating antitumor immunity before surgery. We evaluated the efficacy, safety, and immunomodulatory activity of danburstotug (IMC-001), an anti–PD-L1 antibody, in resectable gastric cancer (GC), esophageal squamous cell carcinoma (ESCC), and hepatocellular carcinoma (HCC). Methods: In this single-center, open-label, multi-cohort, phase II trial (NCT04196465), patients with resectable GC, ESCC, or HCC received two cycles of danburstotug (20 mg/kg every 2 weeks) before surgery. The primary endpoint was major pathologic response (MPR, <10% viable tumor). Key secondary endpoints included safety, radiologic/metabolic response, survival outcomes, and immune profiling using multiplex immunofluorescence, AI-based immune phenotyping (Lunit SCOPE IO), and bulk RNA sequencing. Findings: Fifty patients were enrolled; 48 comprised the per-protocol population (16 per cohort). MPR was achieved in 2/48 patients (4.2%)—one ESCC and one HCC (6.3% per cohort). Pathologic tumor regression to ≤50% viable tumor was observed in 11/48 (22.9%; GC 25.0%, ESCC 31.3%, HCC 12.5%). Among evaluable patients, partial responses were observed radiographically in 17.6% and metabolically in 23.3%. Treatment was well tolerated, with grade ≥3 treatment-related adverse events in 6.0% and no grade 4–5 events; one treatment-related surgical delay occurred. All patients underwent surgery with R0 resection. Immune profiling revealed robust post-treatment infiltration of effector cells in GC and ESCC, with regulatory/myeloid expansion largely confined to ESCC. Transcriptomics analysis showed cancer type–specific programs: ESCC responders lacked baseline inflammatory signatures enriched in non-responders, whereas GC (and post-treatment HCC) responses aligned with productive inflammatory or interferon-driven states. Interpretation: Neoadjuvant danburstotug was safe and induced both immunologic remodeling and measurable tumor regression across GC, ESCC, and HCC, in a predominantly PD-L1–negative, microsatellite-stable tumors.