Neoadjuvant Danburstotug (IMC-001) therapy in gastric, esophageal, and hepatocellular carcinoma: the NeoChance phase II study.

Neoadjuvant immunotherapy may improve long-term outcomes by activating antitumor immunity before surgery. We evaluated danburstotug (IMC-001), an anti-PD-L1 antibody, in resectable gastric cancer (GC), esophageal squamous cell carcinoma (ESCC), and hepatocellular carcinoma (HCC). In this phase II trial, patients 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 translational immune profiling. Forty-eight patients were evaluable (16 per cohort). The study did not meet its pre-specified primary endpoint, with MPR achieved in 2/48 patients (4.2%)-one ESCC and one HCC (6.3% per cohort). However, pathologic tumor regression to ≤50% viable tumor was observed in 11/48 patients (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; two surgical delays were observed, of which one was treatment-related. All patients underwent surgery with R0 resection. Immune profiling revealed cancer type-specific immune-remodeling. Neoadjuvant danburstotug was safe, did not compromise surgical outcomes, and provided exploratory insights into treatment-induced immune microenvironment remodeling. ClinicalTrials.gov ID: NCT04196465, date of registration: August 28, 2019.