243MO SHR-1701 Plus CAPOX for advanced gastric or gastroesophageal junction adenocarcinoma with high-risk features: Results from a phase III study

Methods: HCB101-101 (NCT05892718) is a first-in-human phase 1 monotherapy dose-escalation study evaluating weekly IV dosing up to 30 mg/kg.HCB101-201 (NCT06771622) is a phase 1b/2a multi-cohort trial assessing HCB101 in combination with standard-of-care (SOC) agents across solid tumor types, including gastric cancer (GC), triple-negative breast cancer (TNBC), head and neck squamous cell carcinoma (HNSCC), etc.Primary endpoints are safety, tolerability, and determination of the recommended phase 2 dose; secondary and exploratory endpoints include pharmacokinetic (PK), pharmacodynamics (PD), efficacy, and biomarkers.Results: Among 55 participants treated in HCB101-101, HCB101 was generally well tolerated.Cytopenias and infusion-related reactions were manageable.Confirmed partial responses (PRs) included HNSCC (-42% regression at 5.12 mg/kg) and marginal zone lymphoma (-89.6% regression at 16 weeks).PK was dose-proportional (T 1/2 2.9 days) with receptor occupancy plateauing at >90% by 8 mg/kg, confirming biologically active exposures.In HCB101-201, combinations showed striking efficacy: in 2L GC, HCB101 with ramucirumab and paclitaxel achieved 100% ORR (6/ 6) at 5.12-8.0mg/kg, with regressions up to -78.2%, far exceeding historical benchmarks (28%).In 1L TNBC, a durable PR with -73% regression was observed.Safety across combination cohorts was consistent with known SOC toxicities and manageable with standard interventions, with no new immune-related or off-target safety signals attributable to HCB101.Conclusions: HCB101 demonstrates a favorable safety profile, durable monotherapy activity in HNSCC and NHL, and striking combination efficacy in GC and TNBC.These data establish HCB101 as a differentiated SIRP-CD47 therapy with the potential to overcome class limitations and support registrational development across multiple tumor types.