HCB101 (SIRPα–IgG4 Fc; CD47 checkpoint blocker) shows early monotherapy PRs and high combo disease control in gastric cancer

HCB101 is a CD47–SIRPα axis inhibitor (engineered SIRPα–IgG4 Fc fusion) designed to preserve pro-phagocytic macrophage activity while minimizing red-blood-cell binding/hematologic toxicity. In the first-in-human Phase 1 monotherapy dose escalation (HCB101-101; NCT05892718; weekly IV 0.08–36mg/kg), dosing reached 36mg/kg; as of 09JAN2026 there were 2 confirmed PRs (including HNSCC −42% at 5.12mg/kg lasting >44 weeks; plus a PR in marginal zone lymphoma) and 9 SD, with dose-proportional PK (t1/2 ≈2.9 days) and receptor occupancy plateau >99% at ≥8mg/kg. In the Phase 1b/2a combination platform (HCB101-201; NCT06771622), 2L gastric cancer treated with HCB101 + ramucirumab/paclitaxel reported 8 PR + 5 SD (mid-dose 5.12–8mg/kg: PR in 8/10; 100% disease control; tumor shrinkage up to −78.2%), which numerically exceeds historical ramucirumab/paclitaxel benchmarks from RAINBOW (ORR ~26.8%, mPFS ~4.4 months) but is based on small, early cohorts without mature time-to-event data; 1L HER2+ gastric cancer had 3 PR/4 and 1L TNBC had disease control in 6/6 (3 PR). Safety was described as manageable with reversible cytopenias and no unexpected immune-mediated toxicities; however, CD47/SIRPα class risk is hematologic toxicity, so discontinuation rates, transfusion needs, and detailed grade ≥3 cytopenia rates will matter as datasets mature.