Phase 1 BSI-082 anti-SIRPα macrophage checkpoint antibody ± T-DXd HER2 ADC

This open-label Phase 1a/1b, two-part dose-escalation and dose-expansion study evaluates BSI-082 (a fully human anti–SIRPα monoclonal antibody that blocks the CD47–SIRPα “don’t eat me” signal to enhance macrophage-mediated phagocytosis and downstream T/NK anti-tumor immunity) as monotherapy and in combination with trastuzumab deruxtecan (T-DXd; Daiichi Sankyo/AstraZeneca’s HER2-directed antibody-drug conjugate delivering a deruxtecan topoisomerase I inhibitor payload). The Phase 1a portion escalates IV BSI-082 given every 21 days to define safety, pharmacokinetics, and a recommended dose; the Phase 1b combination evaluates BSI-082 with fixed-dose T-DXd and then expands in patients who have an FDA-approved indication for T-DXd. Eligible patients have locally advanced or metastatic solid tumors that are relapsed/refractory, progressed after available systemic therapy, or are ineligible for standard options. The key angle is pairing HER2-targeted ADC “eat me” biology with SIRPα blockade to counter adaptive anti-phagocytic signaling and potentially deepen responses beyond what ADC chemotherapy delivery alone achieves. Today’s care in these late-line solid tumors is histology- and biomarker-driven systemic therapy (chemo, targeted therapy when actionable alterations exist, and ADCs like T-DXd for appropriate HER2-expressing indications), with clinical trials commonly pursued after progression.