SIRPα blocker BI 765063 + PD-1 (ezabenlimab) + cetuximab drives 47% ORR in 2L SIRPα-V1 HNSCC

In an open-label Phase Ib trial (NCT05249426), 17 eligible patients with recurrent/metastatic HNSCC after one prior systemic therapy—all homozygous for the SIRPα V1 allele—received BI 765063, a signal regulatory protein α (SIRPα) antagonist, (24 mg/kg Q3W) plus PD-1 inhibitor ezabenlimab 240 mg Q3W and cetuximab, an anti-EGFR monoclonal antibody. Confirmed ORR reached 47% (3 CR, 5 PR) with an 88% DCR and mPFS of 7.6 mo. All patients experienced TEAEs; acneiform dermatitis (53%, none ≥G3) and anemia (35%, 24% ≥G3) were most common, while grade 3 drug-related events were isolated and no grade 4/5 TRAEs occurred.