BG-C9074 B7-H4–targeting topo I ADC shows 28.1% confirmed ORR (34.5% in ovarian; 31.3% in TNBC) in heavily pretreated solid tumors

BG-C9074 is a B7-H4–directed antibody-drug conjugate delivering a topoisomerase I inhibitor payload; in the ongoing first-in-human Phase 1 BG-C9074-101 dose-escalation/safety-expansion study (NCT06233942), patients with advanced solid tumors received IV BG-C9074 Q3W at 1–9mg/kg irrespective of B7-H4 expression (monotherapy; n=123 treated; median 4 prior lines). Among 114 efficacy-evaluable patients, confirmed ORR was 28.1% (2 CRs, 30 PRs), including 34.5% in ovarian cancer (n=55), 31.3% in TNBC (n=16), and 17.9% in HR+/HER2− breast cancer (n=28), with responses reported across B7-H4 expression levels (no consistent expression–response relationship); median follow-up was 6.0 months. TRAEs occurred in 91.9% with grade ≥3 in 30.1%; key toxicities were nausea (53.7%; grade ≥3 4.1%) and neutropenia/neutrophil decrease (44.7%; grade ≥3 18.7%); DLTs included thrombocytopenia, febrile neutropenia/neutropenic infection, fatigue, nausea, and 1 unexplained death at 9mg/kg—broadly in-family for topo I ADCs, and the observed OC ORR (34.5%) is above typical single-agent non-platinum chemo activity in recurrent/platinum-resistant OC (~12%–14% ORR), while the TNBC ORR (31.3%) lands in the same ballpark as sacituzumab govitecan’s ~35% ORR in later-line mTNBC (but cross-trial comparisons are shaky given small TNBC n and mixed lines of therapy).