The objective of the study was to evaluate the safety, preliminary antitumor activity, and pharmacokinetics of BG-C9074, an investigational topoisomerase I inhibitor antibody-drug conjugate (ADC) that targets B7-H4, as monotherapy in patients with advanced solid tumors.
This was a first-in-human, multicenter Phase 1 study that included monotherapy dose escalation and safety expansion cohorts. Eligible patients had progressed after prior therapies and were enrolled irrespective of B7-H4 expression status. Endpoints included safety, preliminary antitumor activity assessed using RECIST version 1.1, and pharmacokinetics.
As of December 29, 2025, 123 patients with advanced solid tumors received BG-C9074 monotherapy in Phase 1a (ovarian, n=62; HR+/HER2- breast cancer, n=28; triple negative breast cancer, n=18; cholangiocarcinoma, n=11; endometrial, n=3; squamous non-small cell lung cancer, n=1).
Dose-limiting toxicities were reported in 8 patients across dose levels and included thrombocytopenia, febrile neutropenia, neutropenic infection, fatigue, nausea, and one unexplained death. Treatment-related adverse events occurred in 91.9% of patients, with Grade ≥3 events reported in 30.1%. The most common treatment-related adverse events were nausea (53.7%; Grade ≥3, 4.1%), neutropenia or decreased neutrophil count (44.7%; Grade ≥3, 18.7%), and fatigue (37.4%; Grade ≥3, 2.4%).
Among 114 efficacy-evaluable patients, the confirmed objective response rate was 28.1%, with 2 complete responses and 30 partial responses reported. Responses were observed across doses and levels of B7-H4 expression, without consistent association of response with B7-H4 expression across tumor types. Median (range) study follow-up was 6.0 (0.3-17.7) months.
Pharmacokinetic analyses showed that ADC and free payload concentrations decreased in a biexponential manner with a half-life of ~7 days for ADC. Exposure for ADC and free payload increased approximately dose proportionally.
