BG-C9074 is a B7-H4-targeting antibody-drug conjugate (ADC) composed of a humanized anti-B7-H4 IgG1 antibody conjugated via a cleavable linker to a topoisomerase I inhibitor (TOP1i) payload with a drug-to-antibody ratio (DAR) ~6.1
In a first-in-human phase 1a/1b study, BG-C9074 demonstrated a generally manageable safety profile, dose-proportional pharmacokinetics, and preliminary antitumor activity across multiple solid tumor types, supporting continued clinical development as monotherapy and in combination with tislelizumab.1
BG-C9074 is designed to deliver clinically meaningful exposure of conjugated payload with limited systemic exposure.1 In a first-in-human phase 1a/1b study, confirmed partial responses and durable disease control were observed across multiple tumor types without preselection for B7-H4 expression in a heavily pretreated population (median 4 prior lines of therapy).1
These findings validate the B7-H4 ADC strategy and support further dose optimization and expansion, including combination with PD-1 blockade, which is under evaluation (NCT06233942).
Safety and efficacy have not been established for investigational products and/or uses. The clinical relevance of nonclinical data has not been established.
ADC, antibody-drug conjugate; B7-H4, B7 family homolog 4 (or VTCN1, V-set domain-containing T-cell activation inhibitor 1); DAR, drug-to-antibody ratio; gyn, gynecologic; IgG1, immunoglobulin G1; TOP1i, topoisomerase 1 inhibitor; PD-1, programmed cell death protein 1.
B7-H4 is a transmembrane glycoprotein in the B7 immune regulatory family with limited expression in normal adult tissues and frequent upregulation in solid tumors, including cholangiocarcinoma, ovarian cancer, breast cancer, endometrial cancer, and squamous NSCLC. High B7-H4 expression has been associated with poor prognosis and immune-suppressive tumor phenotypes, supporting its role as a tumor-associated antigen.1-3
Importantly for ADC development, B7-H4 is cell-surface accessible and internalized, enabling effective delivery of cytotoxic payloads to tumor cells while minimizing normal-tissue exposure.1,4
BG-C9074 binds B7-H4 on tumor cells, undergoes internalization, and releases its TOP1i payload, leading to DNA damage and tumor cell death.4 Consistent with TOP1 inhibition, preliminary antitumor activity was observed across tumor types with varying B7-H4 expression, supporting both direct target-mediated killing and a bystander effect.1
ADC, antibody-drug conjugate; B7-H4, B7 family homolog 4 (or VTCN1, V-set domain-containing T-cell activation inhibitor 1); TOP1, topoisomerase 1; TOP1i, topoisomerase 1 inhibitor.
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