BeOne Medicines Ltd. announced promising preliminary clinical data for two investigational breast cancer therapies at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. The global oncology company presented first-in-human results for BG-C9074, a novel B7-H4-targeting antibody-drug conjugate (ADC), and BG-68501, a cyclin-dependent kinase-2 (CDK2) inhibitor, both designed to address critical unmet needs in breast cancer treatment.
"Presenting the first clinical data for two novel breast cancer candidates at ASCO 2025 marks a pivotal moment for BeOne," said Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeOne. "These early results highlight the strong potential of our B7-H4-targeting ADC and CDK2 inhibitor to address critical gaps in breast cancer treatment."
BG-C9074 Shows Encouraging Response Rates in Advanced Solid Tumors
The ongoing Phase 1a dose escalation study of BG-C9074 enrolled 78 patients with advanced solid tumors, with more than a quarter being breast cancer patients. BG-C9074 is an investigational topoisomerase I inhibitor ADC that targets the B7-H4 protein, which is broadly expressed in breast and gynecologic cancers. The therapy is designed with an innovative drug linker to deliver a potent cancer-killing drug directly to cancer cells.
Among 56 efficacy-evaluable patients, the confirmed overall response rate (ORR) reached 16.1% (9/56; 95% CI: 7.6%–28.3%), with 9 confirmed partial responses. The unconfirmed ORR was 25.0% (14/56; 14.4%-38.4%). The confirmed disease control rate (DCR) was 73.2% (59.7%-84.2%) and confirmed clinical benefit rate (CBR) was 17.9% (8.9%-30.4%). Notably, these responses were observed across multiple dose levels and various tumor types without selection for B7-H4 expression in heavily pretreated patients.
The safety profile proved manageable, with 5 dose-limiting toxicities (DLTs) reported among 3 dose levels, all treatment-related: grade 3 fatigue (n=1), grade 3 febrile neutropenia (n=2), and grade 4 platelet count decreased (n=2). The most common treatment-emergent adverse events (TEAEs) were nausea, fatigue, and neutropenia, while the most common grade ≥3 TEAEs were neutropenia and thrombocytopenia. Importantly, no TEAEs led to treatment discontinuation or death.
CDK2 Inhibitor Targets Resistance Mechanisms
The Phase 1a study of BG-68501 enrolled 57 patients with advanced solid tumors, including 19 patients with HR+/HER2- metastatic breast cancer who had all received prior CDK4/6 inhibitor therapy. BG-68501 is specifically designed to address elevated CDK2 activity and cyclin E1-driven upregulation, two key resistance mechanisms that often limit the effectiveness of CDK4/6 inhibitors in treating HR+/HER2- breast cancer.
Among 37 efficacy-evaluable patients receiving monotherapy, the unconfirmed overall response rate was 5.4% (2/37; 95% CI: 0.7%–18.2%). Two extensively pretreated patients experienced unconfirmed partial responses, with 15 patients (40.5%) achieving stable disease and 15 patients (40.5%) experiencing progressive disease. Both patients with partial responses were breast cancer patients, with one continuing treatment at data cutoff. The unconfirmed clinical benefit rate was 8.1% (3/37; 95% CI: 1.7%-21.9%) and disease control rate was 45.9% (17/37; 95% CI: 29.5%-63.1%).
BG-68501 demonstrated a manageable safety profile with no DLTs observed during dose escalation. The most common TEAEs were vomiting, nausea, and fatigue. Treatment discontinuation due to TEAEs occurred in 4 patients (7%) across all dose levels, with no treatment-related deaths reported.
Expanding Breast Cancer Pipeline
BeOne is advancing a robust portfolio of investigational medicines for breast cancer, including three molecules in clinical development: two CDK inhibitors (BGB-43395, a CDK4 inhibitor, and BG-68501) and the ADC BG-C9074. The company also plans to evaluate BCL2 inhibition in breast cancer with next-generation BCL2 inhibitor BGB-21447, expected to begin clinical testing in solid tumor indications soon.
The clinical development occurs against the backdrop of significant global disease burden. Breast cancer accounts for close to one in four cancer cases and one in six cancer deaths in women worldwide. More than 2.3 million patients were diagnosed with breast cancer in 2022, with over 666,000 deaths reported globally. Approximately two-thirds of breast cancer cases are the HR+/HER2- subtype, representing the patient population targeted by BG-68501.
Both studies support continued development of these investigational therapies, with BG-C9074 advancing in patients with advanced solid tumors (NCT06233942) and BG-68501 being evaluated as a next-line option for tumors with CDK2 dependency (NCT06257264).
