BeOne Medicines presents results from studies of BG-C9074, BG-68501 at ASCO

BeOne Medicines (ONC) announced new clinical data from its emerging breast cancer pipeline at the American Society of Clinical Oncology Annual Meeting in Chicago. Poster presentations feature preliminary results of the dose escalation studies of two investigational molecules: BG-C9074, a novel B7-H4-targeting antibody-drug conjugate in patients with advanced solid tumors, including breast cancer, and BG-68501, a cyclin-dependent kinase-2 inhibitor, in HR+/HER2- breast cancer patients with prior CDK4/6i exposure. BeOne presented initial results of the ongoing first-in-human, Phase 1a dose escalation study of BG-C9074 monotherapy in 78 patients with advanced solid tumors, of which more than a quarter were breast cancer patients. BG-C9074, an investigational topoisomerase I inhibitor ADC that targets the B7-H4 protein, which is broadly expressed in breast and gynecologic cancers, is designed with an innovative drug linker to deliver a potent cancer-killing drug directly to the cancer cells. With limited follow-up among the 56 efficacy-evaluable patients, preliminary clinical responses were observed at multiple dose levels across various tumor types without selection for B7-H4 expression in these heavily pretreated patients. Confirmed overall response rate was 16.1%, with 9 confirmed partial responses; unconfirmed ORR was 25.0%. Confirmed disease control rate was 73.2% and confirmed clinical benefit rate was 17.9%. Pharmacokinetics were observed to be approximately dose-proportional across dose levels. BG-C9074 showed a manageable safety and tolerability profile in patients with B7-H4 advanced solid tumors, including breast cancer. There were 5 dose-limiting toxicities reported among 3 dose levels, all related to treatment: grade 3 fatigue; grade 3 febrile neutropenia; and grade 4 platelet count decreased. The most common treatment-emergent adverse events were nausea, fatigue, and neutropenia. The most common grade greater than or equal to3 TEAEs were neutropenia and thrombocytopenia. There were no TEAEs leading to treatment discontinuation or death. These data support the continued development of BG-C9074 in patients with advanced solid tumors. Dose-escalation data from the first-in-human, Phase 1a study of a novel CDK2 inhibitor, BG-68501, were presented as a poster today. BG-68501 is designed to address elevated CDK2 activity as well as cyclin E1-driven upregulation, two key resistance mechanisms that often limit the effectiveness of CDK4/6 inhibitors in treating HR+/HER2- breast cancer. CDK inhibitors target checkpoint proteins that control cell division to stop the growth of cancer cells. A total of 57 enrolled patients with advanced solid tumors, including 19 patients with HR+/HER2- metastatic breast cancer, received BG-68501 as monotherapy or in combination with fulvestrant in escalating dose cohorts. Of the 37 efficacy-evaluable patients, unconfirmed overall response rate was 5.4%. Two extensively pretreated patients experienced unconfirmed partial response, 15 patients had stable disease, 15 patients had progressive disease, and 5 patients were not evaluable/not assessed. Of the 2 patients with PR, both were breast cancer patients, and one was ongoing with treatment at the time of data cutoff, while the other had discontinued treatment. Unconfirmed clinical benefit rate was 8.1% and unconfirmed disease control rate was 45.9%. BG-68501 demonstrated a linear PK profile consistent with preclinical data and signs of pharmacodynamic responses. BG-68501 demonstrated a manageable safety and tolerability profile, with no DLTs observed to date during dose escalation. The most common TEAEs were vomiting, nausea, and fatigue, and TEAEs leading to treatment discontinuation occurred in 4 patients across all dose levels. There were no TEAEs leading to death. The data support continued development of BG-68501 as a next-line option for tumors with CDK2 dependency.