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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/224502
Phase Ib study of xentuzumab and abemaciclib in patients with advanced solid tumors and in combination with endocrine therapy in patients with advanced breast cancer
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Background: This phase Ib trial assessed the insulin-like growth factor 1/2 neutralizing antibody, xentuzumab, plus abemaciclib +/- endocrine therapy (ET) in patients with advanced/metastatic solid tumors, including hormone receptor (HR)-positive breast cancer. Patients and methods: In part 1, patients with advanced solid tumors received escalating doses of xentuzumab + abemaciclib (cohort A). In part 2, dose-finding cohorts B-D had advanced/metastatic HR-positive, human epidermal growth factor receptor 2-negative breast cancer and received xentuzumab + abemaciclib plus letrozole, anastrozole, or fulvestrant. Part 3 included expansion cohorts assessing xentuzumab + abemaciclib plus fulvestrant in patients with HR-positive, human epidermal growth factor receptor 2-negative breast cancer with visceral (cohort D1) or non-visceral disease (cohort D2) who had progressed following ET, or non-visceral disease who had progressed following ET and a cyclin-dependent kinase inhibitor (cohort F). Primary endpoints were maximum tolerated dose (cohorts A-D), 18-month progression-free survival (cohort D1/D2) and disease control (cohort F). Comprehensive biomarker analyses were undertaken. Results: A total of 133 patients were treated. The maximum tolerated dose was xentuzumab 1000 mg once weekly plus abemaciclib 150 mg twice daily (cohorts A-D). The most common grade >= 3 adverse event was decreased neutrophil count. Cohorts B-D demonstrated response rates of >= 25%. The 18-month progression-free survival rate in cohorts D1/D2 was 41.4%/78.5%. The disease control rate in cohort F was 40.0%. Biomarker analysis indicated target engagement. Prognostic biomarkers included total serum insulin-like growth factor 1 concentrations, expression of CCND1, and MCL-1 mutations. Conclusions: Xentuzumab + abemaciclib + ETs demonstrated manageable tolerability and promising efficacy, especially in patients with breast cancer and non-visceral metastases.
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YEE, Douglas, et al. Phase Ib study of xentuzumab and abemaciclib in patients with advanced solid tumors and in combination with endocrine therapy in patients with advanced breast cancer. ESMO Open. 2025. Vol. 10, num. 11, pags. 105863. ISSN 2059-7029. [consulted: 9 of June of 2026]. Available at: https://hdl.handle.net/2445/224502