Yee, DouglasIwata, HirojiLorusso, PatriciaOliveira, MafaldaGonçalves, AnthonyStradella, AgostinaVidal, MariaSablin, Marie PauleHardebeck, M. C.Fukuyama, YForman, NicolePuig, MartaLorence, Robert M.2025-11-282025-11-282025-10-252059-7029https://hdl.handle.net/2445/224502Background: 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.12 p.application/pdfengcc-by-nc-nd (c) Elsevier, 2025https://creativecommons.org/licenses/by-nc-nd/4.0/EtiquetatgeAnatomia humanaDiabetisLabelingHuman anatomyDiabetesinfo:eu-repo/semantics/article2025-11-26info:eu-repo/semantics/openAccess41135378