%0 Journal Article
%T Phase Ib Trial of Xentuzumab Combined with Abemaciclib in Patients with Advanced Solid Tumors, Including Its Use Alongside Endocrine Therapy in Advanced Breast Cancer
%A Katya Ivanova Sokolova
%A Elena Vladimirovna Petrova
%A Jan Marek Kowalski
%A Adam Pawel Wisniewski
%J Archive of International Journal of Cancer and Allied Science
%@ 3108-4834
%D 2022
%V 2
%N 2
%R 10.51847/m2jHDVGQlR
%P 89-102
%X 
This phase Ib study evaluated the IGF-1/IGF-2-neutralizing antibody xentuzumab combined with abemaciclib, with or without endocrine therapy (ET), in patients with advanced or metastatic solid tumors, particularly hormone receptor (HR)-positive, HER2-negative breast cancer. In the initial dose-escalation phase (cohort A), patients with advanced solid tumors received increasing doses of xentuzumab combined with abemaciclib. Subsequent dose-finding phases (cohorts B–D) enrolled patients with advanced/metastatic HR-positive, HER2-negative breast cancer, who received xentuzumab plus abemaciclib in combination with letrozole, anastrozole, or fulvestrant. Expansion phases evaluated xentuzumab plus abemaciclib and fulvestrant in patients with HR-positive, HER2-negative breast cancer who had progressed on prior ET, focusing on those with visceral metastases (cohort D1), non-visceral disease (cohort D2), or non-visceral disease after prior ET and CDK inhibitor therapy (cohort F). Primary outcomes included maximum tolerated dose (MTD) for cohorts A–D, 18-month progression-free survival (PFS) rate for cohorts D1/D2, and disease control rate for cohort F. Extensive biomarker evaluations were also performed.

Overall, 133 patients received treatment. The MTD was established as xentuzumab 1000 mg weekly plus abemaciclib 150 mg twice daily (cohorts A–D). The most frequent grade ≥3 adverse event was neutropenia. Response rates in cohorts B–D were at least 25%. The 18-month PFS rates were 41.4% in cohort D1 and 78.5% in cohort D2. The disease control rate in cohort F reached 40.0%. Biomarker assessments confirmed target inhibition, with potential prognostic indicators including baseline serum IGF-1 levels, CCND1 expression, and MCL-1 mutations. The combination of xentuzumab with abemaciclib and ET showed acceptable safety and encouraging clinical activity, particularly in breast cancer patients with non-visceral metastases.

%U https://smerpub.com/article/phase-ib-trial-of-xentuzumab-combined-with-abemaciclib-in-patients-with-advanced-solid-tumors-inclu-uxuouc6bii4alwv