Phase IbIII Study of Capivasertib with CDK46 Inhibitors and Fulvestrant versus CDK46 Inhibitors and Fulvestrant in Advanced Hormone Receptor-Positive, HER2-Negative Breast Cancer

What this Trial Is About

Researchers are evaluating the combination of capivasertib with CDK46 inhibitors and fulvestrant in adults with hormone receptor-positive and HER2-negative locally advanced or metastatic breast cancer. This Phase IbIII study aims to determine the safe dose for the combination treatment in the initial Phase Ib part and then compare its effectiveness and safety to standard treatment in the Phase III part in participants who have not received prior endocrine therapy in the advanced setting. In the Phase Ib portion, participants receive capivasertib combined with one of the CDK46 inhibitorspalbociclib, ribociclib, or abemacicliband fulvestrant to establish recommended doses. In the Phase III part, participants are randomly assigned to receive either capivasertib plus fulvestrant with a chosen CDK46 inhibitor palbociclib or ribociclib or fulvestrant with a CDK46 inhibitor alone. Treatments are given in 28-day cycles with specific dosing schedules for each drug, including oral doses of capivasertib and CDK46 inhibitors and injections of fulvestrant. Participants undergo screening and regular monitoring throughout the study, including assessments of treatment side effects, tumor progression, and blood samples for pharmacokinetics and biomarker analysis. The primary outcomes include dose-limiting toxicities and adverse events in Phase Ib and progression-free survival in Phase III, with follow-up lasting up to several years to evaluate overall survival, response rates, physical functioning, and quality of life.

Capivasertib + CDK4/6i + Fulvestrant for Advanced/Metastatic HR+/HER2- Breast Cancer (CAPItello-292)