This Phase Ib/III study (CAPItello-292) aims to evaluate the efficacy, safety and the degree of added benefit of capivasertib combined with CDK4/6i (palbociclib, ribociclib or abemaciclib) and fulvestrant in participants with locally advanced (inoperable) or metastatic HR+/HER2- breast cancer. Although the dosing regimens of capivasertib + fulvestrant and of CDK4/6i + fulvestrant are established separately, the dose and schedule for the triplet combinations (capivasertib + CDK4/6i + fulvestrant) need to be confirmed. Therefore, the initial dose finding Phase Ib part of the study will determine the recommended Phase III doses (RP3D) of the triplet combinations. The efficacy and safety of capivasertib plus palbociclib and fulvestrant will be compared to placebo plus palbociclib and fulvestrant in the randomised, double-blind Phase III part. In addition, if safe and tolerable doses are identified for either of the triplet combination with ribociclib or abemaciclib and AstraZeneca decides to study these combinations further, the Phase III part of the protocol will be amended to include these additional CDK4/6i treatment options.
A Phase Ib/III Randomised Study of Capivasertib plus CDK4/6i and Fulvestrant versus Placebo plus CDK4/6i and Fulvestrant in Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced, Unresectable or Metastatic Breast Cancer (CAPItello-292)