A Phase Ib/III Open-label Randomised Study of Capivasertib plus CDK4/6 Inhibitors and Fulvestrant versus CDK4/6 Inhibitors and Fulvestrant in Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced Unresectable or Metastatic Breast Cancer (CAPItello-292)

Brief description of study

This is a Phase Ib/III, multicentre study of capivasertib plus CDK4/6i (palbociclib, ribociclib or abemaciclib) and fulvestrant, for the treatment of participants with locally advanced (inoperable) or metastatic HR+/HER2- breast cancer following either recurrence or progression on, or after (neo)adjuvant ET. The study comprises two parts (Phase Ib and Phase III); the recommended Phase III doses (RP3Ds) of capivasertib and CDK4/6i in combination with a fixed dose of fulvestrant will be determined in the open-label, dose finding Phase Ib part. The efficacy and safety of the capivasertib arm will be compared to the control arm in the randomised, open-label Phase III part. The Phase Ib part of the study consists of an open-label, 3-arm dose finding phase to determine the safe and well tolerated doses and schedules (RP3D) of capivasertib plus CDK4/6i (palbociclib, ribociclib, or abemaciclib) and fulvestrant (the latter administered at fixed dose and schedule, as per label) as triplet combinations in participants with ABC. The maximum tolerated doses (MTD) may also be determined. The Phase III part is an open-label, randomised study assessing the efficacy of the capivasertib arm (capivasertib plus investigator’s choice of CDK4/6i [palbociclib or ribociclib] and fulvestrant) versus the control arm (investigator’s choice of CDK4/6i [palbociclib or ribociclib] and fulvestrant) for the treatment of patients with locally advanced (inoperable) or metastatic HR+/HER2- breast cancer following recurrence or progression on or after endocrine therapy. The Phase III doses of capivasertib, palbociclib, and fulvestrant combination and capivasertib, ribociclib, and fulvestrant combination were identified in the Phase Ib part of this study, based on the safety and tolerability data that were reviewed and endorsed by an external Safety Review Committee (SRC). Abemaciclib is not planned to be included among the Phase III CDK4/6i options due to an increasing global preference for ribociclib and the anticipated increasing use of abemaciclib in the adjuvant setting.


Clinical Study Identifier: s24-01204
ClinicalTrials.gov Identifier: NCT04862663
Principal Investigator: Maryann J Kwa.
Other Investigators: Shridar Ganesan, Wanqing Iris Zhi, Danielle Seidman, Natalie Jill Klar, Annmarie Johnson-Rowe, Yelena Novik, Marleen I Meyers, Neil Vasan, Yael Simons, Akilah Monique Bryant, Nina D'Abreo, Douglas K Marks, Amanda Marie Buzolich, Gregory Edward Totero, Anastasiya Apanasyuk, Ruth Oratz, Stacy Antwi, Naomi Yu Ko, Elizabeth Comen, Chrystal Teran, Nancy Chan, Phyu Phyu Soe, Eliana Ferreira, Alexander A Hindenburg.


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