Michael A. Carducci, MD, professor of oncology, AEGON Professor of Prostate Cancer Research, Johns Hopkins Medicine, discusses the significance of two ongoing clinical trials in prostate cancer: the phase 3 CAPItello-280 trial (NCT05348577) and phase 3 INDICATE study (EA8191; NCT04423211).

The randomized CAPItello-280 trial was designed to build on preclinical safety and efficacy data by evaluating the addition of the AKT1/2/3 inhibitor capivasertib to standard doxetaxel in the frontline treatment of patients with metastatic castration-resistant prostate cancer (mCRPC), Carducci introduces. Docetaxel is a standard of care (SOC) for patients with mCRPC who progress on an androgen receptor (AR) targeted agent. However, these patients often develop resistance to chemotherapy 

and have a poor overall survival (OS). Accordingly, several trials have investigated the addition of other agents to docetaxel to improve clinical outcomes, he says.

Previously reported data from the phase 2 ProCAID trial (NCT02121639) demonstrated that the addition of capivasertib to docetaxel did extend overall survival (OS) in patients with mCRPC, Carducci continues. However, the regimen did not lead to a difference in the primary end point of composite progression-free survival (PFS). Follow-up analysis of this trial suggested that a limited population of patients who were previously treated with an AR targeted agent received this OS benefit.

In CAPItello-280, the combination’s efficacy and safety will be compared with placebo and docetaxel in patients with mCRPC who have not received prior chemotherapy for mCRPC but have progressed on an AR targeted agent, Carducci states. The trial’s primary end point is OS, and secondary end points include radiographic PFS, time to pain progression, symptomatic skeletal-related events, safety and tolerability, patient-reported outcomes, and pharmacokinetic analysis.

Other exciting future studies in prostate cancer include the INDICATE trial, which is evaluating local or systemic therapy in patients with biochemically-recurrent prostate cancer after prostatectomy, Carducci adds. The trial will evaluate how PET imaging can be used to determine its predictive value, and inform treatment selection in clinical practice, he states. The hope is that the modality improves clinical decision making, leading to increased patient responses to treatment, Carducci concludes. 

Dr. Carducci reports serving as a consultant or in an advisory role for Acrivon Therapeutics, AstraZeneca, Exelixis, Pfizer, Sanofi; he reports receiving institutional research funding from Arcus Biosciences, Celgene/Bristol-Myers Squibb, Merck, Pfizer

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Michael A. Carducci, MD, discusses the significance of two ongoing clinical trials in prostate cancer: the phase 3 CAPItello-280 trial (NCT05348577) and phase 3 INDICATE study (EA8191; NCT04423211).

Michael A. Carducci, MD, FACP, Sidney Kimmel Comprehensive Cancer Center of Johns Hopkins Hospital

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Dr. Carducci on the Ongoing CAPItello-280 Trial in mCRPC