Puma Biotechnology has commenced the Phase 2 ALISCA-Breast1 trial to assess the efficacy and safety of alisertib, an oral Aurora A kinase inhibitor, in combination with endocrine therapy for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer. The study, which has recently begun enrolling patients, seeks to determine the optimal dose of alisertib when used alongside endocrine therapy in this patient population.
The ALISCA-Breast1 trial is designed to enroll approximately 150 patients with HR+/HER2- recurrent or metastatic breast cancer who have previously been treated with CDK4/6 inhibitors and at least two lines of endocrine therapy. Participants will be randomly assigned to one of three treatment arms, receiving alisertib at doses of 30mg, 40mg, or 50mg twice daily, in addition to endocrine therapy selected by the investigator. The primary objective of the study is to determine the optimal dose of alisertib plus endocrine therapy, with key endpoints including objective response rate (ORR), duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).
Biomarker Analysis and Study Objectives
In addition to assessing the clinical efficacy of alisertib, the ALISCA-Breast1 trial incorporates a comprehensive biomarker analysis. Patients will provide blood and tissue samples at baseline to enable researchers to explore potential correlations between biomarkers and treatment response. The secondary objectives of the study include evaluating the same efficacy endpoints (ORR, DoR, DCR, PFS, and OS) within biomarker-defined subgroups.
According to Puma Biotechnology, initial data from the ALISCA-Breast1 trial is anticipated in 2025. Following the completion of the Phase 2 study and the determination of the optimal alisertib dose, the company plans to engage with the FDA to discuss a potential approval pathway for alisertib in HR+/HER2- metastatic breast cancer. A subsequent Phase 3 trial is planned to compare alisertib plus endocrine therapy to placebo plus endocrine therapy.
Clinical Context and Rationale
Metastatic breast cancer remains a significant clinical challenge, with a need for additional therapies for patients whose disease progresses on CDK4/6 inhibitors in the first-line setting. Alisertib has demonstrated promising clinical activity in prior trials, including the TBCRC 041 trial, which showed encouraging results in endocrine therapy and CDK4/6 inhibitor-resistant metastatic breast cancer. These findings support the further evaluation of alisertib in the ALISCA-Breast1 trial to definitively determine its clinical impact.
"Additional therapies are needed for patients with HER2-negative, HR-positive metastatic breast cancer whose disease progresses on CDK4/6 inhibitors in the first-line setting," said Dr. Joyce A. O’Shaughnessy, Celebrating Women Chair in Breast Cancer Research at Baylor University Medical Center, Texas Oncology, Sarah Cannon Research Institute in Dallas, Texas. "The results from the TBCRC 041 trial indicated that alisertib has impressive clinical activity in the setting of endocrine therapy and CDK4/6 inhibitor-resistant metastatic breast cancer, with good tolerability. I look forward to the further evaluation of alisertib in the ALISCATM-Breast1 trial to definitively determine the clinical impact of this treatment."
