Puma Biotechnology has announced the initiation of the ALISCA™-Breast1 Phase II trial (PUMA-ALI-1201; NCT06369285) evaluating alisertib in combination with endocrine therapy for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) recurrent or metastatic breast cancer. This trial targets patients who have previously been treated with CDK 4/6 inhibitors and have received at least two prior lines of endocrine therapy in the recurrent or metastatic setting.
The ALISCA™-Breast1 trial is designed to enroll up to 150 patients. Participants will be randomized in a 1:1:1 ratio to receive alisertib at doses of 30 mg, 40 mg, or 50 mg twice daily on days 1-3, 8-10, and 15-17 of a 28-day cycle, combined with the investigator's choice of endocrine therapy. The trial also requires patients to provide blood and tissue specimens for biomarker analysis.
Trial Objectives and Endpoints
The primary objective of the ALISCA™-Breast1 trial is to determine the optimal dose of alisertib when combined with endocrine therapy. Key primary endpoints include objective response rate (ORR), duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Puma Biotechnology will also evaluate these efficacy endpoints within biomarker subgroups to identify potential correlations between biomarkers and treatment response. An initial interim analysis is planned to evaluate safety and efficacy.
Future Regulatory Plans
Based on the trial's outcomes, Puma Biotechnology anticipates engaging with the U.S. Food and Drug Administration (FDA) to discuss a potential approval pathway for alisertib in HER2-negative, HR+ metastatic breast cancer. Once the optimal alisertib dose is identified, the company intends to consult with global regulatory agencies regarding the design of a pivotal Phase III trial. This Phase III trial is expected to be a randomized study comparing alisertib plus investigator’s choice of endocrine therapy versus placebo plus investigator’s choice of endocrine therapy in patients with HER2-negative, HR+ metastatic breast cancer.
Expert Commentary
Joyce A. O’Shaughnessy, M.D., Celebrating Women Chair in Breast Cancer Research at Baylor University Medical Center, Texas Oncology, Sarah Cannon Research Institute in Dallas, Texas, commented, “Additional therapies are needed for patients with HER2-negative, HR+ metastatic breast cancer whose disease progresses on CDK4/6 inhibitors in the first-line setting. 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 ALISCA™-Breast1 trial to definitively determine the clinical impact of this treatment.”
Alan H. Auerbach, Chief Executive Officer, President and Founder of Puma Biotechnology, stated, “We are excited to initiate this Phase II trial and to move forward with the development of alisertib in HER2-negative HR+ metastatic breast cancer... We look forward to enrollment in the ALISCA™-Breast1 trial and anticipate that we should have initial data from this trial in 2025.”
