Puma Biotechnology, Inc. has announced the initiation of the ALISertib in CAncer (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. These patients must 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 plans 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 protocol requires patients to provide blood and tissue samples 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. Primary endpoints include objective response rate (ORR), duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Secondary endpoints involve evaluating these efficacy measures within biomarker subgroups to identify potential correlations between biomarkers and treatment response. Puma plans to conduct biomarker analysis concurrently with the clinical trial and intends to perform an initial interim analysis to assess safety and efficacy.
Regulatory Strategy and Future Plans
Based on the trial outcomes, Puma 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 dose of alisertib is identified, Puma intends to consult with global regulatory agencies regarding the design of a pivotal Phase III trial. The anticipated Phase III trial will 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
"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," said 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. "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, 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."
