Puma Biotechnology has announced the initiation of the ALISCA™-Breast1 Phase II trial (PUMA-ALI-1201; NCT06369285) to assess the efficacy and safety of 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 focuses on 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 used in combination with endocrine therapy. The 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 also plans to evaluate these efficacy endpoints within biomarker subgroups to identify potential correlations between biomarkers and treatment response. An initial interim analysis will be performed to assess safety and efficacy.
Rationale and Future Plans
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, noted the need for additional therapies for patients with HER2-negative, HR+ metastatic breast cancer whose disease progresses on CDK4/6 inhibitors. She cited the TBCRC 041 trial, which indicated that alisertib has clinical activity in endocrine therapy and CDK4/6 inhibitor-resistant metastatic breast cancer with good tolerability, and expressed anticipation for the ALISCA™-Breast1 trial.
Alan H. Auerbach, Chief Executive Officer, President and Founder of Puma Biotechnology, stated that previous trials have demonstrated alisertib's activity in patients with HER2-negative, HR+ metastatic breast cancer and in biomarker-focused subgroups. He anticipates initial data from the ALISCA™-Breast1 trial in 2025. Based on the trial outcomes, Puma intends to meet with the FDA to explore a potential approval pathway for alisertib in HER2-negative, HR+ metastatic breast cancer. Once the optimal dose is identified, Puma plans to engage with global regulatory agencies to design a pivotal Phase III trial, which is expected to be a randomized trial comparing alisertib plus investigator’s choice endocrine therapy versus placebo plus investigator’s choice endocrine therapy in patients with HER2-negative, HR+ metastatic breast cancer.
