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 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, addressing a critical unmet need in this patient population.
Trial Design and Objectives
The ALISCA™-Breast1 trial is designed to enroll up to 150 patients, 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. A key component of the trial is the requirement for patients to provide blood and tissue specimens for biomarker analysis.
The primary objective of the 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 an initial interim analysis to evaluate safety and efficacy.
Clinical Significance and Future Plans
Joyce A. O’Shaughnessy, M.D., Celebrating Women Chair in Breast Cancer Research at Baylor University Medical Center, emphasized the need for additional therapies for patients whose disease progresses on CDK4/6 inhibitors. She noted that prior trials, such as TBCRC 041, have indicated impressive clinical activity and good tolerability of alisertib in endocrine therapy and CDK4/6 inhibitor-resistant metastatic breast cancer.
Alan H. Auerbach, CEO, President, and Founder of Puma Biotechnology, expressed excitement about the trial's initiation and the potential of alisertib in HER2-negative, HR+ metastatic breast cancer. He highlighted previous trials demonstrating alisertib's activity in this patient population and in biomarker-focused subgroups. The company anticipates initial data from this trial in 2025 and plans to engage with global regulatory agencies regarding the design of a pivotal Phase III trial, contingent on the Phase II outcomes. The anticipated Phase III trial would be a randomized study of alisertib plus investigator’s choice endocrine therapy versus placebo plus investigator’s choice endocrine therapy in patients with HER2-negative, HR+ metastatic breast cancer.
Alisertib's Potential in Breast Cancer Treatment
Alisertib is a selective, small molecule, orally administered inhibitor of aurora kinase A. Puma Biotechnology in-licensed alisertib in September 2022, initially focusing its development on small cell lung cancer and breast cancer. This trial represents a significant step in evaluating alisertib's potential to address the unmet needs of patients with HR+/HER2- metastatic breast cancer who have progressed on existing therapies.
