Puma Biotechnology Initiates Phase 2 Trial of Alisertib for HR+/HER2- Metastatic Breast Cancer

• Puma Biotechnology has begun a Phase 2 trial (ALISCA™-Breast1) to evaluate alisertib combined with endocrine therapy for hormone receptor-positive, HER2-negative metastatic breast cancer.
• The trial will enroll up to 150 patients who have previously received CDK 4/6 inhibitors and at least two prior endocrine therapies, with initial data expected in 2025.
• The primary objective is to determine the optimal dose of alisertib, with endpoints including objective response rate, duration of response, and progression-free survival.
• Puma plans to discuss potential FDA approval pathways following the trial, with a future Phase 3 trial potentially comparing alisertib plus endocrine therapy to placebo plus endocrine therapy.

Puma Biotechnology has announced the initiation of the ALISCA™-Breast1 Phase 2 trial, 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. The trial, identified as PUMA-ALI-1201 (NCT06369285), aims to address the unmet need for effective treatments in patients who have progressed on CDK 4/6 inhibitors and prior endocrine therapies.

The ALISCA™-Breast1 trial will 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. Patients are required 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. Key endpoints include objective response rate, duration of response, disease control rate, progression-free survival, and overall survival. Puma Biotechnology will also evaluate these efficacy endpoints within biomarker subgroups to identify potential correlations between biomarkers and treatment response.

Regulatory Strategy and Future Plans

Following the completion of the Phase 2 trial, Puma Biotechnology intends to engage with the U.S. Food and Drug Administration (FDA) to discuss potential approval pathways for alisertib in HER2-negative, HR+ metastatic breast cancer. The company anticipates a future Phase 3 trial comparing alisertib plus investigator’s choice endocrine therapy to placebo plus investigator’s choice endocrine therapy in the same patient population.

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, noted the need for additional therapies for patients with HER2-negative, HR+ metastatic breast cancer whose disease progresses on CDK4/6 inhibitors. She highlighted the promising clinical activity and tolerability of alisertib observed in the TBCRC 041 trial and expressed anticipation for the ALISCA™-Breast1 trial results.

Puma Biotechnology's Perspective

Alan H. Auerbach, Chief Executive Officer, President and Founder of Puma Biotechnology, expressed enthusiasm for the initiation of the Phase 2 trial and the continued development of alisertib in HER2-negative HR+ metastatic breast cancer. He cited data from previous trials, including studies published in Lancet Oncology, JAMA Oncology, and JAMA Network Open, which demonstrated alisertib's activity in this patient population and in biomarker-focused subgroups. Initial data from the ALISCA™-Breast1 trial is expected in 2025.