Puma Biotechnology initiated its ALISertib in CAncer (ALISCA™-Breast1) Phase II trial (PUMA-ALI-1201; NCT06369285). This trial investigates alisertib combined with endocrine therapy for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-negative) recurrent or metastatic breast cancer. The study targets patients previously treated with CDK 4/6 inhibitors and at least two prior lines of endocrine therapy in the recurrent or metastatic setting.
The ALISCA™-Breast1 trial will enroll up to 150 patients, randomly assigned to receive one of three alisertib dosages (30mg, 40mg, or 50mg) twice daily on days 1-3, 8-10, and 15-17 of a 28-day cycle. This treatment will be administered alongside the investigator’s choice of endocrine therapy. Mandatory blood and tissue samples will be collected for biomarker analysis. The trial’s primary objective is to identify the optimal alisertib dose when combined with selected endocrine therapy. Key endpoints include objective response rate, response duration, disease control rate, progression-free survival, and overall survival. Puma will also evaluate these endpoints within biomarker subgroups to identify any correlations with treatment response. This biomarker analysis will occur concurrently with the clinical trial.
Puma plans an interim analysis to assess safety and efficacy. Depending on the trial’s results, Puma intends to consult with the U.S. Food and Drug Administration to discuss a potential approval pathway for alisertib in this specific breast cancer type. After determining the optimal alisertib dose, Puma will collaborate with global regulatory agencies to design a pivotal Phase III trial. This subsequent trial is anticipated to be a randomized study comparing alisertib plus investigator’s choice endocrine therapy against placebo plus investigator’s choice endocrine therapy in the same patient population.
Puma believes existing data from previous alisertib trials, including a monotherapy trial, the TBCRC 041 trial (testing alisertib alone and with fulvestrant), and a randomized trial of alisertib plus paclitaxel versus paclitaxel alone, demonstrate alisertib’s activity in HER2-negative, HR+ metastatic breast cancer, particularly within specific biomarker subgroups. Initial data from the ALISCA™-Breast1 trial is expected in 2025.
Puma Biotechnology focuses on developing and commercializing innovative cancer treatment products. The company holds global development and commercialization rights to NERLYNX® (neratinib), an FDA-approved treatment for extended adjuvant treatment of early-stage HER2-overexpressed/amplified breast cancer following adjuvant trastuzumab-based therapy, and for use in combination with capecitabine for advanced or metastatic HER2-positive breast cancer in patients previously treated with two or more anti-HER2 regimens. NERLYNX also holds European Commission marketing authorization for extended adjuvant treatment in a similar patient population. Puma also licensed alisertib, an aurora kinase A inhibitor, in September 2022, initially focusing its development on small cell lung cancer and breast cancer. This led to the initiation of ALISCA™-Lung1, a Phase II alisertib monotherapy trial for extensive-stage small cell lung cancer, in February 2024, followed by the ALISCA™-Breast1 trial in November 2024.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
