Puma Biotechnology, Inc. (NASDAQ: PBYI) 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-negative) 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 trial aims to determine the optimal dose of alisertib in this patient population and explore potential regulatory pathways for approval.
Trial Design and Objectives
The ALISCA™-Breast1 trial will enroll up to 150 patients, randomized (1:1:1) to receive alisertib at 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 specimens for biomarker analysis.
The primary objective is to determine the optimal alisertib dose in combination with endocrine therapy. Primary endpoints include objective response rate, duration of response, disease control rate, progression-free survival, and overall survival. A secondary endpoint involves evaluating these efficacy endpoints within biomarker subgroups to identify correlations with response. Puma plans to conduct biomarker analysis in parallel with the clinical trial and perform an initial interim analysis for safety and efficacy evaluation.
Regulatory Strategy and Future Plans
Based on the trial outcomes, Puma intends to meet 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 alisertib dose is identified, Puma plans to engage with global regulatory agencies to design a pivotal (Phase III) trial. The anticipated Phase III trial will be a randomized study 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.
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., the 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."
Puma Biotechnology's Perspective
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 believe that the data from the previous trial of alisertib monotherapy (published in Lancet Oncology) as well as the TBCRC 041 trial (published in JAMA Oncology), which tested alisertib alone and with fulvestrant, and the randomized trial of alisertib plus paclitaxel versus paclitaxel alone (published in JAMA Network Open) have demonstrated that alisertib is active in patients with HER2-negative, HR+ metastatic breast cancer and in biomarker focused subgroups. We look forward to enrollment in the ALISCA™-Breast1 trial and anticipate that we should have initial data from this trial in 2025."
