Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, has announced the launch of its ALISCA™-Breast1 Phase II trial (PUMA-ALI-1201; NCT06369285). The study will evaluate alisertib, in combination with endocrine therapy, for the treatment of hormone receptor-positive (HR+), HER2-negative recurrent or metastatic breast cancer. Eligible patients must have previously been treated with CDK 4/6 inhibitors and have received at least two prior lines of endocrine therapy. The trial aims to enroll up to 150 patients, who will be randomly assigned to receive alisertib at doses of 30 mg, 40 mg, or 50 mg twice daily on specific days of a 28-day cycle, alongside the endocrine therapy of the investigator’s choice. Blood and tissue samples will be collected for biomarker analysis.
The primary goal of the ALISCA™-Breast1 Phase II trial is to identify the optimal alisertib dose when combined with selected endocrine therapies. Key endpoints include objective response rate, duration of response, disease control rate, progression-free survival, and overall survival. As a secondary objective, Puma will evaluate these efficacy measures across biomarker subgroups to determine if specific biomarkers correlate with treatment response. Biomarker analysis will be conducted alongside the clinical trial. Puma plans to conduct an interim analysis to assess the safety and efficacy of the treatment.
Depending on the trial outcomes, Puma intends to meet with the U.S. Food and Drug Administration (FDA) to discuss potential approval pathways for alisertib in HER2-negative, HR+ metastatic breast cancer. Once the optimal dose is identified, the company plans to engage with global regulatory agencies regarding the design of a Phase III pivotal trial. This trial will likely compare alisertib plus investigator’s choice endocrine therapy to placebo plus endocrine therapy in HER2-negative, HR+ metastatic breast cancer patients.
“Patients with HER2-negative, HR+ metastatic breast cancer whose disease progresses on CDK4/6 inhibitors need additional treatment options,” said Dr. Joyce A. O’Shaughnessy, a leading breast cancer researcher. “The TBCRC 041 trial showed that alisertib demonstrated significant clinical activity in this setting, with good tolerability. I look forward to seeing further evaluation of alisertib in the ALISCA™-Breast1 trial to determine its full clinical potential.”
Alan H. Auerbach, CEO of Puma, added, “We are excited to start this Phase II trial and continue developing alisertib for HER2-negative HR+ metastatic breast cancer. Previous studies, including trials published in Lancet Oncology, JAMA Oncology, and JAMA Network Open, have shown that alisertib is active in these patients and in biomarker-driven subgroups. We look forward to enrolling patients in ALISCA™-Breast1 and anticipate initial results in 2025.”
About Puma Biotechnology
Puma Biotechnology, Inc. is a biopharmaceutical company focused on developing innovative cancer treatments. The company acquired global rights to PB272 (neratinib) in 2011. Neratinib was approved by the FDA in 2017 for extended adjuvant treatment of early-stage HER2-positive breast cancer. It is marketed in the U.S. as NERLYNX® (neratinib) tablets. In 2020, NERLYNX was also approved for use with capecitabine in treating advanced HER2-positive breast cancer.
In September 2022, Puma entered into an exclusive license agreement to develop alisertib, a selective aurora kinase A inhibitor. The company is focusing alisertib’s development on small cell lung cancer and breast cancer. In February 2024, Puma initiated the ALISCA™-Lung1 Phase II trial of alisertib for extensive-stage small cell lung cancer. In November 2024, the ALISCA™-Breast1 Phase II trial was launched to evaluate alisertib in combination with endocrine therapy for HER2-negative, HR+ metastatic breast cancer.
