On November 20, 2024 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported the initiation of its ALISertib in CAncer (ALISCA-Breast1) Phase II trial (PUMA-ALI-1201; NCT06369285) of alisertib in combination with endocrine therapy for the treatment of patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-negative) recurrent or metastatic breast cancer who have been previously treated with CDK 4/6 inhibitors and received at least two prior lines of endocrine therapy in the recurrent or metastatic setting (Press release, Puma Biotechnology, NOV 20, 2024, View Source [SID1234648532]). The ALISCA-Breast1 trial will enroll up to 150 patients who will be randomized (1:1:1) to receive alisertib dosed at either 30 mg, 40 mg or 50 mg twice daily on days 1-3, 8-10 and 15-17 in a 28-day cycle in combination with the endocrine therapy of the investigator’s choice. Patients must provide blood and tissue specimens so that biomarkers can be analyzed.

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"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"

The primary objective of the trial is to determine the optimal alisertib dose in combination with selected endocrine therapy. The primary endpoints of the trial include objective response rate, duration of response, disease control rate, progression-free survival, and overall survival. As a secondary endpoint, Puma will evaluate each of these efficacy endpoints within biomarker subgroups in order to determine whether any biomarker subgroup correlates with response. Puma will perform its biomarker analysis of the ALISCA-Breast1 trial in parallel with the execution of the clinical trial. Puma plans to perform an initial interim analysis for the evaluation of safety and efficacy.

Based upon the outcomes of the trial, Puma anticipates meeting with the U.S. Food and Drug Administration to explore the potential for an 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 regarding the design of a pivotal (Phase III) trial, which it anticipates will be a randomized trial 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.

"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."

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."