On March 20, 2024 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company (the Company), reported that it has been notified by the U.S. Food and Drug Administration (FDA) that its Investigational New Drug Application (IND) submission has been reviewed, and Puma can proceed with the clinical development of alisertib for the treatment of patients with human epidermal growth factor receptor 2-negative (HER2-negative), hormone receptor-positive metastatic breast cancer in Puma’s Phase II ALISCA-Breast1 trial (Study PUMA-ALI-4201) (Press release, Puma Biotechnology, MAR 20, 2024, View Source [SID1234641308]). This trial will investigate alisertib in combination with endocrine treatment (consisting of either anastrozole, exemestane, letrozole, fulvestrant or tamoxifen) in chemotherapy-naïve patients with hormone receptor-positive, HER2-negative recurrent or metastatic breast cancer. Patients must 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 to be eligible for the trial. Puma plans to initiate this trial in the second half of 2024.
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Patients will be dosed with alisertib given at either 30 mg, 40 mg or 50 mg twice daily on days 1-3, 8-10 and 15-17 on a 28-day cycle in combination with the endocrine therapy of the investigator’s choice. Patients must not have been previously treated with the endocrine treatment that will be given in combination with alisertib in the trial. Each dose level will enroll up to 50 patients. Patients must provide blood samples and tissue-based biopsies so that biomarkers can be evaluated. The primary efficacy end points will include objective response rate, duration of response, disease control rate and progression-free survival. As a secondary endpoint, the Company will be evaluating each of these efficacy endpoints within biomarker subgroups in order to determine whether any biomarker subgroup correlates with response. The goal would be to enhance the efficacy in a biomarker subgroup to improve the efficacy of alisertib as previously seen in preclinical and clinical studies in other cancers, including breast cancer and small cell lung cancer.
Once the optimal alisertib dose is identified, the Company 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 investigators choice endocrine therapy versus placebo plus investigator’s choice endocrine therapy in patients with chemotherapy naïve HER2-negative, hormone receptor-positive metastatic breast cancer.
"Although there have been new drugs approved for the treatment of ER-positive HER2-negative metastatic breast cancer, there continues to be a need for new drugs and ones that specifically can address patients who have been previously treated with CDK 4/6 inhibitors," said Alvin Wong, Pharm.D., Chief Scientific Officer of Puma Biotechnology. "The TBCRC 041 trial, which was published in JAMA Oncology in March 2023, demonstrated that alisertib is among the first investigational targeted therapies to have demonstrated encouraging clinical activity and have been generally well tolerated in the setting of endocrine and CDK 4/6 inhibitor resistant metastatic breast cancer. We look forward to the initiation of the ALISCA-Breast1 trial in the second half of 2024."
Alan H. Auerbach, Chief Executive Officer and President of Puma Biotechnology, said, "We are excited to move forward with the development of alisertib in HER2-negative hormone receptor-positive metastatic breast cancer. We believe that the data from TBCRC 041, which tested alisertib alone and with fulvestrant, and the randomized trial of alisertib plus paclitaxel versus paclitaxel alone have demonstrated that alisertib was active in patients with HER2-negative, hormone receptor-positive metastatic breast cancer and in biomarker focused subgroups. We also recognize our fiscal responsibility to the shareholders of the Company and will be carefully managing the development expenses for alisertib so as not to potentially negatively impact the Company’s profitability."