Puma Biotechnology, Inc. 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). 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. 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.