On December 11, 2023 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company (the Company), reported the design of the Phase II trial of alisertib for the treatment of patients with HER2-negative, hormone receptor-positive metastatic breast cancer (PUMA-ALI-1201) (Press release, Puma Biotechnology, DEC 11, 2023, View Source [SID1234638469]). Based on the Company’s interactions with the U.S. Food and Drug Administration (FDA), the Company will be initiating a Phase II trial of alisertib in combination with endocrine treatment (consisting of either anastrozole, exemestane, letrozole, fulvestrant or tamoxifen) in patients with chemotherapy-naïve HER2-negative, hormone receptor-positive 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. The Company has updated the presentation on its website to include a slide that describes the PUMA-ALI-1201 trial. The Company 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 (BID) 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 (ORR), duration of response (DOR), disease control rate (DCR) and progression-free survival (PFS). As a secondary objective, the Company will be evaluating each of these efficacy endpoints within biomarker subgroups in order to determine whether any biomarker subgroup correlates with better efficacy as has been seen in preclinical and clinical studies in other cancers including breast cancer and small cell lung cancer. The Company will then look to focus the future clinical development of alisertib in combination with endocrine therapy for patients with HER2-negative hormone receptor-positive breast cancer in patients with these biomarkers.
Based on its interactions with the FDA, the Company believes that this trial design will satisfy the FDA’s Project Optimus intended to find the optimal dose of alisertib in combination with endocrine therapy in patients with HER2-negative, hormone receptor-positive metastatic breast cancer to move into a pivotal Phase III trial. 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 investigator’s choice endocrine therapy versus placebo plus investigator’s choice endocrine therapy in patients with chemotherapy naïve HER2-negative, hormone receptor-positive metastatic breast cancer.
"There continues to be a need for new drugs for the treatment of metastatic HER2-negative, hormone receptor-positive breast cancer," said Alvin Wong, PharmD, Chief Scientific Officer of Puma Biotechnology. "The clinical trials of alisertib to date in HER2-negative, hormone receptor-positive metastatic breast cancer have demonstrated alisertib’s potential clinical benefit in this patient population, and we look forward to initiating the PUMA-ALI-1201 trial in 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 is 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 in order to protect the Company’s future profitability."