Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, announced 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. 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.

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.”

About Puma Biotechnology

Puma Biotechnology, Inc. is a biopharmaceutical company with a focus on the development and commercialization of innovative products to enhance cancer care. Puma in-licensed the global development and commercialization rights to PB272 (neratinib, oral), in 2011. Neratinib, oral was approved by the U.S. Food and Drug Administration in 2017 for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, following adjuvant trastuzumab-based therapy, and is marketed in the United States as NERLYNX® (neratinib) tablets. In February 2020, NERLYNX was also approved by the FDA in combination with capecitabine for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting. NERLYNX was granted marketing authorization by the European Commission in 2018 for the extended adjuvant treatment of adult patients with early stage HR+, HER2-overexpressed/amplified breast cancer and who are less than one year from completion of prior adjuvant trastuzumab-based therapy. NERLYNX® is a registered trademark of Puma Biotechnology, Inc.

In September 2022, Puma entered into an exclusive license agreement for the development and commercialization of the anti-cancer drug alisertib, a selective, small molecule, orally administered inhibitor of aurora kinase A. Initially, Puma intends to focus the development of alisertib on the treatment of small cell lung cancer and breast cancer. In February 2024, Puma initiated ALISCA™-Lung1, a Phase II clinical trial of alisertib monotherapy for the treatment of patients with extensive-stage small cell lung cancer. In November 2024, Puma initiated ALISCA™-Breast1, a Phase II clinical trial of alisertib in combination with endocrine therapy for the treatment of patients with HER2-negative, HR+ metastatic breast cancer.

Further information about Puma Biotechnology may be found at https://www.pumabiotechnology.com.

Forward-Looking Statements

This press release contains forward-looking statements, including statements regarding Puma’s expectations regarding the development of alisertib and clinical trials involving alisertib. All forward-looking statements involve risks and uncertainties that could cause Puma’s actual results to differ materially from the anticipated results and expectations expressed in these forward-looking statements. These statements are based on current expectations, forecasts and assumptions, and actual outcomes and results could differ materially from these statements due to a number of factors, which include, but are not limited to, the risk factors disclosed in the periodic and current reports filed by Puma with the Securities and Exchange Commission from time to time, including Puma’s Annual Report on Form 10-K for the year ended December 31, 2023 and subsequent reports. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Puma assumes no obligation to update these forward-looking statements, except as required by law.

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