Puma Biotechnology Announces FDA Allowance to Proceed Under IND for Alisertib in HER2-Negative, Hormone Receptor-Positive Metastatic Breast Cancer

Rhea-AI Summary

Puma Biotechnology, Inc. (PBYI) receives FDA notification to proceed with the clinical development of alisertib for HER2-negative, hormone receptor-positive metastatic breast cancer. The Phase II ALISCA-Breast1 trial will investigate alisertib in combination with endocrine treatment, targeting patients previously treated with CDK 4/6 inhibitors. The trial aims to identify optimal dosing, biomarker evaluation, and efficacy endpoints to potentially enhance alisertib's efficacy. Puma plans to initiate the trial in the second half of 2024.

Insights

Oncology Doctor

The FDA's clearance for Puma Biotechnology to proceed with the Phase II trial for alisertib marks a significant step in addressing the unmet medical needs of patients with hormone receptor-positive, HER2-negative metastatic breast cancer. The clinical strategy to focus on patients previously treated with CDK 4/6 inhibitors, who have limited treatment options, could potentially offer a new therapeutic avenue. The integration of biomarkers to refine responsiveness is a critical advancement, potentially leading to personalized treatment regimens that could enhance patient outcomes.

Medical Research Analyst

From a research perspective, the progression to a Phase II trial is indicative of promising preclinical and Phase I results. The emphasis on biomarker subgroups within the trial design is noteworthy as it aligns with the industry's shift towards precision medicine. The careful selection of endocrine therapy combinations and the structured dose-escalation plan demonstrate a methodical approach to ascertain the optimal therapeutic window for alisertib. The study's endpoints, particularly the objective response rate and progression-free survival, are key indicators of the drug's efficacy that will be closely monitored by stakeholders.

Market Analyst

For investors, the initiation of this trial represents both opportunity and risk. The potential for alisertib to fulfill a niche within the metastatic breast cancer treatment landscape could lead to significant market penetration, especially if the biomarker strategy proves successful in enhancing efficacy. However, the trial's outcomes won't materialize until post-2024 and as such, the impact on Puma Biotechnology's stock will be subject to the company's ability to manage development costs without jeopardizing profitability, as highlighted by the CEO. Investors will need to weigh the long-term potential against the short-term financial considerations.

LOS ANGELES--(BUSINESS WIRE)-- Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company (the Company), 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.

“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.”

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), PB272 (neratinib, intravenous) and PB357. 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 hormone receptor-positive 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, an investigational, 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-Lung 1, a Phase II clinical trial of alisertib monotherapy for the treatment of patients with extensive-stage small cell lung 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 anticipated milestones and the development of 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.

View source version on businesswire.com: https://www.businesswire.com/news/home/20240320193286/en/

Alan H. Auerbach or Mariann Ohanesian, Puma Biotechnology, Inc., +1 424 248 6500

info@pumabiotechnology.com

ir@pumabiotechnology.com

David Schull, Russo Partners, +1 212 845 4200

david.schull@russopartnersllc.com

Source: Puma Biotechnology, Inc.

FAQ

What is the purpose of the Phase II ALISCA-Breast1 trial for Puma Biotechnology (PBYI)?

The trial aims to investigate alisertib in combination with endocrine treatment for HER2-negative, hormone receptor-positive metastatic breast cancer.

When does Puma Biotechnology (PBYI) plan to initiate the ALISCA-Breast1 trial?

Puma plans to start the trial in the second half of 2024.

What are the primary efficacy endpoints of the ALISCA-Breast1 trial?

The primary endpoints include objective response rate, duration of response, disease control rate, and progression-free survival.

Why is there a need for new drugs in the treatment of HER2-negative, hormone receptor-positive metastatic breast cancer according to Puma Biotechnology (PBYI)?

There is a need for drugs that can specifically address patients who have been previously treated with CDK 4/6 inhibitors.

Who is the Chief Scientific Officer of Puma Biotechnology (PBYI) and what did they mention regarding the ALISCA-Breast1 trial?

Alvin Wong mentioned the need for new drugs and the encouraging clinical activity of alisertib in the setting of endocrine and CDK 4/6 inhibitor resistant metastatic breast cancer.

What is the stance of the CEO and President of Puma Biotechnology (PBYI) regarding the development of alisertib for metastatic breast cancer?

Alan H. Auerbach is excited about the development of alisertib and recognizes the fiscal responsibility to shareholders in managing development expenses.

What is the anticipated design of the pivotal (Phase III) trial for alisertib according to Puma Biotechnology (PBYI)?

The company plans a randomized trial of alisertib plus endocrine therapy versus placebo plus endocrine therapy in patients with chemotherapy naive HER2-negative, hormone receptor-positive metastatic breast cancer.

What did the TBCRC 041 trial demonstrate regarding alisertib in the setting of metastatic breast cancer?

The trial showed that alisertib demonstrated encouraging clinical activity and was generally well tolerated in patients with endocrine and CDK 4/6 inhibitor resistant metastatic breast cancer.

How does Puma Biotechnology (PBYI) plan to enhance the efficacy of alisertib in the ALISCA-Breast1 trial?

The company aims to evaluate efficacy endpoints within biomarker subgroups to potentially improve alisertib's efficacy.

What is the dosing regimen of alisertib in the ALISCA-Breast1 trial?

Patients will be dosed with alisertib at either 30 mg, 40 mg, or 50 mg twice daily on specific days in a 28-day cycle in combination with endocrine therapy.