Puma Biotechnology has launched ALISCA™-Breast1, a Phase II clinical trial investigating alisertib in combination with endocrine therapy for patients with HER2-negative, hormone receptor-positive (HR-positive) metastatic breast cancer. The trial, which began in November 2024, marks a significant expansion of the company's oncology pipeline beyond its established NERLYNX® (neratinib) franchise.
Alisertib, a selective, small molecule, orally administered inhibitor of aurora kinase A, was licensed by Puma Biotechnology in September 2022. The company has strategically focused the drug's development on two major cancer types: small cell lung cancer and breast cancer.
Dual-Track Development Strategy
The ALISCA™-Breast1 trial represents the second Phase II study in Puma's alisertib clinical program. Earlier this year, in February 2024, the company initiated ALISCA™-Lung1, a Phase II trial evaluating alisertib as monotherapy for patients with extensive-stage small cell lung cancer.
"The initiation of our second Phase II trial for alisertib demonstrates our commitment to exploring this compound's potential across multiple cancer types with significant unmet needs," said Alan H. Auerbach, CEO of Puma Biotechnology, in a company statement.
Strategic Pipeline Expansion
Puma Biotechnology's development of alisertib represents a strategic expansion of its oncology portfolio. The company's flagship product, NERLYNX® (neratinib), received FDA approval in 2017 for extended adjuvant treatment of adult patients with early-stage HER2-overexpressed/amplified breast cancer following adjuvant trastuzumab-based therapy.
In February 2020, NERLYNX gained additional FDA approval in combination with capecitabine for treating 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.
The European Commission granted marketing authorization for NERLYNX in 2018 for extended adjuvant treatment of adult patients with early-stage hormone receptor-positive HER2-overexpressed/amplified breast cancer who are less than one year from completion of prior adjuvant trastuzumab-based therapy.
Mechanism of Action and Therapeutic Potential
Alisertib's mechanism as an aurora kinase A inhibitor offers a novel approach to cancer treatment. Aurora kinases play crucial roles in cell division, and their dysregulation has been implicated in various cancers. By targeting aurora kinase A specifically, alisertib may disrupt cancer cell proliferation while potentially minimizing effects on normal cells.
The combination approach being tested in ALISCA™-Breast1—pairing alisertib with endocrine therapy—reflects current understanding of resistance mechanisms in HR-positive breast cancer and the potential for kinase inhibitors to enhance response to hormonal treatments.
Corporate Developments
Alongside its clinical progress, Puma Biotechnology recently announced inducement awards for new non-executive employees. On December 2, 2024, the company's Board of Directors Compensation Committee approved a restricted stock unit award covering 7,500 shares of Puma common stock to a new employee. This follows a similar award in November covering 5,625 shares to another new employee.
These awards, granted under Puma's 2017 Employment Inducement Incentive Award Plan, vest over three years and align with the company's growth strategy as it expands its clinical programs.
As Puma advances its alisertib clinical trials, the oncology community will be watching closely for efficacy and safety data that could potentially establish new treatment options for patients with HR-positive metastatic breast cancer and extensive-stage small cell lung cancer.
