Puma Biotech Presents Phase II Alisertib Study Results in Endocrine-Resistant Metastatic Breast Cancer

Puma Biotechnology, Inc. (NASDAQ: PBYI), a leading biopharmaceutical company, recently disclosed important biomarker findings from a Phase II clinical trial comparing alisertib alone to a combination of alisertib and fulvestrant. This study focuses on patients suffering from endocrine and CDK4/6 inhibitor (CDK 4/6i)-resistant, HER2-negative, hormone receptor-positive metastatic breast cancer. The results were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago and are part of a larger effort by the Translational Breast Cancer Research Consortium (TBCRC).

Tufia Haddad and her team published the trial results in JAMA Oncology in March 2023. The study demonstrated promising clinical activity in both treatment arms, with an overall response rate of around 20% and a median progression-free survival of about 5.5 months. The safety profiles of both treatment regimens were also deemed tolerable.

A poster session at the ASCO meeting, led by Dr. Karthik Giridhar of the Mayo Clinic, provided further insights into the molecular profiling performed during the trial. The poster, identified as Abstract #1037 and Poster Bd #15, specifically discussed the molecular profiling of serial liquid biopsy specimens using cell-free DNA (cfDNA) and circulating tumor cells (CTCs).

Key somatic mutations in ESR1, PIK3CA, PTEN, and AKT1 were identified from pre-treatment plasma samples. Notably, patients with PIK3CA mutations experienced shorter progression-free survival (PFS), whereas ESR1 mutations showed no significant impact on PFS. Additionally, lower pre-treatment CTC counts correlated with longer PFS, and similar trends were observed with lower methylated tumor fraction percentages in plasma samples at the end of the first treatment cycle.

Dr. Tufia Haddad emphasized the potential significance of Aurora Kinase A in the context of endocrine- and CDK4/6i-resistant breast cancers. She noted the importance of identifying which patients could benefit the most from alisertib, which could guide future clinical trials focusing on specific biomarker-defined populations.

Dr. Giridhar expressed satisfaction with the opportunity to evaluate liquid biopsy biomarkers in the TBCRC 041 trial. He highlighted that continued biomarker analyses from this and future trials could help clarify the patient populations that would benefit most from alisertib treatment.

Alan H. Auerbach, CEO and President of Puma Biotechnology, reiterated the company's commitment to developing alisertib for biomarker-focused populations. He emphasized that the results from this biomarker analysis enhance the understanding of which patients might derive the greatest benefit from alisertib, supporting future clinical studies in endocrine- and CDK4/6i-resistant metastatic breast cancer.

Puma Biotechnology is dedicated to improving cancer care through innovative products. The company obtained the global development and commercialization rights to PB272 (neratinib) in 2011. Neratinib received FDA approval for extended adjuvant treatment of early-stage HER2-positive breast cancer in 2017 and for advanced or metastatic HER2-positive breast cancer in combination with capecitabine in 2020. In 2018, the European Commission also granted marketing authorization for neratinib for similar indications.

In September 2022, Puma acquired exclusive rights to develop and commercialize alisertib, an investigational inhibitor of aurora kinase A. Puma is initially focusing on treating small cell lung cancer and breast cancer. In February 2024, the company initiated a Phase II clinical trial, ALISCA-Lung 1, evaluating alisertib monotherapy for extensive-stage small cell lung cancer.

Puma Biotechnology remains focused on advancing the development of alisertib and other innovative cancer treatments to improve the outcomes for patients with difficult-to-treat cancers.