On June 2, 2024 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported the presentation of biomarker findings from a Phase II randomized clinical trial of alisertib alone vs. alisertib + fulvestrant for the treatment of patients with endocrine and CDK4/6 inhibitor (CDK 4/6i) resistant, human epidermal growth factor receptor 2-negative (HER2-negative), hormone receptor-positive metastatic breast cancer (TBCRC 041; Clinicaltrials.gov identifier NCT02860000) at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting currently being held in Chicago (Press release, Puma Biotechnology, JUN 2, 2024, View Source [SID1234643965]). The Phase II trial was conducted through the Translational Breast Cancer Research Consortium (TBCRC). Results were published by Tufia Haddad et al. (JAMA Oncology, March 2023) and reported promising clinical activity in both arms (overall response rate 19.6% vs. 20.0% and median progression-free survival 5.6 months vs. 5.4 months for alisertib vs. alisertib + fulvestrant, respectively) and a tolerable safety profile.

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The poster (Abstract #1037, Poster Bd #15), entitled, "Molecular profiling of serial liquid biopsy specimens utilizing cell free DNA (cfDNA) and circulating tumor cells (CTCs) in TBCRC 041: A phase II study of alisertib in endocrine resistant metastatic breast cancer (MBC)," was presented at the Breast Cancer – Metastatic Poster Session by Karthik Giridhar, MD, Mayo Clinic, on June 2 at 9:00 a.m. CDT.

Somatic mutations from cell-free DNA derived from pre-treatment plasma were identified in ESR1 (n=45; 56.38%), PIK3CA (n=39; 48.8%), PTEN (n=13; 16.3%), and AKT1 (n=9; 11.3%). Patients with PIK3CA mutation experienced decreased progression-free survival (PFS) (HR 1.8; 95%CI: 1.1 -2.9, p=0.0225) while ESR1 mutation did not impact PFS (p=0.594).

Circulating tumors cells (CTCs) and methylated tumor fraction percentage (mTF) were evaluated in pre-treatment and at the end of cycle 1 (EOC1). Lower CTCs in pre-treatment samples were associated with longer PFS (7.4 months for CTC count <5 vs. 4.5 months for CTC count ≥5, HR=1.8; 95%CI: 1.1-3.0; p=0.018). In EOC1 plasma, lower mTF was associated with longer PFS (11.5 months for mTF ≤1% vs. 3.2 months for mTF>1%, HR 3.0; 95% CI: 1.6-5.2, p<0.001). Additional biomarker analyses are underway.

"Aurora Kinase A has potential importance in the setting of endocrine- and CDK4/6i-resistance," stated Tufia Haddad, MD, Professor of Oncology and Co-Leader of Platform and Digital Innovation, Mayo Clinic Comprehensive Cancer Center. "Further understanding of which patients may derive the greatest benefit to alisertib in the evolving landscape of endocrine- and CDK4/6i-resistant metastatic breast cancer may help us to focus on biomarker-defined populations that can be studied in future clinical trials of alisertib."

Dr. Giridhar, a co-investigator of the trial, said, "We are pleased to have had the opportunity to evaluate liquid biopsy biomarkers for TBCRC 041. Ongoing biomarker analysis from this and future trials of alisertib in endocrine- and CDK4/6i-resistant breast cancer may help clarify which patients could benefit most from alisertib."

Alan H. Auerbach, Chief Executive Officer and President of Puma Biotechnology, said, "We are committed to the development of alisertib in biomarker-focused populations. Results from this biomarker analysis contribute to our understanding of which patients may derive greatest benefit from treatment with alisertib and may support our forthcoming clinical studies of alisertib-based therapy in endocrine- and CDK4/6i-resistant metastatic breast cancer."