Puma Biotechnology Announces Presentation of Findings from a Phase II Study of Alisertib in Endocrine-Resistant Metastatic Breast Cancer (TBCRC 041)

Rhea-AI Summary

Puma Biotechnology (NASDAQ: PBYI) presented promising findings from a Phase II study of alisertib for endocrine and CDK4/6 inhibitor-resistant, HER2-negative, hormone receptor-positive metastatic breast cancer at the 2024 ASCO Annual Meeting.

The study compared alisertib alone versus alisertib plus fulvestrant, showing overall response rates of 19.6% and 20.0%, respectively. Median progression-free survival was 5.6 months for alisertib and 5.4 months for the combination therapy, both indicating tolerable safety profiles.

Key biomarker findings include decreased progression-free survival in patients with PIK3CA mutations and longer progression-free survival associated with lower circulating tumor cell counts and lower methylated tumor fraction percentages. Ongoing analyses aim to identify patients who may benefit most from alisertib.

Positive

• Promising overall response rates: 19.6% for alisertib and 20.0% for alisertib + fulvestrant.
• Median progression-free survival: 5.6 months for alisertib and 5.4 months for alisertib + fulvestrant.
• Tolerable safety profile for both treatment arms.
• Lower circulating tumor cells associated with longer progression-free survival (7.4 months vs. 4.5 months, HR=1.8; p=0.018).
• Longer progression-free survival linked to lower methylated tumor fraction percentages (11.5 months vs. 3.2 months, HR 3.0; p<0.001).

Negative

• Patients with PIK3CA mutations experienced decreased progression-free survival (HR 1.8; p=0.0225).
• No significant impact on progression-free survival for patients with ESR1 mutations (p=0.594).

Insights

Medical Research Analyst

The Phase II study's findings on alisertib in endocrine-resistant metastatic breast cancer offer new insights into the drug's clinical activity and safety profile. Despite the modest overall response rate (approximately 20% in both arms), the tolerable safety profile makes it a potential option for this challenging patient population.

Key biomarker findings, such as the impact of PIK3CA and ESR1 mutations on progression-free survival (PFS), are noteworthy. Patients with PIK3CA mutations experienced decreased PFS, highlighting the importance of genetic profiling in treatment planning. The lower PFS associated with higher circulating tumor cells (CTCs) and methylated tumor fraction (mTF) further underscores the potential utility of liquid biopsies in monitoring disease progression and tailoring therapy.

While the study's results are promising, the modest efficacy signals and need for ongoing biomarker analyses suggest that alisertib's role in this setting remains to be fully defined. Investors should watch for future trials that may refine patient selection and improve outcomes.

Market Research Analyst

The announcement of Puma Biotechnology's Phase II trial results could have positive implications for the company's stock, as it reinforces their commitment to addressing unmet needs in endocrine-resistant metastatic breast cancer. The focus on biomarker-driven research is consistent with industry trends, aligning with precision medicine initiatives that aim to optimize treatment effectiveness.

However, it's important to note the relatively modest improvements in response rate and progression-free survival. While the safety profile is favorable, which is important for long-term market acceptance, the efficacy data indicates that alisertib may need to be combined with other therapeutic agents to achieve more substantial benefits.

Retail investors should consider the broader competitive landscape, including other emerging therapies targeting similar patient populations. The ongoing biomarker analysis and potential future trials represent both an opportunity for breakthroughs and a risk of delayed market entry if additional studies are needed.

LOS ANGELES--(BUSINESS WIRE)-- Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, announced 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) Annual Meeting currently being held in Chicago. 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.

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.”

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 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 U.S. 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/20240602354785/en/

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

info@pumabiotechnology.com

ir@pumabiotechnology.com



David Schull or Olipriya Das, Russo Partners, +1 212 845 4200

david.schull@russopartnersllc.com

olipriya.das@russopartnersllc.com

Source: Puma Biotechnology, Inc.

FAQ

What were the overall response rates in the Phase II study of alisertib for endocrine-resistant metastatic breast cancer?

The overall response rates were 19.6% for alisertib alone and 20.0% for alisertib plus fulvestrant.

What is the median progression-free survival reported in the Phase II study of alisertib?

The median progression-free survival was 5.6 months for alisertib and 5.4 months for alisertib plus fulvestrant.

How did PIK3CA mutations affect progression-free survival in the Phase II study of alisertib?

Patients with PIK3CA mutations experienced decreased progression-free survival (HR 1.8; p=0.0225).

Were there any significant findings related to circulating tumor cells in the Phase II study of alisertib?

Yes, lower circulating tumor cell counts were associated with longer progression-free survival (7.4 months vs. 4.5 months, HR=1.8; p=0.018).

What impact did methylated tumor fraction percentages have on progression-free survival in the Phase II study of alisertib?

Lower methylated tumor fraction percentages were associated with longer progression-free survival (11.5 months vs. 3.2 months, HR 3.0; p<0.001).