Puma Biotechnology Announces Presentation of Findings from a Phase I/Ib Study of Alisertib in Advanced EGFR-Mutated Lung Cancer

Rhea-AI Summary

Puma Biotechnology (NASDAQ: PBYI) presented findings from a Phase I/Ib study of alisertib in advanced osimertinib-resistant EGFR-mutated non-small cell lung cancer (NSCLC) at the ASCO Annual Meeting. The study, involving 21 patients, found that intermittent dosing of alisertib (30 mg BID) with osimertinib (80 mg daily) was well-tolerated. The overall response rate was 9.5%, and the disease control rate was 81%. Median progression-free survival (PFS) was 5.5 months, and overall survival (OS) was 23.5 months. Notably, TP53 wild type patients showed a higher response rate (25%) and longer PFS (8.0 months) compared to those with TP53 mutations. Adverse events included neutropenia, anemia, diarrhea, and lymphopenia, mostly manageable. The study will now focus on enrolling TP53 wild type patients.

Positive

• Disease control rate of 81% indicates promising efficacy.
• Median overall survival of 23.5 months is encouraging.
• Higher response rate (25%) and PFS (8.0 months) in TP53 wild type patients suggest a targeted benefit.
• Alisertib's combination with osimertinib shows activity against resistant EGFR-mutated NSCLC.

Negative

• Overall response rate is relatively low at 9.5%.
• Progression-free survival for TP53 mutated patients is only 3.7 months.
• Common adverse events include neutropenia (42.9%), anemia (42.9%), and diarrhea (38.1%).
• Grade 3 or higher adverse events reported, including diarrhea (14.3%).

Insights

Financial Analyst

Puma Biotechnology's recent clinical trial results for alisertib in combination with osimertinib present mixed outcomes. The trial showed a median progression-free survival (PFS) of 5.5 months and an overall survival (OS) of 23.5 months, with a distinct difference in efficacy between TP53-mutant and TP53-wild type patients. While these results are influential, especially in a competitive field like oncology, investors should remain cautious. The small sample size of 21 patients limits the generalizability of these findings. Moreover, the trial's adverse event profile, including high incidences of neutropenia and anemia, could pose regulatory hurdles.

From a financial perspective, the focus on TP53-wild type patients may streamline future trials, potentially lowering costs and accelerating time to market. Any future positive data from an expanded patient cohort could significantly enhance Puma's market valuation. However, the current data's limited scope means that substantial investment opportunities may hinge on forthcoming results.

Oncology Doctor

The results from Puma Biotechnology's Phase I/Ib study of alisertib combined with osimertinib offer nuanced insights into its potential efficacy. The trial highlights a median progression-free survival (PFS) of 5.5 months and an overall survival (OS) of 23.5 months for patients with advanced, osimertinib-resistant EGFR-mutated NSCLC. Notably, patients with TP53-wild type tumors had better outcomes compared to those with TP53 mutations, indicating a targeted pathway for future treatments. However, the relatively low overall response rate (9.5%) suggests that alisertib's benefit may be limited to specific patient subsets.

Furthermore, the adverse events, notably neutropenia and anemia, raise concerns about the combination's tolerability. For a treatment to gain broad acceptance, it must exhibit a favorable risk-benefit profile. The decision to modify the trial protocol to focus on TP53-wild type patients is a pragmatic step, potentially maximizing efficacy while minimizing adverse outcomes. Future studies with larger cohorts will be essential to validate these initial findings and determine if the combination can become a viable option in the therapeutic arsenal against EGFR-mutated NSCLC.

Market Research Analyst

The announcement of clinical trial results for alisertib in combination with osimertinib in advanced EGFR-mutated lung cancer is significant for Puma Biotechnology's market positioning. The study’s data, although preliminary, appears to delineate a clear path forward—focusing on TP53-wild type patients who showed more promising outcomes. This strategic pivot could help Puma Biotechnology address a niche yet critical segment within the NSCLC market, currently dominated by osimertinib.

The company's ability to identify and act upon specific biomarkers like TP53 could enhance its competitive edge, particularly as personalized medicine gains traction. Yet, the trial’s small sample size and adverse event profile may dampen immediate market enthusiasm. Long-term, if subsequent trials confirm efficacy with manageable side effects, Puma could carve out a significant share in the NSCLC treatment landscape. Investors should watch for further updates, as these will be pivotal in assessing Puma's potential for sustained market impact.

LOS ANGELES--(BUSINESS WIRE)-- Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, announced the presentation of alisertib for the treatment of patients with advanced osimertinib-resistant epidermal growth factor receptor-mutated (EGFR-mutated) non-small cell lung cancer (NCT04085315) at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting currently being held in Chicago. The poster (Abstract #8572, Poster Bd #436), entitled, “A Phase I/Ib study of the aurora kinase A inhibitor alisertib in combination with osimertinib in advanced osimertinib-resistant EGFR-mutated lung cancer,” was presented by Turja Chakrabarti, MD., University of California, San Francisco, at the Lung Cancer – Non-Small Cell Metastatic Poster Session, on June 3 at 1:30 p.m. CDT. A copy of the poster is available on the Puma website.

This open-label, single-center Phase I/Ib study enrolled 21 evaluable patients with stage IV EGFR-mutated NSCLC (EGFR driver mutation: 76.1% exon 19 deletion; 14.3% L858R; 9.5 % L861Q) who had progressed on osimertinib monotherapy. 47.6% of patients had previously received only first-line osimertinib monotherapy, while 52.3% had received two or greater prior lines of therapy. In the Phase I portion of the trial, 10 patients were treated in a 3+3 dose escalation phase with alisertib using an intermittent dosing strategy of 30 mg (n = 6) or 40 mg (n = 4) twice daily (BID) in combination with osimertinib 80 mg daily. Alisertib was added to osimertinib treatment at the time of disease progression on osimertinib. Intermittent alisertib 30 mg BID was identified as the MTD and RP2D in combination with osimertinib 80 mg daily.

In the Phase Ib expansion portion of the trial, 11 additional patients were treated at the 30 mg alisertib BID intermittent dosing schedule in combination with osimertinib 80 mg daily with alisertib being added to osimertinib treatment at the time of disease progression on osimertinib.

The most common treatment-related adverse events (AEs) (any grade) included neutropenia (42.9%), anemia (42.9%), diarrhea (38.1%), and lymphopenia (33.3%). Grade 3 or higher AEs neutropenia (4.8%), anemia (4.8%), diarrhea (14.3%), and lymphopenia (4.8%).

For the 21 evaluable patients, the investigator assessed overall response rate was 9.5% (95% CI: 0 to 22%) and disease control rate was 81% (95% CI: 69% to 93%). The median PFS for all patients was 5.5 months, while the median OS was 23.5 months. For patients with TP53 mutations (n=9), the overall response rate was 0%, and the disease control rate was 66.7%. For patients who were tp53 wild type (n=8), the overall response rate was 25%, and the disease control rate was 87.5%. For patients with TP53 mutations, the progression free survival was 3.7 months, and for patients who were tp53 wild type, the progression free survival was 8.0 months (hazard ratio:0.42, p = 0.05).

Dr. Collin M. Blakely, the lead principal investigator of the study and senior author of the presentation, from the University of California in San Francisco, said, “We are pleased with the initial results of the clinical trial and very interested in the cohort of patients who are tp53 wild type as tp53 is known to be involved in the aurora kinase pathway. We are modifying the protocol to limit further enrollment in the trial to patients who are tp53 wild type and we look forward to further studying this combination in this biomarker directed cohort of patients.”

Alan H. Auerbach, Chief Executive Officer and President of Puma Biotechnology, said, “We are pleased to see the promising efficacy signals in the cohort of patients who are tp53 wild type. As tp53 is well known to be involved in the aurora kinase pathway, we are pleased to see the activity of alisertib when given in combination with osimertinib in this population of patients. We look forward to continuing to enroll this trial in this cohort of patients.”

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/20240603691086/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 results of Puma Biotechnology's Phase I/Ib study of alisertib in EGFR-mutated NSCLC?

The study showed a disease control rate of 81% and a median overall survival of 23.5 months. The overall response rate was 9.5%.

How did TP53 wild type patients respond to alisertib and osimertinib treatment?

TP53 wild type patients had a 25% response rate and a progression-free survival of 8.0 months.

What were the common adverse events in Puma Biotechnology's alisertib study?

Common adverse events included neutropenia (42.9%), anemia (42.9%), diarrhea (38.1%), and lymphopenia (33.3%).

What is the median progression-free survival for patients in the alisertib study by Puma Biotechnology?

The median progression-free survival was 5.5 months for all patients.

What is the relevance of TP53 mutations in Puma Biotechnology's alisertib study?

Patients with TP53 mutations showed no response and had a progression-free survival of 3.7 months, whereas TP53 wild type patients had better outcomes.