Puma Biotech Presents Phase I/Ib Alisertib Study Results in Advanced EGFR-Mutated Lung Cancer

Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical firm, has revealed promising data on alisertib for patients with advanced osimertinib-resistant, epidermal growth factor receptor-mutated (EGFR-mutated) non-small cell lung cancer (NSCLC). The findings were showcased at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. The study, titled “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 Dr. Turja Chakrabarti from the University of California, San Francisco.

The open-label, single-center Phase I/Ib study included 21 evaluable patients with stage IV EGFR-mutated NSCLC. These patients had previously shown progression on osimertinib monotherapy. Of the participants, 47.6% had only received first-line osimertinib, while 52.3% had undergone two or more prior therapies. In the initial Phase I portion, 10 patients underwent a dose-escalation phase using alisertib in combination with osimertinib, aiming to identify the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). The study determined that an intermittent dose of 30 mg alisertib twice daily (BID) combined with 80 mg osimertinib daily was the MTD and RP2D.

In the subsequent Phase Ib expansion, an additional 11 patients were treated with the identified dosing schedule. The adverse events (AEs) most frequently observed included neutropenia (42.9%), anemia (42.9%), diarrhea (38.1%), and lymphopenia (33.3%). Severe AEs (Grade 3 or higher) were neutropenia (4.8%), anemia (4.8%), diarrhea (14.3%), and lymphopenia (4.8%).

For the 21 evaluable patients, the overall response rate assessed by investigators was 9.5%, while the disease control rate stood at 81%. The median progression-free survival (PFS) was 5.5 months, and the median overall survival (OS) was 23.5 months. When breaking down the data, patients with TP53 mutations exhibited an overall response rate of 0% and a disease control rate of 66.7%, with a PFS of 3.7 months. Conversely, TP53 wild-type patients had a 25% overall response rate and an 87.5% disease control rate, with a PFS of 8.0 months.

Dr. Collin M. Blakely, the lead principal investigator of the study, expressed satisfaction with the preliminary results and highlighted the interest in TP53 wild-type patients, given TP53's role in the aurora kinase pathway. Consequently, the trial protocol is being adjusted to focus on this patient subgroup.

Alan H. Auerbach, CEO and President of Puma Biotechnology, echoed Dr. Blakely's sentiments, emphasizing the promising efficacy signals observed in TP53 wild-type patients. He noted the importance of TP53 in the aurora kinase pathway and expressed eagerness to continue exploring alisertib's potential in combination with osimertinib for this specific patient population.

Puma Biotechnology, Inc. specializes in developing and commercializing innovative products aimed at enhancing cancer treatment. The company licensed global rights to PB272 (neratinib) in 2011, which received FDA approval in 2017 for the extended adjuvant treatment of early-stage HER2-positive breast cancer. Additionally, in February 2020, neratinib was approved for use with capecitabine in treating advanced HER2-positive breast cancer. Puma also holds an exclusive license for alisertib, an investigational inhibitor of aurora kinase A, with plans to develop it for small cell lung cancer and breast cancer. In February 2024, Puma initiated ALISCA-Lung 1, a Phase II trial of alisertib monotherapy for extensive-stage small cell lung cancer.

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