On June 3, 2024 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported 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) (Free ASCO Whitepaper) Annual Meeting currently being held in Chicago (Press release, Puma Biotechnology, JUN 3, 2024, View Source [SID1234644052]). 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.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
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."