Kazia Therapeutics Limited (NASDAQ: KZIA; ASX: KZA), an oncology-focused drug development company, is pleased to announce positive final data from a phase II clinical study of paxalisib as first line therapy in patients with glioblastoma (NCT03522298). The results confirm the previously reported safety and efficacy profile with paxalisib in this high unmet need disease.
Key Points
The study recruited 30 patients with newly diagnosed glioblastoma and unmethylated MGMT promotor status, a genetic profile which confers primary resistance to temozolomide, the only existing FDA-approved drug treatment for first line treatment.
60mg once daily was identified as the maximum tolerated dose (MTD) and selected for future studies.
Median overall survival (OS) in the intent-to-treat (ITT) population (n=30) was 15.7 months (11.1 – 19.1), which compares very favourably to 12.7 months historically reported with temozolomide in this patient group.1
Median progression-free survival (PFS) in the ITT population was 8.4 months (6.6 – 10.2), representing a substantial increment over the comparable figure of 5.3 months associated with temozolomide.
In the modified ITT (mITT) population (n=27), which includes only those patients evaluable for efficacy, OS increased to 15.9 months (12.8 – 19.1).
The safety profile of paxalisib was highly consistent with previous clinical studies: hyperglycaemia, oral mucositis, and skin rash were among the most common drug-related toxicities.
Kazia expects to receive a final clinical study report in 1Q CY2022 and intends to seek publication of these data in a peer-reviewed scientific journal thereafter.
Kazia CEO, Dr James Garner, commented, "We are delighted to report positive final data from the completed phase II study of paxalisib. The data continue to demonstrate a clear efficacy signal and favourable safety profile, suggesting a meaningful advantage over temozolomide, the existing standard of care, and validating our decision last year to join the GBM AGILE pivotal study. We have gleaned invaluable insights from this trial, and we are tremendously grateful to the investigators and to the patients who participated. Our task now, as we move rapidly toward a potential marketing authorization, is to confirm and quantify the benefit associated with paxalisib in glioblastoma patients. This indeed is the focus of our participation in GBM AGILE, which commenced recruiting to the paxalisib arm in January 2021. We are increasingly also exploring additional patient populations for which a brain penetrant PI3K/mTOR inhibitor may provide significant advantages over the standard of care."
Professor Patrick Wen, Principal Investigator at Dana Farber Cancer Institute, commented "We are pleased to see the phase II study of paxalisib successfully completed. This data supports the inclusion of paxalisib in the GBM AGILE study, which has recently expanded to Canada. Glioblastoma remains a disease in urgent need of new therapeutic options, and we look forward to seeing further data for paxalisib from GBM AGILE in due course."
Clinical Trial Design
The phase II study of paxalisib was an adaptive trial, conducted in two stages. The first stage sought to determine the most appropriate dose in newly diagnosed patients. The second stage was intended to provide additional information on dosing and to seek a preliminary efficacy signal in order to de-risk transition to a larger, pivotal study.
Consistent with these objectives, the primary objective of the study was to evaluate the safety and tolerability of paxalisib in patients with newly diagnosed glioblastoma. The secondary objectives included typical pharmacokinetic parameters, and efficacy endpoints including overall survival (OS) and progression-free survival (PFS).
The phase II study was conducted in 30 patients at six centres in the United States. It was a single ar...
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