Kazia Therapeutics Reports Phase II/III Paxalisib Results in Glioblastoma

Kazia Therapeutics Limited, an oncology-focused drug development company, has unveiled promising results from the GBM AGILE study, a Phase II/III global trial. This trial assessed the efficacy of paxalisib, a potential therapeutic for glioblastoma, a severe brain cancer with limited treatment options. Glioblastoma, especially in patients with unmethylated MGMT promoter status, remains a challenging condition, necessitating innovative treatments.

The GBM AGILE study, spearheaded by the Global Coalition for Adaptive Research (GCAR), incorporated a sophisticated adaptive trial design. This method employed Bayesian principles to compare the overall survival (OS) of patients treated with investigational agents against those receiving the standard of care (SOC). The trial included institutions like Memorial Sloan Kettering Cancer Center and Dana-Farber Cancer Institute, bringing together top clinical and scientific expertise.

Kazia's investigational drug, paxalisib, was the third candidate examined in the trial. The study focused on newly diagnosed glioblastoma patients with unmethylated MGMT promoter status and those with recurrent disease. Notably, paxalisib showed a significant improvement in overall survival for newly diagnosed unmethylated (NDU) patients compared to the SOC treatment.

Kazia's CEO, Dr. John Friend, expressed optimism regarding the results, highlighting a 3.8-month improvement in overall survival for NDU patients treated with paxalisib. This represents a 33% enhancement compared to the concurrent SOC group. The company aims to explore accelerated approval pathways for paxalisib with the U.S. Food and Drug Administration (FDA).

In the study, 313 patients, both newly diagnosed and recurrent, were randomized to receive either paxalisib or the SOC treatment from January 2021 to May 2022. The control group data was collected from July 2019, the study's initiation, until May 2022.

In the primary analysis, the median OS for paxalisib-treated NDU patients was 14.77 months, compared to 13.84 months for the cumulative SOC patients. A more detailed secondary analysis revealed that the median OS for paxalisib patients was 15.54 months, in contrast to 11.89 months for those on concurrent SOC. A sensitivity analysis corroborated these findings, showing a similar median OS difference.

These results align with earlier data from a Company-sponsored phase II study, where paxalisib demonstrated a median OS of 15.7 months for NDU patients, compared to 12.7 months historically reported for temozolomide. Moreover, paxalisib was well-tolerated, and no new safety concerns emerged during the trial.

However, the study did not detect an efficacy signal in the recurrent disease population, with median OS of 9.69 months for SOC and 8.05 months for paxalisib. Similar outcomes were observed for other drug candidates in the GBM AGILE trial. Kazia is conducting further analyses to understand these findings better.

Kazia plans to seek a meeting with the FDA, leveraging the comprehensive data from all paxalisib clinical studies to discuss potential accelerated approval. Paxalisib has previously received orphan drug designation and fast track designation from the FDA for glioblastoma in unmethylated MGMT promoter status patients, following radiation plus temozolomide therapy.

The company anticipates presenting the full data, including secondary endpoints from the GBM AGILE study, at a scientific meeting later this year. Kazia Therapeutics continues its mission to develop innovative therapies for brain cancer, with paxalisib at the forefront of its efforts, supported by ongoing trials in various forms of brain cancer.

In addition to paxalisib, Kazia is also developing EVT801, a small-molecule inhibitor of VEGFR3, licensed from Evotec SE. Preclinical data suggests EVT801 is effective against a range of tumors and may work synergistically with immuno-oncology agents. A Phase I study for EVT801 is currently underway, with preliminary data expected to be presented in 2024.