Paxalisib May Improve Survival in Some With Glioblastoma

Based on the results of a phase 2/3 trial, the manufacturer of paxalisib plans to meet with the FDA.

Results from a phase 2/3 study evaluating paxalisib in patients who were newly diagnosed with glioblastoma were recently announced.

A news release issued by Kazia Therapeutics, the manufacturing company of paxalisib, noted the trial evaluated overall survival (OS; how long patients live, regardless of the cancer’s status) in patients with glioblastoma with unmethylated MGMT promoter status (meaning that the MGMT gene is active). Patients who had recurrent disease (cancer that returned) also were evaluated in the trial.

Glioblastoma is a type of cancer that occurs in the brain or spinal cord, which typically grows quickly and can destroy healthy tissue, as defined by the Mayo Clinic. Although there is not a current cure for glioblastoma, treatments may slow the growth of the cancer and reduce symptoms.

Paxalisib is a type of novel inhibitor that penetrates the blood-brain barrier to treat multiple forms of brain cancer, including glioblastoma, the news release explained. Specifically, the drug works by inhibiting PI3K enzymes, which are activated in many forms of cancer, according to Kazia Therapeutics.

In the trial, 313 patients were randomly assigned to either the paxalisib group or the standard of care group between January 2021 and May 2022. Patients were also enrolled in the standard of care group between July 2019 and May 2022, the news release stated.

During the primary analysis, the median OS was 14.77 months in the group of 54 patients treated with paxalisib, versus 13.84 months in the standard of care group of 75 patients. A prespecified secondary analysis showed that the median OS was 15.54 months, compared with 11.89 months in the paxalisib and standard of care group, respectively, according to the release.

"We are excited to have shown a 3.8-month improvement in overall survival, an approximate 33% improvement, for newly diagnosed unmethylated patients with [glioblastoma] compared to the standard of care [group],” said Dr. John Friend, Kazia Therapeutics’ CEO, in the news release.

Regarding safety, the press release noted that patients tolerated paxalisib well and the trial investigators did not identify any new safety signals in the patient population.

The investigators also did not identify any efficacy signals in the patient population who experienced recurrences, meaning paxalisib and the standard of care treatments were still effective.

Based on the results of the trial, Kazia Therapeutics plans to request a meeting with the Food and Drug Administration (FDA) to discuss the potential for an accelerated approval for paxalisib. The drug was previously granted an orphan drug designation (when a drug shows promise in treating rare diseases or conditions) in February 2018 and fast track designation (speeding up the review of a certain drug) in August 2020 by the FDA. These designations were specifically for patients with glioblastoma in unmethylated MGMT promoter status who previously received radiation plus temozolomide (a type of chemotherapy).

A full presentation of all of the trial’s data is expected to be presented at an upcoming scientific meeting later in the year, the release noted.

“Having comparable Overall Survival data across two independent studies is a compelling outcome in this difficult-to-treat glioblastoma population,” Friend said in the news release. “We look forward to discussing possible approaches for an accelerated approval pathway for paxalisib with the FDA.”

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