First-Line Paxalisib Yields Positive Results in Newly Diagnosed Glioblastoma

Patients with newly diagnosed glioblastoma who were treated with paxalisib saw positive efficacy and safety results.

Paxalisib (GDC-0084) as first line therapy for patients with newly diagnosed glioblastoma achieved positive results in terms of the drug’s safety and efficacy profile, according to a press release on a phase 2 study (NCT03522298) from Kazia Therapeutics Limited.

The median overall survival (OS) in the intent to treat (ITT) population was 15.7 months (95% CI, 11.1-19.1). The finding compares favorably historical findings that have been reported when the same patient population was treated temozolomide, resulting in a median OS of 12.7 months. Patients in the ITT group had a median progression-free survival (PFS) of 8.4 months (95% CI, 6.6-10.2) after being treated paxalisib vs the historical median PFS of 5.3 months among those treated with temozolomide.

“We are pleased to see the phase 2 study of paxalisib successfully completed. [These] data support the inclusion of paxalisib in the [phase 2/3] glioblastoma [GBM] AGILE study [NCT03970447], 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,” principal investigator Patrick Y. Wen, MD, director of the Center for Neuro-Oncology and institute physician at Dana-Farber Cancer Institute, as well as a professor of neurology at Harvard Medical School, said in the press release.

The study was broken into 2 stages, with the first determining an appropriate dose in in the newly diagnosed patients, and the second providing additional information on the efficacy. Investigators also looked to determine overall survival (OS) and progression-free survival (PFS).

A total of 30 patients who had recently diagnosed glioblastoma with an unmethylated O6-methylguaninemethyltransferase (MGMT) promoter status. In the first stage of the study, investigators identified 60 mg once daily as the maximum tolerated dose.

The modified ITT arm included 27 patients who were evaluable for efficacy. Within the population, the median OS had increased to 15.9 months. The safety profile of paxalisib was notably consistent with previously reported clinical trials and included adverse effects such as hyperglycemia, oral mucositis, and skin rash.

The glioblastoma AGILE pivotal study included 7 other trials using paxalisib. By the end of 2021, investigators are expecting 2 other readouts. The final clinical data for the phase 2 trial are expected to be published in the first quarter of 2022.

In August 2020, the FDA granted a fast track designation to paxalisib for patients with newly diagnosed glioblastoma with unmethylated O6-MGMT promoter status after completion of initial radiation with concomitant temozolomide (Temodar).


Kazia announces positive final data from phase II clinical study of paxalisib in newly diagnosed glioblastoma. News Release. Kazia Therapeutics Limited. December 4, 2021. Accessed December 6, 2021.