Paxalisib Shows Positive Survival Data in Glioblastoma

Treatment with paxalisib, an investigational small molecule inhibitor of the PI3K/AKT/mTOR pathway, was associated with a positive overall survival signal in patients with glioblastoma.

Treatment with paxalisib (formerly GDC-0084), an investigational small molecule inhibitor of the PI3K/AKT/mTOR pathway, was associated with a positive overall survival (OS) signal in patients with glioblastoma, according to interim data from an ongoing phase II study.

In a small 9-patient subgroup, the median OS was 17.7 months with paxalisib, which compares favorably with the 12.7-month OS demonstrated in this setting with the approved standard of care, temozolomide. Among a slightly larger subgroup of 30 patients, the median progression-free survival (PFS) was 8.5 months, which again compares favorably with the demonstrated median PFS with temozolomide of 5.3 months in this setting.

Kazia Therapeutics Limited, the manufacturer of paxalisib, emphasized in a press release that, “Comparison between different studies is always imprecise,” but added that, “The magnitude of the numerical difference provides powerful evidence that treatment with paxalisib may extend life in this patient group.”

Commenting on the data in the press release, Kazia CEO, James Garner, James Garner, MA, MBA, MBBS, BSC (Hons), MAICD, said , "The 'gold standard' for any new cancer treatment is the ability to extend life—an especially challenging goal in a disease such as glioblastoma—and this data provides our first evidence that paxalisib may achieve this objective in a very challenging patient population.

"There have not been any new drug treatments for newly-diagnosed glioblastoma patients for over twenty years, and we aspire to change that situation...The study continues to follow a number of patients who remain on treatment, and we currently expect to report a further data read-out in the second half of the year."

Overall, the study enrolled 30 patients, 9 patients in Part A, a dose-escalation cohort, and an additional 21 patients in Part B. The OS analysis included only the 9 patients from Part A, while the PFS analysis included all 30 evaluable patients from Parts A and B.

In the press release, Kazia noted that the OS and PFS data the company reported are “provisional” and “may change as ongoing patients proceed through the study.”

The patient who has received treatment for the longest period, remains progression-free 19 months’ post-diagnosis. About half of the enrolled patients remain on treatment.

Regarding toxicity, there were no major safety issues, with hyperglycaemia, oral mucositis, and low-grade rash among the most frequently reported adverse-events related to the treatment.

Kazia anticipates reporting additional data later this year and final results in the first half of next year. Beyond this phase II study 4 other ongoing studies are exploring paxalisib in patients with different types of brain cancer.

These findings had been scheduled for live presentation at the 2020 AACR Annual Meeting, which was scheduled to take place in San Diego, from April 24 to 29; however, the live meeting was cancelled due to the COVID-19 crisis. Thus, Kazia decided to report these data now.

Kazia's Paxalisib Shows Positive Overall Survival Signal in Phase II Glioblastoma Study. Published April 7, 2020. Accessed April 7, 2020.