Kazia Therapeutics Limited (ASX:KZA) (NASDAQ:KZIA) will present a summary of new paxalisib data at the Society for Neuro-Oncology Annual Meeting, which is being held virtually from November 19-21, 2020.
The new interim analysis of paxalisib’s Phase II study in glioblastoma (NCT03522298) is highly consistent with prior data, confirming safety and efficacy results.
GBM AGILE pivotal study
Kazia chief executive officer Dr James Garner said: “This is very reassuring data from the glioblastoma study, confirming our earlier results with the data now much more mature.
“From the very first efficacy data we reported from this study, in November 2019, through the ASCO (American Society of Clinical Oncology) and AACR (American Association for Cancer Research) presentations in June 2020, to today’s latest analysis, the PFS and OS figures have remained extremely stable as the study has progressed.
“This gives us a great deal of confidence that what we are seeing is representative and reliable.”
“We expect this study to conclude in the first half of calendar 2021, but it has already provided useful information to guide the development of paxalisib.
“We have moved into the operational phase of the GBM AGILE pivotal study, and we expect that study to now be the primary focus of our work in glioblastoma from this point forward.”
‘Exciting potential candidate’
Professor Patrick Wen, the first author on the poster, added: “As this study has matured, we have seen encouraging results that are very stable over successive analyses, and very consistent with prior clinical experience in this drug.
“Paxalisib is now moving into the GBM AGILE study in glioblastoma, and we expect this to provide definitive data regarding the drug’s potential use in this disease and, if successful, a basis for regulatory approval.
“There remains a profound need for new treatments in glioblastoma, and paxalisib has proven to be an exciting potential candidate.”
Final data expected first half 2021
The paxalisib Phase II study remains ongoing, with final data expected in the first half of 2021.
Kazia said the paxalisib arm of the GBM AGILE study had moved into an operational phase and first patient in was expected early in the first quarter of 2021.
The St Jude study in DIPG remained ongoing, with final data expected during the first half of 2021.
Interim analysis of Phase II study
Median progression-free survival (PFS) of 8.4 months reported on this analysis versus 5.3 months for temozolomide, the existing standard of care.
Median overall survival (OS) of 17.5 months reported versus 12.7 months for temozolomide.
One patient remains progression-free and on treatment 27 months after diagnosis as at August 2020.
The first substantial presentation of safety data at a 60mg dose shows a profile very similar to prior experience, with the most common toxicities including rash, stomatitis (mouth ulcers), and hyperglycemia (high blood sugar), consistent with other PI3K and mTOR inhibitors.
A Phase I study in DIPG (NCT03696355) shows paediatric maximum tolerated dose (MTD) of 27 mg/m2 , with safety profile and pharmacokinetics similar to adult data.
Paxalisib in DIPG and Diffuse Midline Gliomas
The SJPI3K study of paxalisib in DIPG and diffuse midline glioma (NCT03696355), is a first-in-paediatric study, designed to establish the safety and pharmacokinetics of paxalisib in children, and to explore potential early signals of efficacy in this patient population.
Pharmacokinetics of the drug - the concentration of the drug in plasma over time - was very consistent with the adult experience.
The proportion of patients alive and progression-free at six months (PFS6) was 96%, which compares favourably to a historical control of 58%.
Lead investigator Dr Christopher Tinkle said: “We have determined an appropriate dose for future paediatric work, established an acceptable tolerability profile in children, and demonstrated pharmacokinetic equivalence between intact capsule and open and sprinkled administration, which are critical steps in the development of any new drug for paediatric cancer.
”DIPG is an extremely treatment-resistant disease, and no drug has ever shown convincing efficacy as a monotherapy.
“Our view has always been that the treatment of this disease will consist in combination therapy, and we have shown that paxalisib is eminently suitable to now be evaluated alongside other agents.
“We look forward to discussing follow on work that will explore these opportunities and further investigate paxalisib’s potential.”
Kazia’s Dr Garner added: “The results provide an excellent foundation for the further development of paxalisib in DIPG, and we will be excited to discuss the next phase of work with our collaborators in coming months.”