Country for PR: China
Contributor: PR Newswire Asia (China)
Wednesday, November 18 2020 - 11:16
Kazia Presents Further Paxalisib Data At Sno, Confirming Earlier Positive Safety And Efficacy Signals In Glioblastoma
SYDNEY, Nov. 18, 2020 /PRNewswire-AsiaNet/ --

Kazia Therapeutics Limited (ASX: KZA; NASDAQ: KZIA), an Australian 
oncology-focused biotechnology company, is pleased to share a summary of new 
paxalisib data presented at the Society for Neuro-Oncology (SNO) Annual 
Meeting, which is being held virtually from 19-21 November 2020.

Key Points

- New interim analysis of paxalisib phase II study in glioblastoma 
(NCT03522298) is highly consistent with prior data 
- 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 
- First substantial presentation of safety data at a 60mg dose shows 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 
- Phase I study in DIPG (NCT03696355) shows paediatric maximum tolerated dose 
(MTD) of 27 mg/m2, with safety profile and pharmacokinetics similar to adult 

Kazia CEO, Dr James Garner, commented, "this is very reassuring data from the 
glioblastoma study, confirming our earlier results with the data now much more 
mature. In studies such as this, volatility is the enemy of dependability. From 
the very first efficacy data we reported from this study, in November 2019, 
through the ASCO and AACR 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."

He added, "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."

The poster presentation is available for download via the Kazia website at:-

Summary of Paxalisib Data in Comparison to Temozolomide (existing standard of 

                  Temozolomide[1]                        Paxalisib
                 (FDA-approved treatment)               (interim phase II data)
Progression-Free   5.3 months                           8.4 months
Survival (PFS)
Overall Survival   12.7 months                          17.5 months

Professor Patrick Wen, the first author on the poster, commented "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."

Initial Data from St Jude Study of Paxalisib in DIPG and Diffuse Midline Gliomas

Dr Christopher Tinkle, lead investigator for the SJPI3K study of paxalisib in 
DIPG and diffuse midline glioma (NCT03696355), gave an invited oral 
presentation on interim results from that study.

The SJPI3K study 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.

The study recruited 27 patients, ranging from 3 to 16 years of age. Four 
patients discontinued participation prior to receiving a first dose of 
paxalisib, generally due to disease progression. At the time of analysis, five 
patients remain on paxalisib treatment, and several patients remain in 
post-treatment follow-up.

The paediatric maximum tolerated dose (MTD) was determined to be 27 mg/m2. The 
dose-limiting toxicities (DLTs) included hyperglycaemia, oral mucositis, and 
rash, which are entirely consistent with the adult experience.

The pharmacokinetics of the drug, a term which describes the concentration of 
the drug in plasma over time, was very consistent with the adult experience. 
The study found no meaningful difference between administration of intact 
capsules and administration via opening of capsules and sprinkling of contents 
onto a food carrier.

The study has not at this stage shown a clear survival benefit for paxalisib in 
comparison to historical controls. In terms of PFS, the proportion of patients 
alive and progression-free at six months (PFS6) was 96%, which compares 
favourably to an historical control of 58%[2]. However, the authors note that 
PFS can be a complex endpoint to interpret in DIPG trials due to the 
confounding effect of incidental radiological changes associated with radiation 

Dr Tinkle commented, "my colleagues and I are very pleased with the outcome of 
this study. 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."

He added, "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."

Dr Garner commented, "we are grateful to have had the opportunity to 
collaborate with one of the world's leading paediatric oncology hospitals in 
this study. 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."

Next Steps

The paxalisib phase II study remains ongoing, with final data expected in 1H 
CY2021. The paxalisib arm of the GBM AGILE study has moved into an operational 
phase, and first patient in is expected early in 1Q CY2021.

The St Jude study in DIPG remains ongoing, with final data expected during 1H 

Investor Conference Call

Kazia is pleased to invite investors to attend a conference call to discuss the 
results further. 

The call will be held on Thursday 19 November 2020 at 12:00pm, Sydney time 
(AEDT), which is 5pm on Wednesday 18 November 2020 in San Francisco (PST) and 
8pm on Wednesday 18 November 2020 in New York (EST). 

Participants will need to pre-register for the call via the following link:

Click the 'Register Now' button and follow the prompts to complete 
pre-registration. You will then receive a calendar invite with dial in numbers, 
a passcode and a PIN to dial into the conference call.

[1] ME Hegi, A-C Desirens, T Gorlia, et al. N Engl J Med (2005); 352:997-1003

[2] T Cooney, A Lane, U Bartels, et al. Neuro-Oncology (2017); 19(9):1279-1280

source: Kazia Therapeutics Ltd