Tha Nov research might be hard to understand, as to how it could relate to GBM AGILE.
The GBM AGILE trial, talks the talk - in that it is said to be innovative, adaptive, flexible, cutting edge and even more other superlatives.
The easy option is to wait for Overall Survival (OS) results and that would sort out the best new drugs - in comparison with standard of care drugs. But it is understandable, that GBM AGILE want to be "adaptive" and make important decisions - prior to waiting years for OS, plus cost - and patients, that simply don't need to continue in a particular arm. (if substantial evidence supports otherwise)
GBM AGILE have gone to some effort, in this historical study (NOTE: the involvement of the US National Institute and European researchers, in the abstract) - to research or determine, if ORR can be a basis for making these important decisions in GBM AGILE, based on past credible Phase 2 trial results.
GBM AGILE is by far - the premier glioblastoma study happening right now - early important decisions are being made by Patrick Wen and all the others - well I think at least, this timely study is all about their work in GBM AGILE, and the basis of how decisions are being made. (ORR and OS are closely correlated - so "we" are going to use ORR now, pending eventual OS)
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It is easy to get bogged down - but I can't explain it any better
So again to look at the key paragraph below - be tempted to say that the Kazia Phase 2 paxalisib GBM is some sort of benchmark....., or at least some sort of specific example chosen to highlight (over and above the other many dozens of GBM trials).... how poor TMZ control is and the doubling of survival - in comparison.
I don't know - regardless of maybe an incredible coincidence in ref to the 32 patients - Patrick Wen, Tim Clohessy, John DeGroot and Ben Ellingson (and even our stats man) have eliminated temozolomide here, as a viable control. Do investors in this stock now still think paxalisib succumb to TMZ in the GBM study - as exactly how the market reacted to the ASX announcement back in August ?
GBM AGILE is true to its word, I think - in being adaptive enough to close the paxalisib/control study and not take it forward.
So how about Stage 2 results being taken to the FDA. Kazia will have 100 patients in strongly positive OS, verse standard of care .......and its Orphan Drug Designation for glioblastoma granted by the US FDA in February 2018, and a Fast Track Designation for glioblastoma issued by the US FDA in August 2020. In addition, paxalisib was granted Rare Pediatric Disease Designation and
Orphan Designation by the US FDA for DIPG in August 2020.
More than enough for FDA approval - and for GBM AGILE to further explore drugs in other patients, which may in fact, compliment the pathway inhibitor drug paxalisib. Not compete against it.
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"Pooling data from chemotherapy, biologics, and immunotherapy trials, a meta-analysis indicated a strong correlation between ORR and mOS (
R2=0.3164, P< 0.0001; mOS[weeks]=0.6xORR+28.9), suggesting an ORR >20% results in an mOS of > 40.9 weeks, which is double the survival estimate of a treatment with ORR=0% and ≥ 2 months longer than treatments with ORR=5%.
Assuming an ineffective therapy (control) has ORR=5%, a trial of 32 patients with a target ORR=20% leads to the 95% confidence interval higher than the control group. We conclude that single arm phase II studies in recurrent GBM with ≥ 32 patients should have a target ORR ≥ 20%. This was associated with a median OS of approximately 1 year
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Safety, Pharmacokinetics and Efficacy of Paxalisib (GDC …https://clinicaltrials.gov/ct2/show/NCT03522298Web11/5/2018 · This protocol has a
2-part design: This
phase 2 study is an open-label, multicenter, dose-escalation and expansion study to assess the safety, tolerability, …
- Estimated Enrollment : 32 participants
- Study Type : Interventional (Clinical Trial)
