Al's Comment:

 The GBM Agile trial is a new style clinical trial that screens multiple treatments against each other at the same time, minimizing the number of patients needed for a control group as each of the arms acts like a control to the other arms.    It does personalize by one biomarker - MGMT methylation status.  Currently, some arms only accept unmethylated patients, but most accept any methylation status.  It uses an algorithm to assign a patient randomly to any arm that patient is qualified for, but it is weighted to assign more patients to the trials doing the best and less to the trials not doing as well.   It quickly can tell if a treatment is worthy of graduating to the next level or not. If not, it is dropped from the rotation and another treatment added.    

Unfortunately for Kazia Therapeutics, it's drug, Paxalisib, which was tested by itself did not do well enough to graduate on, and was dropped from the trial.   This does not mean the end of the drug - it just did not perform well enough by itself in the specified circumstance of newly diagnosed Glioblastoma with unmethylated MGMT and recurrent GBM.  

As I have always been saying, I doubt if the cure is going to be a single magic bullet where a drug will work good enough by itself to cure brain cancer.  Instead, I think a rational combination of drugs will be needed and we need access to these drugs which is impossible (or difficult) under the current regulatory system.  This drug, Paxalisib,  is a PI3K inhibitor.  The PI3K pathway is one of the most important regulators of most cancers.  Unfortunately, targeting this pathway by itself is futile. The cancers that are driven by this pathway just mutate around it and use a different pathway when this is blocked.  However the cancers that were driven by this pathway are weakened when they can't use this pathway, giving other treatments a better chance of working.  There were two presentations about this drug being used in pediatric brain cancers, in combinations.     This was mostly in animal models but they presented two DIPG patients who used the combination of Onc-201 and Paxalisib under compassionate use and both demonstrated dramatic reductions in tumor volume (which is very hard to do with DIPG) and complete resolution of symptoms, with extended overall survival.   The combination is now being tested in a clinical trial.

 I love the concept of the GBM Agile trial, but I do not think we are at the stage where we have effective enough treatments to test.  I think what is needed is our "A Patient-Centric Platform Trial for Precision Oncology" to think up and try combinations that are personalized to each patient.  Our team of experts figures out a list of the best possible treatment options. The patient and their doctor decides which one to try. We try to help get access to it. Then we follow up on each patient to see how it works.  It is like a screening trial of combinations.  When we find a combination that works for a specific scenario, that combination should then be validated ina trial like GBM Agile - they would work together symbiotically.


Posted on: 08/01/2022

Kazia Therapeutics : PROVIDES PROGRESS UPDATE ON GBM AGILE PIVOTAL STUDY

 


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