Paxalisib to Dominate Forum, page-5

Sabine Mueller (Zurich & UCLA) Javad Nazarian absolute world experts - Sabine head of that Paxalisib DIPG Clinical trial with 2 other drugs.

New very recent research - say they can real time test DIPG drugs. The "other 2 drugs" not mentioned, only Paxalisib.

Pre release of results of the trial - they need to be selective with wording, otherwise it could result in massive on market buying of Kazia shares. Millions of shares traded, resulting in a dramatic SP upward movement.  (No just sarcasm, from this disappointed KZA investor). Nevertheless - this trial started in 2021 and a very positive Paxalisib snippet here, from about 10 weeks ago.


Real-time drug testing of paediatric diffuse midline glioma to support clinical decision making: The Zurich DIPG/DMG centre experience

• Javad Nazarian ²
• Sabine Mueller ²
  

Published:November 28, 2022DOI:https://doi.org/10.1016/j.ejca.2022.10.014


Highlights

• •
  Robot-assisted brainstem biopsy for pontine diffuse midline gliomas (DMG) is feasible and safe.
• •
  Real-time drug testing on patient-derived DMG cells define individualised treatments.
• •
  Targeted agents as paxalisib can be successfully integrated into the care of DMG.

Abstract

Background

Children diagnosed with diffuse midline gliomas (DMG) have an extremely poor overall survival: 9–12 months from diagnosis with currently no curative treatment options. Given DMG molecular heterogeneity, surgical biopsies are needed for molecular profiling and as part of enrolment into molecular-based and precision medicine type clinical interventions. In this study, we describe the results of real time profiling and drug testing at the diffuse intrinsic pontine glioma/DMG Research Centre at University Children's Hospital Zurich.
Method

Biopsies were taken using a frame based stereotactic robot system (NeuroMate®, Renishaw) at University Children's Hospital Zurich. Tissue samples were evaluated to confirm diagnosis by H3K27M and H3K27 trimethylation loss. Genomic analyses were done using a variety of platforms (INFORM, Oncomine, UCSF500 gene panel).

Cell lines were developed by mechanical tissue dissociation and verified by either sequencing or immunofluorescence staining confirming H3K27M mutation and used afterwards for drug testing.
Results

Twenty-five robot-assisted primary biopsies were successfully performed. Median hospital stay was 2 days (range 1–4 days). Nine low-passage patient-derived cells were developed, whereas 8 cell lines were used to inform response to clinically relevant drugs. Genome and RNA expression were used to further guide treatment strategies with targeted agents such as dual PI3K/mTOR inhibitor paxalisib.
Conclusion

We established a systematic workflow for safe, robot-assisted brainstem biopsies and in-house tissue processing, followed by real-time drug testing. This provides valuable insights into tumour prognostic and individual treatment strategies targeting relevant vulnerabilities in these tumours in a clinically meaningful time frame.






Sabine Mueller, MD Ph.D. MAS serves as the Head of the Clinical Program of the DIPG/DMG . She also leads the Pediatric Brain Tumor Program at UCSF and the Pacific Pediatric Neuro-Oncology Consortium (www.pnoc.us)

Javad Nazarian, Prof. Ph.D. serves as the Head of the Translational Program of the DIPG/DMG Center Zurich