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  • ||||||||||  paxalisib (GDC-0084) / Kazia, SoVarGen, QIMR Berghofer Medical Research Institute
    Journal, IO biomarker:  Depleting the action of EZH2 through PI3K-mTOR inhibition to overcome metastasis and immunotherapy resistance in triple-negative breast cancer. (Pubmed Central) -  Jun 11, 2025   
    Dual PI3K-mTOR inhibition with paxalisib not only promotes a favorable mesenchymal to epithelial phenotype but also inhibits signatures associated with MICs, including the highly aggressive CSC phenotype, persister cancer cell phenotype (p65, FOXQ1, NRF2, NNMT), and a cancer drug resistance signature (ABCB5, SNAIL, ALDH1)...PI3K-mTOR blockade acts upstream of EZH2, impacting both the classical repressive catalytic p85?-EZH2-H27ME3 and active EZH2-NF?B pathways. Our data suggest that dual targeting of the PI3K-mTOR pathway disrupts both the catalytic and non-catalytic axes of EZH2 to inhibit metastasis and enhance cancer immune visibility, potentially increasing the utility of immunotherapy in resistant individuals.
  • ||||||||||  paxalisib (GDC-0084) / Kazia, SoVarGen, QIMR Berghofer Medical Research Institute, dordaviprone (ONC201) / Jazz
    The gut microbiome in pediatric diffuse midline gliomas: Correlative study results from the PNOC022 trial. (S504) -  Apr 23, 2025 - Abstract #ASCO2025ASCO_3146;    
    Our data suggest that dual targeting of the PI3K-mTOR pathway disrupts both the catalytic and non-catalytic axes of EZH2 to inhibit metastasis and enhance cancer immune visibility, potentially increasing the utility of immunotherapy in resistant individuals. This report focuses on the combination therapy arm involving dordaviprone and paxalisib, administered to patients (aged 2
  • ||||||||||  paxalisib (GDC-0084) / Kazia, SoVarGen, QIMR Berghofer Medical Research Institute
    Trial completion date, Trial primary completion date:  GDC-0084 With Radiation Therapy for People With PIK3CA-Mutated Solid Tumor Brain Metastases or Leptomeningeal Metastases (clinicaltrials.gov) -  Apr 17, 2025   
    P1,  N=21, Active, not recruiting, 
    This report focuses on the combination therapy arm involving dordaviprone and paxalisib, administered to patients (aged 2 Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026
  • ||||||||||  SNV1521 / Synnovation Therap
    Enrollment change:  SNV1521-101: SNV1521 in Participants with Advanced Solid Tumors (clinicaltrials.gov) -  Mar 13, 2025   
    P1,  N=200, Recruiting, 
    In addition, Metformin, ME-344 and NV-128 may be therapeutic agents for AAA by regulating the cuproptosis. N=76 --> 200
  • ||||||||||  NV-128 / MEI
    ME128 - How to apply organoid models to study infectious disease (Hall 14) -  Feb 1, 2025 - Abstract #ESCMIDGlobal2025ESCMID_Global_790;    
    These tools offer exciting insights into host-pathogen interactions and therapeutic applications at a molecular level. In this MTE, both the application of organoid models in molecular biology and their clinical use to study and combat infectious diseases, including their potential to advance personalised medicine, will be presented.
  • ||||||||||  Trial completion date, Trial primary completion date:  Genetic Testing in Guiding Treatment for Patients With Brain Metastases (clinicaltrials.gov) -  Jan 15, 2025   
    P2,  N=186, Recruiting, 
    In this MTE, both the application of organoid models in molecular biology and their clinical use to study and combat infectious diseases, including their potential to advance personalised medicine, will be presented. Trial completion date: Jun 2026 --> Jun 2028 | Trial primary completion date: Oct 2025 --> Oct 2026
  • ||||||||||  Trial completion date, Trial primary completion date:  Genetic Testing in Guiding Treatment for Patients With Brain Metastases (clinicaltrials.gov) -  Dec 27, 2024   
    P2,  N=186, Recruiting, 
    Trial completion date: Jun 2026 --> Jun 2028 | Trial primary completion date: Oct 2025 --> Oct 2026 Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Oct 2024 --> Oct 2025
  • ||||||||||  riluzole / Generic mfg., NV-128 / MEI, ME-344 / MEI
    Journal:  Correlation of disulfidptosis and periodontitis: New insights and clinical significance. (Pubmed Central) -  Jul 28, 2024   
    This work lays the groundwork for novel anthocyanin production by a process involving the placement of several biosynthesis genes under the control of a gene cluster. SLC7A11, SLC3A2, RPN1, NCKAP1, LRPPRC, and NDUFS1 are targets associated with disulfidptosis in periodontitis, and ME-344, NV-128, and RILUZOLE are promising agents for the treatment of periodontitis.
  • ||||||||||  paxalisib (GDC-0084) / Kazia, SoVarGen, pimasertib (AS703026) / Day One Biopharma
    Enrollment open, Trial initiation date:  Optimal Precision TherapIes to CustoMISE Care in Childhood and Adolescent Cancer (clinicaltrials.gov) -  Jul 11, 2024   
    P1/2,  N=82, Recruiting, 
    SLC7A11, SLC3A2, RPN1, NCKAP1, LRPPRC, and NDUFS1 are targets associated with disulfidptosis in periodontitis, and ME-344, NV-128, and RILUZOLE are promising agents for the treatment of periodontitis. Not yet recruiting --> Recruiting | Initiation date: Mar 2024 --> Jul 2024
  • ||||||||||  paxalisib (GDC-0084) / Kazia, SoVarGen, QIMR Berghofer Medical Research Institute, dordaviprone (ONC201) / Jazz
    Phase classification:  PNOC022: Combination Therapy for the Treatment of Diffuse Midline Gliomas (clinicaltrials.gov) -  Jun 12, 2024   
    P2,  N=360, Recruiting, 
    Recruiting --> Active, not recruiting | N=60 --> 32 Phase classification: P1/2 --> P2
  • ||||||||||  paxalisib (GDC-0084) / Kazia, SoVarGen, QIMR Berghofer Medical Research Institute, dordaviprone (ONC201) / Jazz
    Phase classification, Trial completion date:  PNOC022: Combination Therapy for the Treatment of Diffuse Midline Gliomas (clinicaltrials.gov) -  Jun 10, 2024   
    P1/2,  N=360, Recruiting, 
    Phase classification: P1/2 --> P2 Phase classification: P2 --> P1/2 | Trial completion date: Jun 2027 --> Jun 2029
  • ||||||||||  paxalisib (GDC-0084) / Kazia, SoVarGen
    Trial completion date, Trial primary completion date:  Paxalisib (GDC-0084) In Recurrent Or Refractory PCNSL (clinicaltrials.gov) -  May 20, 2024   
    P2,  N=25, Recruiting, 
    Phase classification: P2 --> P1/2 | Trial completion date: Jun 2027 --> Jun 2029 Trial completion date: May 2025 --> Dec 2026 | Trial primary completion date: May 2024 --> Dec 2025
  • ||||||||||  paxalisib (GDC-0084) / Kazia, SoVarGen, QIMR Berghofer Medical Research Institute, dordaviprone (ONC201) / Jazz
    Enrollment open, Enrollment change:  PNOC022: Combination Therapy for the Treatment of Diffuse Midline Gliomas (clinicaltrials.gov) -  May 9, 2024   
    P2,  N=324, Recruiting, 
    Trial completion date: May 2025 --> Dec 2026 | Trial primary completion date: May 2024 --> Dec 2025 Active, not recruiting --> Recruiting | N=143 --> 324
  • ||||||||||  SNV1521 / Synnovation Therap
    Enrollment open:  SNV1521-101: SNV1521 in Participants with Advanced Solid Tumors (clinicaltrials.gov) -  May 3, 2024   
    P1,  N=76, Recruiting, 
    Active, not recruiting --> Recruiting | N=143 --> 324 Not yet recruiting --> Recruiting
  • ||||||||||  metformin / Generic mfg.
    Journal:  Just a spoonful of metformin helps the medicine go down. (Pubmed Central) -  Mar 19, 2024   
    To tackle this mechanism of resistance, the authors added the PKC inhibitor enzastaurin to their drug combination and showed that this triple therapy led to improved survival. This approach paves the way for improved outcomes for patients with DIPG and other brain tumors.
  • ||||||||||  Kinenza (enzastaurin) / Denovo, Aytu BioPharma, paxalisib (GDC-0084) / Kazia
    Journal:  PI3K/mTOR is a therapeutically targetable genetic dependency in diffuse intrinsic pontine glioma. (Pubmed Central) -  Mar 18, 2024   
    Therapeutic adaptation was assessed using spatial transcriptomics and ATAC-sequencing, identifying changes in myelination and tumor immune microenvironment crosstalk. Together, we have identified a clinically relevant DIPG therapeutic combinatorial approach.
  • ||||||||||  EVT801 / Evotec, Kazia
    Biomarkers analysis on samples from patients in EVT801 clinical trial: Patient characterization and immunomonitoring (Section 43) -  Mar 5, 2024 - Abstract #AACR2024AACR_2338;    
    P1
    VEGFR3 expression also tends to be correlated with higher levels of hypoxia (CAIX labelling). Our working hypothesis is that patients with hypoxic HGS-OC tumors with high VEGFR3 expression may benefit from EVT801 treatment; this will need to be reinforced by inclusion of additional patients in dedicated PD biomarkers cohorts during stage 2 of the clinical trial.
  • ||||||||||  paxalisib (GDC-0084) / Kazia, dordaviprone (ONC201) / Chimerix
    Journal:  Rational combination platform trial design for children and young adults with Diffuse Midline Glioma: a report from PNOC. (Pubmed Central) -  Dec 21, 2023   
    P2
    This combination treatment aimed at inducing metabolic distress led to the design of the first DMG-specific platform trial PNOC022 (NCT05009992). Here, we expand on the PNOC022 rationale and discuss various considerations, including liquid biome, microbiome, and genomic biomarkers, quality-of-life endpoints, and novel imaging modalities, such that we offer direction on future clinical trials in DMG.
  • ||||||||||  Trial completion date, Trial primary completion date:  GBM AGILE: A Trial to Evaluate Multiple Regimens in Newly Diagnosed and Recurrent Glioblastoma (clinicaltrials.gov) -  Dec 1, 2023   
    P2/3,  N=1030, Recruiting, 
    Here, we expand on the PNOC022 rationale and discuss various considerations, including liquid biome, microbiome, and genomic biomarkers, quality-of-life endpoints, and novel imaging modalities, such that we offer direction on future clinical trials in DMG. .
  • ||||||||||  paxalisib (GDC-0084) / Kazia, SoVarGen, QIMR Berghofer Medical Research Institute, dordaviprone (ONC201) / Jazz
    Enrollment closed, Enrollment change:  PNOC022: Combination Therapy for the Treatment of Diffuse Midline Gliomas (clinicaltrials.gov) -  Nov 26, 2023   
    P2,  N=143, Active, not recruiting, 
    . Recruiting --> Active, not recruiting | N=324 --> 143
  • ||||||||||  Kinenza (enzastaurin) / Denovo, Aytu BioPharma, paxalisib (GDC-0084) / Kazia
    Exploiting the genetic dependency on PI3K/mTOR signaling for the treatment of H3-altered diffuse midline glioma (Room 121-122) -  Nov 11, 2023 - Abstract #SNO2023SNO_276;    
    P1, P2
    Mechanisms of adaptation/plasticity were assessed by ATAC-Seq and quantitative proteomic profiling xenograft tumors refractory to treatment. Here we address the intrinsic neoplastic sequela of DIPG, by combined targeting of PI3K/Akt/mTOR using paxalisib, compensatory PKC signaling using enzastaurin, coupled with strategies to manage treatment-related side-effects and reduced efficacy using metformin; providing the preclinical rationale for the addition of metformin to NCT05009992.
  • ||||||||||  paxalisib (GDC-0084) / Kazia, SoVarGen
    Trial completion date, Trial primary completion date:  Paxalisib With a High Fat, Low Carb Diet and Metformin for Glioblastoma (clinicaltrials.gov) -  Sep 26, 2023   
    P2,  N=33, Recruiting, 
    These data inform the phase II clinical trial (NCT05009992). Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2024
  • ||||||||||  paxalisib (GDC-0084) / Kazia, SoVarGen
    Trial completion date, Trial primary completion date:  Paxalisib (GDC-0084) In Recurrent Or Refractory PCNSL (clinicaltrials.gov) -  Jul 5, 2023   
    P2,  N=25, Recruiting, 
    Accordingly, VEGFR-3 expression is retrospectively quantified during the EVT801 phase 1 clinical trial and may be used to stratify patients in the future. Trial completion date: May 2024 --> May 2025 | Trial primary completion date: May 2023 --> May 2024
  • ||||||||||  paxalisib (GDC-0084) / Kazia, dordaviprone (ONC201) / Chimerix
    Journal, Combination therapy:  ONC201 in Combination with Paxalisib for the Treatment of H3K27-Altered Diffuse Midline Glioma. (Pubmed Central) -  May 17, 2023   
    P2
    Together, these discoveries coupled with the powerful anti-DIPG/DMG pharmacokinetic and pharmacodynamic properties of ONC201 and paxalisib have provided the rationale for the ongoing DIPG/DMG phase II combination clinical trial NCT05009992. PI3K/Akt signaling promotes metabolic adaptation to ONC201-mediated disruption of mitochondrial energy homeostasis in diffuse intrinsic pontine glioma, highlighting the utility of a combination treatment strategy using ONC201 and the PI3K/Akt inhibitor paxalisib.