- |||||||||| paxalisib (GDC-0084) / Kazia, SoVarGen
Enrollment closed, Enrollment change: Safety, Pharmacokinetics and Efficacy of Paxalisib (GDC-0084) in Newly-diagnosed Glioblastoma (clinicaltrials.gov) - Mar 11, 2020 P2, N=32, Active, not recruiting, Recruiting --> Active, not recruiting Recruiting --> Active, not recruiting | N=66 --> 32
- |||||||||| Rozlytrek (entrectinib) / Roche, paxalisib (GDC-0084) / Kazia, Verzenio (abemaciclib) / Eli Lilly
[VIRTUAL] Alliance A071701: Genomically guided treatment trial in brain metastases. (Poster Board 64) - Feb 27, 2020 - Abstract #ASCO2020ASCO_232; P2 This study represents a novel individualized therapeutic approach in brain metastases, a disease with a critical need for effective therapy. Research Funding: U.S. National Institutes of Health, Pharmaceutical/Biotech Company, U.S. National Institutes of Health
- |||||||||| GDC-0084 / Kazia
Clinical, Journal: An LC/ESI-MS/MS method to quantify the PI3K inhibitor GDC-0084 in human plasma and cerebrospinal fluid: validation and clinical application. (Pubmed Central) - Jan 24, 2020 The lower limit of quantitation and limit of detection for GDC-0084 in human plasma were 0.2 ng/mL (signal/noise ≥ 47) and 0.005 ng/mL (signal/noise ≥ 3.5), respectively, and for GDC-0084 in human CSF were 0.2 ng/mL (signal/noise ≥ 19.7) and 0.04 ng/mL (signal/noise ≥ 7.2). This method was successfully applied to analyze serial plasma samples obtained from children with diffuse intrinsic pontine gliomas and other midline gliomas who participated in pharmacokinetic studies as part of a phase I clinical trial of GDC-0084.
- |||||||||| GDC-0084 / Kazia
Multi-parametric MR-PET imaging predicts pharmacokinetics and clinical response to GDC-0084 in human recurrent high-grade glioma (Grand Canyon 8-13) - Oct 29, 2019 - Abstract #SNO2019SNO_856; P1 Using this composite multi-parametric MR-PET imaging response biomarker to predict PK, patients with an estimated Cmax >0.1 uM and AUC > 1.25 uM*hr demonstrated significantly longer PFS compared with patients with a lower estimated concentration and exposure (P=0.0039 and P=0.0296, respectively). Results from the current study suggest composite biomarkers created from multi-parametric MR-PET imaging targeting metabolic and/or physiologic processes specific to the drug mechanism of action may be useful for subsequent evaluation of treatment efficacy for larger phase II-III studies.
- |||||||||| Cantrixil (TRX-E-002-1) / Kazia
Biomarker, Preclinical, Journal: Mechanism of action of the third generation benzopyrans and evaluation of their broad anti-cancer activity in vitro and in vivo. (Pubmed Central) - Sep 28, 2019 In this study, we investigated the mechanism of action of the third-generation benzopyran compounds, TRX-E-002-1 and TRX-E-009-1...This finding along with immunostaining, in vitro polymerization assays, and animal experiments in both athymic and immunocompetent mice, demonstrates that these third-generation benzopyran compounds are potent tubulin polymerization inhibitors in vitro and in vivo, and this is the molecular basis of their anti-cancer activity in melanoma. These findings indicate these BP compounds may offer a novel anti-microtubule strategy for cancer intervention and provides the basis for further investigation into biomarkers of clinical sensitivity.
- |||||||||| GDC-0084 / Kazia
Journal: GDC-0084 inhibits cutaneous squamous cell carcinoma cell growth. (Pubmed Central) - Apr 3, 2019 In GDC-0084-treated tumor tissues PI3K-Akt-mTOR and DNA-PKcs activation were significantly inhibited. In summary, GDC-0084 inhibits human cSCC cell growth in vitro and in vivo through blocking PI3K-Akt-mTOR and DNA-PKcs signalings.
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