A5089701962- Estrogen and related hormone effects
- Neuroblastoma Research and Treatments
- Prostate Cancer Treatment and Research
- Cancer, Lipids, and Metabolism
- Cancer Treatment and Pharmacology
- Inflammatory mediators and NSAID effects
- Cancer therapeutics and mechanisms
- Hormonal and reproductive studies
- Radiopharmaceutical Chemistry and Applications
- Cell death mechanisms and regulation
Sunesis (United States)
2024
Abstract Purpose: Increased glucocorticoid receptor (GR) signaling is a proposed compensatory mechanism of resistance to androgen (AR) inhibition in metastatic castration-resistant prostate cancer (mCRPC). ORIC-101 potent and selective orally-bioavailable GR antagonist. Patients Methods: Safety, pharmacokinetic/pharmacodynamic, antitumor activity combination with enzalutamide were studied patients mCRPC progressing on enzalutamide. doses ranging from 80 240 mg once daily tested 160 daily....
<div>AbstractPurpose:<p>Increased glucocorticoid receptor (GR) signaling is a proposed compensatory mechanism of resistance to androgen (AR) inhibition in metastatic castration-resistant prostate cancer (mCRPC). ORIC-101 potent and selective orally-bioavailable GR antagonist.</p>Patients Methods:<p>Safety, pharmacokinetic/pharmacodynamic, antitumor activity combination with enzalutamide were studied patients mCRPC progressing on enzalutamide. doses ranging from 80 240...
<p>Supplementary Figure 1. Nonclinical Mechanisms of Potential Ineffective Dual AR/GR Inhibition</p>
<div>AbstractPurpose:<p>Increased glucocorticoid receptor (GR) signaling is a proposed compensatory mechanism of resistance to androgen (AR) inhibition in metastatic castration-resistant prostate cancer (mCRPC). ORIC-101 potent and selective orally-bioavailable GR antagonist.</p>Patients Methods:<p>Safety, pharmacokinetic/pharmacodynamic, antitumor activity combination with enzalutamide were studied patients mCRPC progressing on enzalutamide. doses ranging from 80 240...
<p>Supplementary Figure 1. Nonclinical Mechanisms of Potential Ineffective Dual AR/GR Inhibition</p>
Abstract Purpose: In preclinical models, glucocorticoid receptor (GR) signaling drives resistance to taxane chemotherapy in multiple solid tumors via upregulation of antiapoptotic pathways. ORIC-101 is a potent and selective GR antagonist that was investigated combination with as an anticancer regimen preclinically phase 1 clinical trial. Patients Methods: The ability reverse assessed cell lines xenograft study (NCT03928314) conducted patients advanced determine the dose, safety, antitumor...
<p>GR antagonism by ORIC-101 overcomes taxane resistance in preclinical models. <b>A</b> and <b>B,</b> Effect of on dexamethasone-induced chemoprotection <i>in vitro</i> as measured (<b>A</b>) caspase 3/7 apoptosis assays (<b>B</b>) colony formation assays, three TNBC lines (HCC1806, MDA-MB-231, Hs578T), PDAC (BxPC3, SW1990, PSN1), ovarian cancer line COV362. Veh: vehicle; Dex: 30 nmol/L dexamethasone; 101: 0.5 μmol/L...
<p>TRAEs occurring in at least 10% of dose expansion patients or grade 3 severity treated the RP2D</p>
<p>TRAEs occurring in at least 10% of dose expansion patients or grade 3 severity treated the RP2D</p>
<p>Study disposition flow diagram of patient disposition. Note: int, intermittent regimen ORIC-101 administered 5 days on, 2 off for 21 out 28-day cycles; cont, continuous AE, adverse event; clin, clinical; OST, other solid tumors; PD, progressive disease; radiog, radiographic.</p>
<p>Study disposition flow diagram of patient disposition. Note: int, intermittent regimen ORIC-101 administered 5 days on, 2 off for 21 out 28-day cycles; cont, continuous AE, adverse event; clin, clinical; OST, other solid tumors; PD, progressive disease; radiog, radiographic.</p>
<p>ORIC-101 pharmacodynamics in PBMCs and tumor specimens. <b>A,</b> Pharmacodynamic (PD) modulation (average expression of GR target genes <i>FKBP5</i>, <i>GILZ</i>, <i>PER1</i>) on day 1 cycle as observed 40 dose expansion patients with PBMC sample collection cortisol assessment at C1D1 (pre-dose 6 hours post-dose), pre-dose levels >200 nmol/L. Samples are colored by cohort. <b>B,</b> PD suppression from (pre-dose) to 15...
<p>ORIC-101 pharmacodynamics in PBMCs and tumor specimens. <b>A,</b> Pharmacodynamic (PD) modulation (average expression of GR target genes <i>FKBP5</i>, <i>GILZ</i>, <i>PER1</i>) on day 1 cycle as observed 40 dose expansion patients with PBMC sample collection cortisol assessment at C1D1 (pre-dose 6 hours post-dose), pre-dose levels >200 nmol/L. Samples are colored by cohort. <b>B,</b> PD suppression from (pre-dose) to 15...
<p>Antitumor activity at the RP2D</p>