A5045665340- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- Microtubule and mitosis dynamics
- CAR-T cell therapy research
- Drug-Induced Hepatotoxicity and Protection
- Opioid Use Disorder Treatment
- Chronic Lymphocytic Leukemia Research
- Renal cell carcinoma treatment
- Blood properties and coagulation
- HER2/EGFR in Cancer Research
- Cancer Research and Treatments
- PI3K/AKT/mTOR signaling in cancer
- Erythrocyte Function and Pathophysiology
- Pain Management and Opioid Use
- Monoclonal and Polyclonal Antibodies Research
- Pancreatic function and diabetes
Novartis (United States)
2024-2025
Tris Pharma (United States)
2024
University of North Carolina at Chapel Hill
2023
American Pharmacists Association
2015
Mutations or silencing of the von Hippel Lindau (VHL) tumor suppressor gene accumulates hypoxia-inducible factors (HIFs). HIF-2α is implicated in oncogenesis ~50% patients with clear cell renal carcinoma (ccRCC) but, has been considered "undruggable". DFF332, an orally administered novel allosteric inhibitor showed dose-dependent antitumor efficacy preclinical models ccRCC. This first-in-human study evaluated safety, tolerability, activity, pharmacokinetics, and pharmacodynamics DFF332...
4513 Background: Targeting HIF2α inhibition has been proven to be an effective therapeutic option in patients (pts) with advanced clear cell renal carcinoma (ccRCC). DFF332, a small molecule inhibitor that selectively targets transcriptional activity, shown dose-dependent antitumor efficacy preclinical models of ccRCC. Methods: This is the first human, Phase I/Ib, open-label, multicenter, study (CDFF332A12101, NCT04895748) DFF332 adult pts The evaluated safety, tolerability, pharmacokinetics...
<p>Supplementary Figure S1. Time to all grade TRAE at different doses of DFF332. This swimmer plot illustrates the timeline AE onset for each patient in study. The x-axis represents time days, while y-axis lists individual patients. Different colors denote dose level which was allocated, and symbols indicate when adverse events started. AE, event; QD, once daily; QW, weekly; TRAE, treatment-related event.</p>
<p>Key inclusion and exclusion criteria</p>
<div>AbstractPurpose:<p>Mutations or silencing of the von Hippel–Lindau tumor suppressor gene accumulate hypoxia-inducible factors (HIF). HIF-2α is implicated in oncogenesis ∼50% patients with clear-cell renal cell carcinoma (ccRCC) but has been considered “undruggable.” DFF332, an orally administered novel allosteric inhibitor HIF-2α, showed dose-dependent antitumor efficacy preclinical models ccRCC.</p>Patients and Methods:<p>This first-in-human study evaluated...
<p>Supplementary Figure S2. Comparison of percentage changes in patients’ plasma levels erythropoietin between baseline and cycle 3 day 1 (A) with respect to their BOR (B) against the change hemoglobin levels. Statistical comparison was performed using a two-sample t-test; p < 0.05 considered significant. Boxplot (Figure A): central line box, median; interquartile range (IQR; 25th 75th percentile); whiskers, smallest largest values within 1.5 times IQR from lower upper quartiles;...
9509 Background: GNAQ/11 mutations occur in up to 95% of uveal melanomas (UM) and a subset non-uveal melanomas. Cell surface PMEL17 (gp100) is highly broadly expressed melanoma (including UM). SDZ475 (FR900359) potent inhibitor, however vivo toxicity has precluded clinical development. DYP688 an antibody drug conjugate that binds deliver the payload SDZ475. Methods: This first-in-human, open-label, multicenter, single-arm study (NCT05415072) patients (pts) with MUM other mutant aimed...
Antibody drug conjugates (ADC) are a promising class of oncology therapeutics consisting an antibody conjugated to payload via linker. DYP688 is novel ADC comprising signaling protein inhibitor (FR900359) that undergoes unique on-antibody inactivation in plasma, resulting complex pharmacology. To assess the impact FR on pharmacology and clinical developability, we performed translational modeling preclinical PK tumor growth inhibition (TGI) data, accompanied by mechanistic Krogh cylinder...