A5024908584- Colorectal and Anal Carcinomas
- Colorectal Cancer Treatments and Studies
- Gastrointestinal Tumor Research and Treatment
- Genetic factors in colorectal cancer
- TGF-β signaling in diseases
- DNA Repair Mechanisms
- Metal-Catalyzed Oxygenation Mechanisms
- Medical Imaging Techniques and Applications
- Lung Cancer Treatments and Mutations
- Head and Neck Cancer Studies
- Cancer Immunotherapy and Biomarkers
- Cancer-related Molecular Pathways
- HIV/AIDS drug development and treatment
- Cancer therapeutics and mechanisms
- Colorectal Cancer Surgical Treatments
- Nonmelanoma Skin Cancer Studies
Ono Pharmaceutical (United States)
2021-2024
Research & Development Institute
2021
DNA-dependent protein kinase (DNA-PK) plays a key role in the repair of DNA double strand breaks via nonhomologous end joining. Inhibition DNA-PK can enhance effect break inducing anticancer therapies. Peposertib (formerly "M3814") is an orally administered, potent, and selective small molecule inhibitor that has demonstrated radiosensitizing antitumor activity xenograft models was well-tolerated monotherapy. This phase 1 trial (National Clinical Trial 02516813) investigated maximum...
Abstract Purpose: Peposertib—an orally administered DNA-dependent protein kinase inhibitor—has shown potent radiosensitization in preclinical models. This dose-escalation study (NCT03770689) aimed to define the maximum tolerated dose (MTD) and recommended phase II (RP2D) of peposertib plus capecitabine-based chemoradiotherapy (CRT) assessed its safety efficacy locally advanced rectal cancer. Patients Methods: were treated for 5 5.5 weeks with 50- 250-mg once daily, capecitabine 825 mg/m2...
Abstract M4076 is a potent and selective oral inhibitor of ataxia-telangiectasia mutated (ATM), key kinase the DNA damage response (DDR) involved in double-strand break repair. Preclinically, when combined with damage-inducing therapy or other DDR inhibitors caused unrestricted cell cycle progression accumulation, resulting tumor death. Part 1A this ongoing open-label study (NCT04882917) evaluated safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), maximum tolerated dose...
Abstract Peposertib is an orally administered inhibitor of DNA‐dependent protein kinase. We evaluated the effect food on its pharmacokinetics, and examined pharmacokinetics oral suspension (OS) disintegrated tablets, in a phase I, open‐label, crossover three‐period study (NCT04702698). Twelve healthy volunteers were randomized to one six treatment sequences. They received single dose peposertib 100 mg as film‐coated tablets under fasted or fed conditions (“tablet fasted” “tablet fed”) OS...
<div>AbstractPurpose:<p>Peposertib—an orally administered DNA-dependent protein kinase inhibitor—has shown potent radiosensitization in preclinical models. This dose-escalation study (NCT03770689) aimed to define the maximum tolerated dose (MTD) and recommended phase II (RP2D) of peposertib plus capecitabine-based chemoradiotherapy (CRT) assessed its safety efficacy locally advanced rectal cancer.</p>Patients Methods:<p>Patients were treated for 5 5.5 weeks with 50-...
<p>Kaplan-Meier curve of disease-free survival</p>
<p>Mean peposertib plasma concentration-time profiles after single- and multiple-dose administration</p>
<p>Study design</p>
<p>Supplementary methods and results with references</p>
<p>. pDNA-PK/tDNA-PK ratios in PBMCs stimulated with bleomycin, pre- and post-dosing peposertib.</p>
<p>Mean peposertib plasma concentration-time profiles after single- and multiple-dose administration</p>
<p>Study design</p>
<p>Kaplan-Meier curve of disease-free survival</p>
<div>AbstractPurpose:<p>Peposertib—an orally administered DNA-dependent protein kinase inhibitor—has shown potent radiosensitization in preclinical models. This dose-escalation study (NCT03770689) aimed to define the maximum tolerated dose (MTD) and recommended phase II (RP2D) of peposertib plus capecitabine-based chemoradiotherapy (CRT) assessed its safety efficacy locally advanced rectal cancer.</p>Patients Methods:<p>Patients were treated for 5 5.5 weeks with 50-...