A5011312589- Colorectal and Anal Carcinomas
- Colorectal Cancer Treatments and Studies
- Gastrointestinal Tumor Research and Treatment
- Genetic factors in colorectal cancer
- Cancer therapeutics and mechanisms
- DNA Repair Mechanisms
- Cancer-related Molecular Pathways
- Head and Neck Cancer Studies
- HIV/AIDS drug development and treatment
- Colorectal Cancer Surgical Treatments
- Nonmelanoma Skin Cancer Studies
- Cancer Immunotherapy and Biomarkers
Saint Louis University
2024
Merck (Spain)
2020-2024
Merck (Germany)
2023
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...
•Genomic instability induced by the disruption of DNA damage response pathways can increase sensitivity to immunotherapies.•Peposertib, a DNA-dependent protein kinase inhibitor, had preclinical antitumor efficacy in combination with radiotherapy.•We assessed safety and activity peposertib + avelumab ± radiotherapy advanced solid tumors.•Peposertib was well tolerated at doses ≤200 mg b.i.d. ≤250 q.d. radiotherapy.•Peposertib limited clinical activity. IntroductionWe report results from phase...
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 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...
TPS4117 Background: Preoperative chemo-radiotherapy with or without sequential chemotherapy, followed by surgical intervention, is standard of care for patients locally advanced rectal cancer (LARC). However, 1/3 these still develop distant metastases, indicating the need more effective therapies. DNA-dependent protein kinase (DNA-PK) regulates a key DNA damage repair pathway double-strand break repair. Peposertib (M3814), potent, selective, orally administered DNA-PK inhibitor, has been...
<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-...