"The idea is that if there are cancer cells with problems in both DNA replication and mitosis, an ATR inhibitor may be the best drug to target it," said Dr. Zou. Despite olaparib and ATR inhibitors demonstrating various degrees of monotherapy efficacy in ATM-deficient cancers [13,14,15, 27,28,29, 60, 61], our work highlights the importance of exploring . ATR, in particular, is important in the response to DNA replication stress, or replicative stress, which is caused by different insults including oncogene activation, chemotherapy, and radiation therapy.
Combination ATR and PARP Inhibitor (CAPRI) Trial With AZD6738 and Olaparib in Recurrent Ovarian Cancer (CAPRI) [ClinicalTrials.gov Identifier: NCT03462342] 2.
Considering the promising preclinical data for these agents, there remains considerable optimism for successful clinical outcomes in these trials. The Company's pipeline includes its lead product candidate, RP-3500, a potential leading ATR inhibitor currently in Phase 1/2 clinical development, its second clinical candidate, RP-6306, a . Known hypersensitivity to any of the ingredients of RP-3500. Where Trials Take Place. Clinical Trial Details. ATR inhibitors, ATR protein, Biopharma, Cancer, Coronavirus Disease 2019 (COVID-19), DNA, DNA Repair, Kinase Inhibitors, Los Angeles (UCLA), R&D, SARS-CoV-1, Small Molecules Merck KGaA's ATR Inhibitor Shows Promise in Both Cancer and COVID-19 ATR Inhibitor BAY 1895344 Plus Niraparib Phase 1b Study in Advanced Solid Tumors and Ovarian Cancer. We also discuss the potential mechanisms by which ATR and CHK1 inhibition . Here, we review the status of the development of ATR and CHK1 inhibitors. Particularly, the antimetastatic effect of combined Wee1/ATR inhibition and the low toxicity of ATR inhibitors . ATARI is a multi-centre, open-label, multiple two-stage parallel cohorts phase II clinical trial for patients with relapsed gynaecological cancers, with ARID1A-deficient ('loss') and "no loss." The trial tests the ATR inhibitor drug AZD6738 and a PARP inhibitor drug olaparib to assess the response in groups of patients selected based on their . ATR is a protein that keeps the cell cycle in check when the DNA is damaged. This is a clinical trial for men and women of 18 years of older who were diagnosed with: - Castration-resistant prostate cancer (CRPC) - HER2-negative breast cancer that is hormone-receptor positive .
Efforts are underway to identify the best clinical setting for these inhibitors, including type of tumor, its genetic background, and biomarkers present in the tumor [ [ 5 ] ]. The ATR(ataxia-telangiectasia and Rad3 related protein) inhibitor BAY1895344 is developed for the treatment of patients with advanced solid tumors and lymphomas. In a first-in-human, Phase I trial, researchers at The University of Texas MD Anderson Cancer Center discovered that ATR inhibitor RP-3500 was safe and well tolerated with promising clinical benefit. The clinical trial of the ATR (Ataxia telangiectasia and Rad3-related kinase) inhibitor is an open-label, multi-center, Phase I/IIa study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ART0380 as a monotherapy and in combination with gemcitabine in patients with advanced or metastatic solid cancers. Methods: Single agent sensitivity to VE-821 (ATR inhibitor) and olaparib (PARP inhibitor), and the combination, was determined using cell proliferation and clonogenic assays, in HR-NB cell lines. The solubility, bioavailability and pharmacokinetic properties of AZD6738 are better than those of AZ20. Veliparib and ATR kinase inhibitor M6620 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The ATARI clinical trial (ATr inhibitor in combination with olaparib in gynecological cancers with ARId1A loss or no loss, NCT04065269) is the first clinical trial which aims to test the hypothesis that ARID1A defective ovarian and endometrial clear cell carcinomas are more sensitive to ATR inhibition.
This will be the first in human study for the ATR inhibitor of IMPACT Therapeutics, representing a major leap of the company's global development . AZD6738, an analog of AZ20, is the second ATR inhibitor in clinical trials. Artios raises $153M to fund DNA damage repair clinical trials. BAY 1895344: First-In-Human Study of ATR Inhibitor BAY 1895344 in Patients with Advanced Solid Tumors and Lymphomas . Kim H, George E, Ragland RL, et al. A Multicenter, Non-randomized, Open-label Phase 1b Study to Determine the Maximum Tolerated and Recommended Phase 2 Dose of the ATR Inhibitor Elimusertib in Combination With Pembrolizumab and to Characterize Its Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumor Activity in Participants With Advanced Solid Tumors
Notably, ATR inhibitors were found to exhibit strong synergism with PARP-inhibitors in sensitizing cancers17,40-43, although the mechanism behind such synergy remains elusive. Berzosertib is the first ATR inhibitor evaluated in a randomized clinical trial in any tumor type, 3 and it is the lead candidate in EMD Serono's DNA Damage Response (DDR) inhibitor . 36). Berzosertib is an investigational, potent and selective inhibitor of the ataxia telangiectasia and Rad3-related (ATR) protein that blocks ATR activity in cells. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and . It ensures the cells only divide when the DNA is repaired correctly. AZ20 is another selective and potent inhibitor of ATR that inhibited the proliferation of LoVo colorectal adenocarcinoma cells in vitro as a single agent . Inhibition of ATR with an ATR inhibitor either as a monotherapy or in combination with DNA- damaging chemotherapy drugs, ionizing radiation, immune checkpoint blockers, or PARP inhibitors is being tested in early-phase clinical trials in advanced solid tumors and hematological malignancies. Phases of Clinical Trials . Satya Das, MD "Unfortunately, PARP inhibitors have a pretty limited activity for patients with the types of cancers in this clinical trial," Das said. Serine/threonine-protein kinase ATR also known as ataxia telangiectasia and Rad3-related protein (ATR) or FRAP-related protein 1 (FRP1) is an enzyme that, in humans, is encoded by the ATR gene. In this study, researchers confirmed when PARP inhibitors are combined with ATR inhibitors, the cell death of IDH -1/2 cancer cells is enhanced compared to a PARP inhibitor alone. Berzosertib is an investigational, potent and selective inhibitor of the ataxia telangiectasia and Rad3-related (ATR) protein that blocks ATR activity in cells. Importantly, the recently reported phase I clinical trial of BAY 1895344 in adult solid tumours also employed a 3 day on/4 day off treatment regimen that was tolerated, supporting use in the clinic 35. The ATARI clinical trial is an international, academic sponsored phase II clinical trial in which patients with ovarian and endometrial clear cell carcinoma, along with other rare gynecological tumors, are treated with the ATR inhibitor, ceralasertib (AstraZeneca), with or without the PARP inhibitor, olaparib (Lynparza, AstraZeneca) . PATIENTS AND METHODS This phase I trial assessed the ATR inhibitor M6620 (VX-970) as monotherapy (once or twice weekly) and combined with . SHANGHAI, Oct. 29, 2021 /PRNewswire/ -- IMPACT Therapeutics announced that its ATR inhibitor IMP9064 has received the IND clearance from the U.S. Food and Drug Administration (FDA) for the Phase I/II clinical study, which will begin soon in the U.S. SHANGHAI, Oct. 29, 2021 /PRNewswire/ -- IMPACT Therapeutics announced that its ATR inhibitor IMP9064 has received the IND clearance from the U.S. Food and Drug Administration (FDA) for the Phase I/II clinical study, which will begin soon in the U.S. Figure 1. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA.
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