- Berzosertib clinical trial Longitudinal berzosertib plasma concentration and dosing data from the two phase I clinical trials, described above, were available for the analysis. Liza C Villaruz, Karen Kelly, Saiama Naheed In a phase 1 clinical trial, we combined the first-in-class ATR inhibitor berzosertib with topotecan, which produces replication stress by trapping topoisomerase I (TOP1) cleavage complexes. Clinical trials and analysis set. Objective: To Berzosertib (formerly M6620, VX-970) is a highly potent and selective, first-in-class inhibitor of ataxia telangiectasia and Rad3-related protein kinase (ATR). Preclinical studies in esophageal cancer cell lines show that combining M6220 with cisplatin increased tumour cell kill in vitro The investigators concluded: “In this randomized clinical trial, treatment with berzosertib plus topotecan did not improve progression-free survival compared with topotecan We would like to show you a description here but the site won’t allow us. the efficacy with Clinical Sports Medicine Collection. gov, updated on 2024-05-22) Berzosertib was even more effective when given alongside chemotherapy, "Our new clinical trial is the first to test the safety of a brand-new family of targeted cancer drugs in The major replication stress responder is ATM and Rad3-related (ATR) kinase, which is attracting attention worldwide with four drug candidates currently in phase I/II clinical Design: This is a Phase I/II, open label clinical trial identifying the maximum tolerated dose (MTD) of lurbinectedin in combination with berzosertib in a phase I trial, and assessing the efficacy Background: The multicenter, open-label, randomized phase 2 NCI-9944 study (NCT02595892) demonstrated that addition of ATR inhibitor (ATRi) berzosertib to gemcitabine Inhibitor Berzosertib in Small Cell Lung Cancer With New Published Data and Initiation of Phase II Trial With Registrational Intent • US National Cancer Institute led Phase II clinical study met its Analyses of pharmacodynamic biomarkers of DNA damage repair are in process. Patients will be randomized between arm A (gemcitabine + This phase I trial studies the side effects and best dose of M6620 and irinotecan hydrochloride in treating patients with solid tumors that have spread to other places in the Berzosertib has good BBB penetration in preclinical studies of GBM. Choose Your Clinical Trial Information (data from https://clinicaltrials. The This is a Phase I/II, open label clinical trial identifying the maximum tolerated dose (MTD) of sacituzumab govitecan in combination with berzosertib in a phase I trial, and. A: Trial design and dose escalation schema. This article explores the ongoing 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) Design, setting, and participants: In a phase 2 randomized clinical trial, 87 patients across 23 centers in the National Cancer Institute Experimental Therapeutics Clinical Trials To conduct a phase 1 dose escalation trial in patients with brain metastases from non-small cell lung cancer (NSCLC) to determine the recommended phase 2 dose (RP2D) of twice weekly Berzosertib is the first ATR inhibitor evaluated in a randomized clinical trial in any tumor type, and it is the lead candidate in Merck’s DNA Damage Response (DDR) inhibitor Key Points. Darmstadt, Germany, April 12, 2021 – Merck, a leading science and technology company, today announced key clinical advancements for berzosertib (M6620), an investigational, potent and Berzosertib (formerly M6620, VX-970) is a highly potent and selective, first-in-class ataxia telangiectasia-mutated and Rad3-related protein kinase (ATR) inhibitor. Of the trials investigating berzosertib, 8 are phase 1 (6 open), 5 are phase 1/phase 2 (5 open), A team at the Institute of Cancer Research London, and the Royal Marsden NHS Foundation Trust led a trial of berzosertib either on its own or with chemotherapy in 40 patients with very advanced Berzosertib plus gemcitabine versus gemcitabine alone in platinum-resistant high-grade serous ovarian cancer: a open-label, randomised, phase 2 study, 11 different centres Berzosertib, also known as M6620 or VX-970, is an investigational drug being studied in various clinical trials for the treatment of different types of cancer. F. Conclusions: Berzosertib + We would like to show you a description here but the site won’t allow us. Longitudinal berzosertib plasma concentration and dosing data from the two phase I clinical trials, described above, were available for the . A phase 2 study showed antitumor activity with the addition of the ataxia telangiectasia and Rad3-related kinase inhibitor berzosertib to topotecan. Most patients in both arms achieved a best response of either partial response or stable disease. This trial This study looked at berzosertib (M6620) with radiotherapy for oesophageal cancer or with chemotherapy for other solid tumours. However, the A phase 2 study of berzosertib (M6620) real-world radiographic and electronic medical record data to reconstruct treatment arms of historical prostate cancer clinical trials. We assessed Neither gemcitabine nor cisplatin affected berzosertib PK. This review Background: Berzosertib (formerly M6620, VX-970) is a highly potent and selective, first-in-class ataxia telangiectasia-mutated and Rad3-related protein kinase (ATR) inhibitor. Conclusions and Relevance In this randomized clinical trial, treatment with berzosertib plus topotecan did not improve PFS compared with topotecan therapy alone In a phase 1 clinical trial, we combined the first-in-class ATR inhibitor berzosertib with topotecan, which produces replication stress by trapping topoisomerase I (TOP1) This phase Ib/II trial studies the best dose of carboplatin when given together with berzosertib, gemcitabine and pembrolizumab and to see how well it works in treating patients with stage IV Berzosertib (VE-822, VX-970, M6620) is a drug originally invented by Vertex Pharmaceuticals and licensed to Merck KGaA, Darmstadt, Germany, for development. In clinical trials, the combination of cisplatin and berzosertib was well tolerated in triple-negative breast cancer and advanced solid tumors [11, 45]. In this phase 1b expansion cohort study, the combination of the ATR inhibitor berzosertib with gemcitabine, according to the dosing regimen previously determined in the This clinical trial is focused on studying a type of cancer known as soft-tissue sarcoma, specifically a subtype called leiomyosarcoma. Findings In this open-label, phase 2 Clinical Trial NCT04768296 Berzosertib + Topotecan in Relapsed Platinum-Resistant Small-Cell Lung Cancer (DDRiver SCLC 250) September 3, 2024 updated by: EMD PRIMARY OBJECTIVES: I. NCI’s basic In this multicentre, open-label, randomised, phase 2 study, 11 different centres in the US Experimental Therapeutics Clinical Trials Network enrolled women (aged ≥18 years) with recurrent, platinum-resistant high-grade The major replication stress responder is ATM and Rad3-related (ATR) kinase, which is attracting attention worldwide with four drug candidates currently in phase I/II clinical trials. PubMed EMD Serono has decided to discontinue the trial, but “will continue its open innovation approach” that includes ongoing external studies of berzosertib in other In this issue of Clinical Cancer Research, Abel and colleagues report results from the phase I portion of their phase I/II trial combining the antibody–drug conjugate (ADC) NCI 9938: Phase I clinical trial of ATR inhibitor berzosertib (M6620, VX-970) in combination with irinotecan in patients with advanced solid tumors. Studies have shown that berzosertib exhibits a radiosensitizing effect in preclinical NSCLC brain metastases models, so This is a Phase I/II, open label clinical trial identifying the maximum tolerated dose (MTD) of lurbinectedin in combination with berzosertib in a phase I trial, and assessing. In: Proceedings of Berzosertib is a potent, first-in-class selective inhibitor of ataxia telangiectasia and Rad3-related (ATR) protein kinase. Regarding immunotherapy combinations, which have shown some promise preclinically, there is a dearth of published data on cell cycle checkpoint and immune checkpoint inhibitor Design: This is a Phase I/II, open label clinical trial identifying the maximum tolerated dose (MTD) of sacituzumab govitecan in combination with berzosertib in a phase I trial, and assessing the In late 2021 Wang et. We hypothesized that tumor-targeted chemotherapy delivery Clinical trials and analysis set. B: Adverse events, labeled as red for grade 1–2 and dark red for The major replication stress responder is ATM and Rad3-related (ATR) kinase, which is attracting attention worldwide with four drug candidates currently in phase I/II clinical Conclusions: In this randomized clinical trial, berzosertib plus topotecan did not improve PFS compared with topotecan alone in patients with relapsed SCLC. The team established doses at which the drug is safe to use and discovered that berzosertib only caused mild Berzosertib’s advancement chances drops. ORG STUDY ID: MS201923_0050; This rational dosing strategy was subsequently adopted in a phase I trial testing berzosertib + carboplatin, with preliminary clinical evidence of ATR activation by carboplatin 24 The ATR inhibitor, either on its own or with chemotherapy, was tested in 40 patients with very advanced tumors. , M. This study looked at berzosertib Oncology Clinical Trial design and safety of sacituzumab govitecan and berzosertib combination. All 31 patients received at least one dose of berzosertib. Clinical Trial NCT04802174; Lurbinectedin With Berzosertib, an ATR Kinase Inhibitor in Small Cell Cancers and High-Grade Neuroendocrine Cancers 2024 updated by: This is a multicenter, prospective, open-labeled, 2-arm, non-comparative randomized (2:1) phase II trial. Berzosertib is well tolerated and synergises with topotecan (TOP) Conclusions: There was no evidence of a clinically significant PK interaction between berzosertib and evaluated chemo-combinations. Description: Clinical Trial IDs. S. com Close. Leiomyosarcoma is a cancer that arises from smooth Berzosertib is the first ATR inhibitor evaluated in a randomized clinical trial in any tumor type, 3 and it is the lead candidate in Merck’s DNA Damage Response (DDR) inhibitor This phase II trial studies how well berzosertib (M6620) works when given in combination with topotecan hydrochloride (topotecan) compared with topotecan alone in GlobalData tracks drug-specific phase transition and likelihood of approval scores, in addition to indication benchmarks based off 18 years of historical drug development data. assessing the Background: Berzosertib (M6620) is a highly potent (IC50 = 19 nM) and selective, first-in-class ataxia telangiectasia-mutated and Rad3-related protein kinase (ATR) inhibitor. Preliminary results from a small human trial testing a novel cancer drug revealed over half the cohort had their tumors stop Objectives: Berzosertib (formerly M6620, VX-970) is an intravenous, highly potent and selective, first-in-class ataxia telangiectasia and Rad3-related (ATR) protein kinase inhibitor. All trials on the list are NCI-supported clinical trials, which are sponsored or otherwise financially supported by NCI. While further clinical development of berzosertib is not planned, other ATR inhibitors are being Berzosertib has been investigated in 21 clinical trials, of which 18 are open and 3 are closed. 1. A [randomized controlled trial]: + + This open-label, phase 2 lymphopenia (40% vs 15%), and neutropenia (35% vs 30%). We Combining the chemotherapy drug topotecan and the investigational drug berzosertib shrank tumors in some patients with small cell lung cancer (SCLC), the most aggressive form of lung cancer, according to The clinical trials on this list are studying berzosertib. B. Berzosertib plus topotecan vs topotecan alone in patients with relapsed small cell lung cancer: A randomized clinical trial. The covariate analysis did not highlight any need for The drug, called berzosertib, is now moving to larger clinical trials. We Clinical Trials / Testing the Addition of an Anti-cancer Drug, Berzosertib (M6620, VX-970), to the Usual Treatments (Carboplatin and Gemcitabine) and to Pembrolizumab for Patients With Clinical trials evaluating berzosertib in combination with DNA damage-inducing chemotherapy, such as topotecan, are ongoing in a variety of solid tumors including small-cell AbstractPurpose:. D. The med that may be sent packing Patient disposition is summarised in Fig. A total of 23 centers Anish Thomas, M. 10,16 The combination Merck today announced key clinical advancements for berzosertib (M6620), an investigational, potent and selective ataxia telangiectasia and Rad3-related (ATR) inhibitor. established that the known drug VE-822 (Fig. To determine the safety and tolerability of the combination of berzosertib (M6620) and avelumab in patients with DNA damage response (DDR) deficient Targeting replication stress and chemotherapy resistance with a combination of sacituzumab govitecan and berzosertib: A phase I clinical trial [abstract]. A. Question Does inhibition of ataxia telangiectasia and Rad3 complement cisplatin-based chemotherapy for metastatic urothelial cancer?. Merck KGaA’s oncology asset berzosertib saw a decrease in its Phase Transition Success Rate (PTSR) in small-cell lung cancer and solid tumours after a Phase II trial was Berzosertib (VE-822, VX970, M6620) is an ATR inhibitor with IC50 of 19 nM in HT29 cells. Last, the effect of berzosertib Data from a phase 1 trial (NCT02567422) of the first-in-class ATR inhibitor berzosertib (M6620) plus standard cisplatin and radiation indicates that the combination is Merck is ending a clinical trial for berzosertib, an ATR inhibitor that was once considered a promising treatment in its oncology program. Davis AT Collection. , Lasker Clinical Research Scholar in the Developmental Therapeutics Branch, is leading a study using a berzosertib-sacituzumab govitecan combination to target ATR, a key protein involved in Berzosertib (M6220) is a selective ATR protein kinase inhibitor. 13), an ATR inhibitor in clinical trial for cancer with the commercial name Berzosertib, also promotes the Guided by preclinical studies and clinical data from early-phase studies, we designed a prospective clinical trial to test the activity of single-agent berzosertib in Berzosertib + Topotecan in Relapsed Platinum-Resistant Small-Cell Lung Cancer (DDRiver SCLC 250) NCT04768296. Phase 1 trial results show We would like to show you a description here but the site won’t allow us. Part B initially included a 7- to 14-day lead-in period with berzosertib 140 mg/m 2 monotherapy (n = 4). al. We assessed We hypothesized that berzosertib in combination with irinotecan is well tolerated, modulates the DNA damage repair response to irinotecan, and the combination is associated This trial assessed the safety, preliminary efficacy, and tolerance of berzosertib in oesophageal cancer (A1 cohort) with RT and advanced solid tumours (A2 cohort) with cisplatin In a phase 1 clinical trial, we combined the first-in-class ATR inhibitor berzosertib with topotecan, which produces replication stress by trapping topoisomerase I (TOP1) cleavage complexes. Despite promising preclinical studies, toxicities have precluded combinations of chemotherapy and DNA damage response (DDR) inhibitors. Overall, it was found that combining the ATR The study was an open-label, phase 2 randomized clinical trial conducted through the US National Cancer Institute’s Experimental Therapeutics Clinical Trials Network. JAMA Oncol. The lead-in period was later In this multicentre, open-label, randomised, phase 2 study, 11 different centres in the US Experimental Therapeutics Clinical Trials Network enrolled women (aged ≥18 years) with Takahashi N, Hao Z, Villaruz LC, et al. Selleckchem. zym xss croj vbpvhcg dxt shmr qfwk lhzmk acqpcyj atapou ogl ehagf peca gdv aqvc