Phase I Study to Evaluate the Mass Balance, PK, Metabolism and Excretion of Berzosertib (Intravenous) Containing Microtracer [14C]Berzosertib in Participants With Advanced Solid Tumors (DDRiver Solid Tumors 208)

The study was conducted in two periods, Period 1 (mass balance) and Period 2 (extension). The purpose of Period 1 of this study was to provide a quantitative characterization of the mass balance, rates and routes of elimination, and metabolic pathways after a single intravenous administration of [14C]berzosertib. The purpose of Period 2 was to assess safety and efficacy of berzosertib in combination with topotecan.

Start Date15 Feb 2022

Sponsor / Collaborator

Merck Healthcare KGaA

NCT04807816

/ RecruitingPhase 2IIT

Targeting ATR in Soft-tissue Sarcomas: a Randomized Phase II Study. TARSARC Study

Multicenter, prospective, open-labeled, 2-arm, non-comparative randomized phase II trial to assess the antitumor activity of berzosertib in association with gemcitabine

Start Date09 Feb 2022

Sponsor / Collaborator

Institut Bergonié

[+1]

NCT04826341

/ RecruitingPhase 1/2IIT

A Phase I/II Study of Sacituzumab Govitecan Plus Berzosertib in Small Cell Lung Cancer, Extra-Pulmonary Small Cell Neuroendocrine Cancer and Homologous Recombination-Deficient Cancers Resistant to PARP Inhibitors

Background:
Small cell lung cancer and PARP inhibitor resistant tumors are aggressive cancers. Current treatments for people with these tumors yield little benefit. Researchers want to see if a combination of drugs can help.
Objective:
To find a safe combination of sacituzumab govitecan and berzosertib and to see if this will cause small cell lung cancer and PARP inhibitor resistant tumors to shrink.
Eligibility:
People ages 18 and older with a solid tumor, small cell lung cancer, or a homologous recombination-deficient cancer that is resistant to PARP inhibitors
Design:
Participants will be screened with:
Standard clinical exams and tests
EKG to test the heart
Medical documentation to confirm cancer diagnosis
Participants will get sacituzumab govitecan by vein on days 1 and 8 of each 21-day cycle. They will get berzosertib by vein on days 2 and 9. Treatment will continue as long as they can tolerate the drugs and their tumors are either stable or getting better.
Before treatment and at least once per cycle, participants will have a physical exam and blood tests. Before treatment and every 2 or 3 cycles, they will have a CT scan. They will have a contrast agent injected into a vein for the scan.
Participants will give blood and hair samples and tumor biopsies for research. Biopsies will be taken with a small needle under imaging guidance.
After they stop treatment, participants will have a visit 1 month later. They will then be contacted by phone or email every 3 months for the rest of their lives.

Start Date20 Sep 2021

Sponsor / Collaborator

National Cancer Institute

100 Clinical Results associated with Berzosertib

100 Translational Medicine associated with Berzosertib

100 Patents (Medical) associated with Berzosertib

205

Literatures (Medical) associated with Berzosertib

17 Mar 2025·ONCOGENE

PPP2R1A mutations cause ATR inhibitor sensitivity in ovarian clear cell carcinoma

Article

Author: Marlow, Rebecca ; Frankum, Jessica ; Alexander, John ; Sridhar, Sandhya ; Stewart, James ; Konde, Asha ; Song, Feifei ; Khalique, Saira ; Wicks, Andrew J ; Betteridge, Kai ; Krastev, Dragomir B ; Banerjee, Susana ; Lord, Christopher J ; Attygalle, Ayoma D ; Yang, William ; Tutt, Andrew N J ; Baxter, Joseph S ; Choudhary, Jyoti S ; Brough, Rachel ; Pettitt, Stephen J ; Natrajan, Rachael ; Vroobel, Katherine ; Zatreanu, Diana ; Roumeliotis, Theodoros I ; Yeung, Jason ; Haider, Syed ; Gulati, Aditi

Identification of ARID1A/ATR synthetic lethality led to ATR inhibitor phase II trials in ovarian clear cell carcinoma (OCCC), a cancer of unmet need. Using multiple CRISPR-Cas9 mutagenesis and interference screens, we show that inactivation of protein phosphatase 2A (PP2A) subunits, including PPP2R1A, enhance ATRi sensitivity in ARID1A mutant OCCC. Analysis of a new OCCC cohort indicates that 52% possess oncogenic PPP2R1A p.R183 mutations and of these, one half possessed both ARID1A as well as PPP2R1A mutations. Using CRISPR-prime editing to generate new isogenic models of PPP2R1A mutant OCCC, we found that PPP2R1A p.R183W and p.R183P mutations cause ATRi-induced S phase stress, premature mitotic entry, genomic instability and ATRi sensitivity in OCCC tumour cells. p.R183 mutation also enhanced both in vitro and in vivo ATRi sensitivity in preclinical models of ARID1A mutant OCCC. These results argue for the assessment of PPP2R1A mutations as a biomarker of ATRi sensitivity.

01 Mar 2025·Journal for ImmunoTherapy of Cancer

Oxaliplatin, ATR inhibitor and anti-PD-1 antibody combination therapy controls colon carcinoma growth, induces local and systemic changes in the immune compartment, and protects against tumor rechallenge in mice

Article

Author: Fauvre, Alexandra ; Milazzo, Louis-Antoine ; Lossaint, Gérald ; Sgarbura, Olivia ; Atis, Salima ; Marchive, Candice ; Vezzio-Vié, Nadia ; Gongora, Céline ; Andrade, Augusto Faria ; Michaud, Henri-Alexandre ; Garambois, Veronique ; Tosi, Diego ; Quenet, François ; Ursino, Chiara ; Combes, Eve ; Corbeau, Ileana ; Faget, Julien ; Khellaf, Lakhdar ; Culerier, Elodie ; Jeanson, Laura ; Bonnefoy, Nathalie ; Houede, Nadine

Background:

Colorectal cancer (CRC) is the third most common cancer type and one of the leading causes of cancer-related death worldwide. The treatment of advanced metastatic CRC relies on classical chemotherapy combinations (5-fluorouracil, oxaliplatin or irinotecan). However, their use is limited by the emergence of resistance mechanisms, including to oxaliplatin. In this context, we recently showed that the combination of oxaliplatin and ataxia telangiectasia and Rad3-related protein inhibition (VE-822) is synergistic and may have a potential therapeutic effect in metastatic CRC management.

Methods:

In this study, we investigated the role of the VE-822+oxaliplatin (Vox) combination on the immune response and its potential synergy with an anti-programmed-cell Death receptor-1 (PD-1) antibody. We used cell lines and organoids from metastatic CRC to investigate in vitro Vox efficacy and orthotopic syngeneic mouse models of metastatic CRC to assess the efficacy of Vox+anti-PD-1 antibody and identify the involved immune cells.

Results:

The Vox+anti-PD-1 antibody combination completely cured tumor-bearing mice and protected them from a rechallenge. Vox was associated with a reduction of tumor-infiltrated neutrophils, CD206+macrophages and regulatory T cells. Vox also induced a deep depletion of blood neutrophils. The increased bone marrow granulopoiesis failed to compensate for the Vox-mediated mature neutrophil depletion. Neutrophil depletion using a mouse recombinant anti-Ly6G antibody partially mimicked the Vox effect on the tumor microenvironment, but to a lower extent compared with the Vox+anti-PD-1 antibody combination. Vox, but not neutrophil depletion, led to the emergence of an Ly6C+PD-1+CD8+T-cell population in the blood and spleen of tumor-harboring mice. These cells were proliferating, and expressed IFN-γ, CD62L, CXCR3 and Eomes. Moreover, the proportion of tumor antigen-specific T cells and of CD122+BCL6+T cells, which shared phenotypic characteristics with stem-like CD8+T cells, was increased in treated mice.

Conclusions:

Our work strongly suggests that the Vox+anti-PD-1 antibody combination might significantly improve survival in patients with metastatic and treatment-refractory CRC by acting both on cancer cells and CD8+T cells.

10 Feb 2025·BRITISH JOURNAL OF CANCER

ATR inhibition potentiates FOLFIRINOX cytotoxic effect in models of pancreatic ductal adenocarcinoma by remodelling the tumour microenvironment

Article

Author: Chepeaux, Laure-Agnès ; Mathonnet, Muriel ; Colinge, Jacques ; Jean, Christine ; Tosi, Diégo ; Gongora, Céline ; Colombo, Pierre-Emmanuel ; Brager, Dorian ; Bousquet, Corinne ; Bruciamacchie, Marine ; Larbouret, Christel ; Evrard, Alexandre ; Garambois, Véronique ; Robin, Mathilde ; Belhabib, Ismahane ; Pourquier, Philippe ; Bonnefoy, Nathalie ; Bessede, Thomas ; Bigot, Kevin ; Michaud, Henri-Alexandre ; Vie, Nadia ; Jarlier, Marta ; Gros, Laurent

BACKGROUND:

In pancreatic ductal adenocarcinoma (PDAC), the dense stroma rich in cancer-associated fibroblasts (CAFs) and the immunosuppressive microenvironment confer resistance to treatments. To overcome such resistance, we tested the combination of FOLFIRINOX (DNA damage-inducing chemotherapy drugs) with VE-822 (an ataxia-telangiectasia and RAD3-related inhibitor that targets DNA damage repair).

METHODS:

PDAC spheroid models and organoids were used to assess the combination effects. Tumour growth and the immune and fibrotic microenvironment were evaluated by immunohistochemistry, single-cell analysis and spatial proteomics in patient-derived xenograft (PDX) and orthotopic immunocompetent KPC mouse models.

RESULTS:

The FOLFIRINOX and VE-822 combination had a strong synergistic effect in several PDAC cell lines, whatever their BRCA1, BRCA2 and ATM mutation status and resistance to standard chemotherapy agents. This was associated with high DNA damage and inhibition of DNA repair signalling pathways, leading to increased apoptosis. In immunocompetent and PDX mouse models of PDAC, the combination inhibited tumour growth more effectively than FOLFIRINOX alone. This was associated with tumour microenvironment remodelling, particularly decreased proportion of fibroblast activated protein-positive CAFs and increased anti-tumorigenic immune cell infiltration and interaction.

CONCLUSION:

The FOLFIRINOX and VE-822 combination is a promising strategy to improve FOLFIRINOX efficacy and overcome drug resistance in PDAC.

News (Medical) associated with Berzosertib

29 Apr 2025

·endpts.com

Artios drug exploits ‘replication stress’ in cancer, shrinking subset of tumors in early study

Artios Pharma, a startup developing drugs that weaken a tumor’s ability to maintain its DNA, announced positive results in a subset of patients with advanced cancer. It’s the first big data reveal for the Cambridge, UK-based startup, which has been relatively quiet since 2021, when it struck a drug discovery partnership with Novartis and raised $153 million in Series C financing. The company’s drug, called ART0380, inhibits a DNA repair enzyme called ATR. When administered with a low dose of the chemotherapy irinotecan, the drug shrank tumors in 37% of patients whose cancer was considered “deficient” in another DNA damage response protein dubbed ATM, according to data from a Phase 1/2 study. In patients whose tumors lacked the ATM protein entirely, the response rate was 50%, with a median duration of response of 5.7 months so far. The response rate was 22% in patients with low levels of ATM. Patients with the ATM protein, however, did not respond to the therapy. “All those patients unfortunately progress quickly and unfortunately die very quickly,” Artios Chief Medical Officer Ian Smith told Endpoints News in an interview. The new data, presented Tuesday at the American Association for Cancer Research meeting, comes from 58 patients with advanced-stage and metastatic solid tumors who were treated at the dose the company plans to use in a Phase 2 study. Artios CEO Niall Martin told Endpoints that the company has funds “through 2026.” He said the startup is looking to raise another round of private funding to test its ATR inhibitor in pancreatic and colorectal cancers before pursuing bigger and broader tissue-agnostic studies. Martin said the company’s partnership with Novartis, which wasn’t focused on its ATR inhibitor, identified several targets that could potentially be paired with Novartis’ radioligand therapies, including its prostate cancer drug Pluvicto, and discussions are underway on next steps. Artios had struck a partnership with Merck KGaA in 2020 to search for drugs that target other DNA repair proteins, but Martin told Endpoints that partnership has ended. Artios was founded in 2016 to discover a new wave of drugs that target complex networks of proteins dedicated to the faithful replication and preservation of our genomes. While cancer can survive, and even thrive, with some DNA repair enzymes missing, too many missing pieces can cause the cancer to self-destruct. A class of drugs called PARP inhibitors exploit this vulnerability by blocking the eponymous DNA repair protein in tumors that have mutations in genes called BRCA1 and BRCA2, which are also important for DNA repair. Several companies have been searching for the next combination of targets that can deliver a similar double whammy to tumors, but progress has been slow. “The field hasn’t really evolved much since PARP inhibitors,” Martin said. “So we’ve been really thinking about what are the layers of DNA damage that are created in tumors that could be used as their sort of Achilles heel.” One of those layers, according to Artios, is a phenomenon called replication stress, which can occur when DNA replication, a key step for dividing cells, is blocked. ATR and ATM are two proteins that detect and clear up these blockages. Many forms of chemotherapy obstruct DNA replication. By first inducing a bit more of that stress with a low dose of chemo — but not enough to kill the cancer itself — and then blocking ATR in tumors with little to no ATM, Artios hoped to deliver a triple whammy to tumors. “There’s always been a push to get rid of chemotherapy and have targeted drugs,” Smith said.“But if you can’t get rid of chemotherapy, what you can do is really minimize it. And that’s what we’ve done here.” Smith said the company saw two complete responses, including one in a 62-year-old female who had pancreatic cancer but has been off treatment and cancer-free since August 2023. Neutropenia, a decline in white blood cells, was the most common side effect seen in 53% of patients, with grade 3 neutropenia in 45% of patients. Anemia occurred in 41% of patients. Fatigue, diarrhea, nausea and vomiting were also common side effects. Several other drugmakers have developed their own ATR inhibitors, but lackluster results have caused some pharma companies, including Bayer and Roche, to discontinue or pare back these efforts. “ATR inhibitors have been languishing,” Smith said. “The response rates are low relative to the toxicity that you tend to get.” Roche cut its partnership with Repare Therapeutics in 2024, which paused its ATR inhibitor program earlier this year after modest responses in only 19% and 17% of endometrial and ovarian cancer patients, respectively. Merck KGaA dropped its first ATR inhibitor, berzosertib, but is still testing a second one, called tuvusertib. And AstraZeneca is testing its ATR inhibitor ceralasertib in a Phase 3 study in lung cancer with its immunotherapy Imfinzi, which is expected to complete in August. Artios executives told Endpoints that other ATR inhibitors have faltered for three reasons: the drug’s half-life was too long, leading to intolerable toxicity; the drug was tested as a monotherapy, leading to low efficacy; or the drug was paired with the wrong therapies or tested in the wrong genetic subtypes of cancer. Martin said the company plans to develop a companion diagnostic to identify patients that are most likely to respond to its drug, with an initial focus on ATM. But Artios is looking for other biomarkers that may make tumors vulnerable to ATM inhibitors too. “This whole process of replication stress can be in up to 30% to 40% of tumors,” Martin said. “So there’s a huge area of biology which no one really has tapped into.”

Clinical ResultPhase 3Phase 2

10 Apr 2024

·www.prnewswire.com

Blacksmith Medicines To Highlight Preclinical Oncology Data Demonstrating a Potent and Selective FEN1 Inhibitor Has Synergy with Multiple DDR Drug Classes at AACR Annual Meeting 2024

SAN DIEGO, April 10, 2024 /PRNewswire/ -- Blacksmith Medicines, Inc. (Blacksmith), a leading biopharma dedicated to discovering and developing medicines targeting metalloenzymes, today announced preclinical data on its oncology program targeting flap endonuclease 1 (FEN1), a structure-specific metallonuclease that cleaves 5' DNA flaps during replication and repair, at the American Association for Cancer Research (AACR) Annual Meeting 2024, taking place April 5-10 at the San Diego Convention Center, San Diego CA. "FEN1 has been identified as an important therapeutic metalloenzyme involved in DNA replication and repair but previous drug discovery efforts have been hampered by chemistry limitations resulting in inhibitors lacking potency and selectivity," said Zachary Zimmerman, Ph.D. CEO of Blacksmith. "Using our metalloenzyme fragment-based drug discovery approach, we have identified a highly potent and selective inhibitor of FEN1 having synergies with multiple DDR drug classes that include inhibitors of PARP, PARG, USP1, and ATR." The Blacksmith fragment-based drug discovery platform identified a novel metal-binding pharmacophore that binds to the two magnesium ions in the FEN1 active site. Further elaboration using fragment growth strategies resulted in highly potent and selective inhibitors. The current lead (BSM-1516) is ~65-fold more potent against FEN1 than its related enzyme Exonuclease 1 (Exo1) in biochemical assays (IC50 of 7 nM and 460 nM, respectively), an improvement of more than an order of magnitude in selectivity compared to earlier efforts. FEN1 target engagement in live cells was validated by cellular thermal shift assay (CETSA EC50 of 24 nM). Inhibition of FEN1 led to its increased association with chromatin in S-phase cells and recruitment of PARP1 enzyme. In clonogenic assay, BRCA2-deficient DLD1 cells were ~15-fold more sensitive to FEN1 inhibition than their isogenic BRCA2-wild-type counterparts (EC50 of 350 nM and 5 µM, respectively), confirming the increased susceptibility of HR deficient cancer cells to FEN1 inhibition. Treatment of BRCA2-deficient but not wild-type DLD1 cells with BSM-1516 resulted in cell cycle arrest accompanied by DNA damage signaling and accumulation of chromatin-bound RPA32, a marker of ssDNA. In FEN1-inhibitor-anchored CRISPR screen, it was observed that perturbations in EXO1, USP1, PARP1 and HR pathway genes sensitized cells to FEN1 inhibition. Synergistic relationships of BSM-1516 and its combination potential were further explored in viability studies with a panel of DDR inhibitors (n=25) in BRCA2-proficient and deficient cell lines. Strong synergy was identified with multiple drug classes that included inhibitors of USP1 (KSQ-4279), PARP (Olaparib, Niraparib, Talazoparib, AZD5305), PARG (PDD 00017273) and ATR (AZD6738, VE-822, Elimusertib). In vitro ADME assays and in vivo PK studies showed that BSM-1516 has properties suitable for in vivo testing, either as a single agent or in combination with synergistic DDR inhibitors, an investigation that is currently underway. Poster presentation details Abstract Number: 7148 Title: "Small molecule inhibitor of FEN1 nuclease utilizing a novel metal binding pharmacophore synergizes with inhibitors of USP1, PARP, PARG and ATR" Session Category: Experimental and Molecular Therapeutics Session Title: Novel Antitumor Agents 6 Session Date and Time: Wednesday April 10, 2024 9:00 AM - 12:30 PM Location: Poster Section 23 Poster Board Number: 10 About FEN1 Flap endonuclease 1 (FEN1) is a structure-specific di-magnesium metallonuclease that cleaves 5' DNA flaps during replication and repair. FEN1 is an attractive target for development of anticancer therapeutics because it is overexpressed in many tumor types and has a large number of synthetic lethality partners including genes in Homologous Recombination (HR) pathway. About metalloenzymes and the Blacksmith platform Metalloenzymes utilize a metal ion cofactor in the enzyme active site to perform essential biological functions. This diverse class of targets has historically been difficult to drug due to small molecule chemistry limitations that have plagued the industry. The Blacksmith metalloenzyme platform has solved this problem by leveraging the following: A large proprietary fragment library of metal-binding pharmacophores (MBPs); A comprehensive database containing a full characterization of the metalloenzyme genome including functions, metal cofactors, and associations to disease; A first-of-its-kind metallo-CRISPR library of custom single guide RNAs; An industry-leading metalloenzyme computational toolkit for docking, modeling and structure-based drug design; and A robust and blocking intellectual property estate covering bioinorganic, medicinal, and computational chemistry approaches for metalloenzyme-targeted medicines. About Blacksmith Medicines At Blacksmith Medicines, we are developing medicines targeting metal-dependent enzymes. Over 30% of known enzymes are metalloenzymes, covering all major enzyme classes: oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases. Metal ions, including magnesium, zinc, iron, manganese and copper, are the essential ingredient in these metalloenzymes. We recognized a large unmet need for new chemical matter and innovative approaches to drug this important class of enzymes. Our purpose-built platform for metalloenzyme-targeted medicines combines, for the first time in industry, a focused library of metal-binding pharmacophores with proprietary computational modeling approaches to rapidly and rationally design small molecule inhibitors that interact with key metal ions in the enzyme's active site. Our comprehensive knowledge of the metal environment and key active site interactions enables Blacksmith to rapidly build potent and selective inhibitors in a stepwise and predictable manner. Blacksmith has executed strategic drug discovery collaborations with Basilea Pharmaceutica International Ltd., Cyteir Therapeutics Inc., Eli Lilly and Company (Lilly), Hoffmann-La Roche Ltd., and Zoetis LLC., and has been awarded non-dilutive Federal funding agreements with CARB-X and NIH/NIAID. Blacksmith investors include Lilly, Evotec A.G., MP Healthcare Partners, MagnaSci Ventures, and Alexandria Venture Investments. For further information, please visit the company's website and LinkedIn Media Contact: Amy Conrad Juniper Point [email protected] 858-366-3243 SOURCE Blacksmith Medicines

AACR

09 Nov 2023

·www.prnewswire.com

China Leads in ATR Protein Inhibitors Clinical Trials, Accounting for Over 60% of Ongoing Research Efforts

DUBLIN, Nov. 9, 2023 /PRNewswire/ -- The "Global ATR Protein Inhibitors Clinical Trials & Market Opportunity Insight 2024" report has been added to ResearchAndMarkets.com's offering. A promising frontier in cancer pharmaceutical research, the inhibition of Ataxia telangiectasia and Rad3 related kinase (ATR kinase) is poised to revolutionize cancer treatment and extend its reach to neurodegenerative and infectious diseases. This exciting development is highlighted in the recently released "Global ATR Protein Inhibitors Clinical Trials & Market Opportunity Insight 2024" report, providing a comprehensive overview of this transformative field. Key Report Highlights: Clinical Trials: Over 15 ATR protein inhibitors are currently in clinical trials, demonstrating the significant investment and research efforts in this area. China Dominance: China leads ATR protein inhibitors clinical trials, accounting for over 60% of ongoing trials. Clinical Phase: ATR protein inhibitors are advancing rapidly, with several candidates reaching Phase III clinical trials. Pipeline Analysis: The report offers insights into the global ATR protein inhibitors clinical pipeline, categorized by company, indication, and phase. Development Trends: ATR inhibitors are expanding their scope to include neurodegenerative diseases and viral infections, opening new avenues for treatment. Competitive Landscape: The competitive landscape section provides insights into key players and their contributions to ATR inhibition research. ATR kinase, a serine/threonine-protein kinase, plays a pivotal role in maintaining genomic integrity and responding to DNA damage. Dysregulation of ATR has been linked to various diseases, particularly cancer. Inhibiting ATR presents a novel opportunity to exploit cancer cell vulnerabilities and enhance the effectiveness of existing therapies. The primary focus of ATR inhibition is in oncology, where ATR inhibitors have shown promise in augmenting the efficacy of DNA-damaging cancer treatments such as chemotherapy and radiation. These inhibitors hold great potential for combination therapies in various cancer types, including ovarian cancer, bile duct carcinoma, breast carcinoma, small cell cancer, high-grade neuroendocrine cancers, and hematological malignancies. Key candidates under investigation include ATG-018, Elimusertib (BAY 1895344), Camonsertib (RP-3500), and Ceralasertib (AZD6738), developed by Antengene, Bayer, Repare Therapeutics, and AstraZeneca, respectively. Recent research has expanded the scope of ATR inhibitors to neurodegenerative diseases, where ATR kinase's role in maintaining neuronal genomic activity presents a potential target for conditions like Parkinson's and Alzheimer's disease. Additionally, ATR inhibition has shown promise in combating microbial infections, particularly those caused by viruses like HIV-1 and COVID-19, opening avenues for novel therapeutics. The pharmaceutical industry has made significant investments in ATR inhibition, with numerous clinical trials underway to evaluate candidate efficacy. VE-821, developed by Vertex Pharmaceuticals, paved the way for the development of VE-822, now licensed to Merck as Berzosertib. These inhibitors, including M1774, have demonstrated promising results in early-phase clinical trials by enhancing cancer cell sensitivity to DNA-damaging chemotherapies, potentially reducing side effects. ATR inhibitors offer several advantages over traditional cancer therapies. They sensitize cancer cells to conventional treatments, potentially reducing dosages and side effects. ATR inhibition can also overcome resistance mechanisms that cancer cells develop against treatment, improving patient outcomes. Furthermore, ATR inhibitors enable a personalized approach to cancer treatment by targeting specific genetic vulnerabilities in patients. While challenges remain, such as refining patient selection criteria and understanding potential side effects, ATR inhibitors hold immense promise. As they continue to show potential, their integration into combination therapies is expected to reshape cancer treatment regimens. Advances in molecular profiling and genetic testing may further enable targeted ATR inhibition. The ongoing clinical and market trends for ATR inhibitors present a compelling narrative in the pharmaceutical domain. This innovative approach to targeting DNA damage response pathways has the potential to revolutionize cancer treatment and extend its reach to neurodegenerative and infectious diseases. With ongoing research revealing more about ATR kinase and its implications in different indications, the full potential of ATR inhibition is yet to be realized, promising a new wave of development in the global pharmaceutical market. Key Topics Covered: 1. Introduction to ATR Inhibition 1.1 Overview of ATR Protein & ATR Inhibition 1.2 History & Evolution of ATR Inhibitors 2. ATR Inhibitors: Research & Clinical Trials Overview by Indication 2.1 Solid Cancers 2.2 Hematological Cancers 3. Global ATR Inhibitors Market Outlook 3.1 Current Market Trends & Developments 3.2 Future Growth Avenues 4. ATR Inhibitors Development Trends by Region 4.1 US 4.2 EU 4.3 UK 4.4 Canada 4.5 China 4.6 Japan 4.7 Australia 5. Global ATR Protein Inhibitors Clinical Trials Overview 5.1 By Country 5.2 Indication 5.3 Phase 5.4 Therapy Class 6. Global ATR Protein Inhibitors Clinical Pipeline By Company, Indication & Phase 6.1 Research 6.2 Preclinical 6.3 Phase-I 6.4 Phase-I/II 6.5 Phase-II 6.6 Phase-III 7. Global ATR Inhibitors Market Drivers & Challenges 7.1 Drivers & Opportunities 7.2 Challenges & Restraints 8. Competitive Landscape 8.1 Antengene Corporation 8.2 Aprea 8.3 AstraZeneca 8.4 Bayer 8.5 Beijing Tide Pharmaceutical 8.6 Biocity Biopharmaceutics 8.7 Chipscreen Biosciences 8.8 IMPACT Therapeutics 8.9 Laevoroc Neuro-Oncology 8.10 Repare Therapeutics 8.11 Shanghai De Novo Pharmatech 8.12 Shanghai Junshi Biosciences 8.13 ShangPharma 8.14 Vertex Pharmaceuticals For more information about this report visit About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends. Media Contact: Research and Markets Laura Wood, Senior Manager [email protected] For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900 U.S. Fax: 646-607-1904 Fax (outside U.S.): +353-1-481-1716 Logo: SOURCE Research and Markets

Phase 3Phase 1

100 Deals associated with Berzosertib

External Link

KEGG	Wiki	ATC	Drug Bank
D11148	Berzosertib	-	DB11794

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Soft Tissue Sarcoma	Phase 2	France	Merck Healthcare KGaA	09 Feb 2022
Neoplasms	Phase 2	Germany	Merck KGaA	30 Jan 2022
Small Cell Lung Cancer	Phase 2	China	Merck Serono (Beijing) Pharmaceutical R&D Co., Ltd.	16 Sep 2021
Small Cell Lung Cancer	Phase 2	China	Merck Healthcare KGaA	16 Sep 2021
Small Cell Lung Cancer	Phase 2	China	BSP Pharmaceuticals SpA	16 Sep 2021
Islet Cell Carcinoma	Phase 2	United States	National Cancer Institute	01 Jun 2021
Advanced Lung Non-Small Cell Squamous Carcinoma	Phase 2	United States	National Cancer Institute	14 Apr 2021
Adenocarcinoma	Phase 2	United States	National Cancer Institute	16 Nov 2020
Gastrooesophageal junction cancer	Phase 2	United States	National Cancer Institute	16 Nov 2020
Metastatic gastric adenocarcinoma	Phase 2	United States	National Cancer Institute	16 Nov 2020

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03309150 (CTgov)	Phase 1	Advanced Malignant Solid Neoplasm	1	Berzosertib	bwttcnvxwo(totkncovqh) = uhcasutdls rjnyryajcl (umybnotvok, qtjxwjzgho - sfbhaujolo) View more	-	29 Nov 2024
NCT05246111 (CTgov)	Phase 1	Advanced Malignant Solid Neoplasm	6	[14C]Berzosertib ([14C]Berzosertib)	jvikayqpaw(waobtbcaeo) = zpbowaqvzx kcxucyvovn (qwmfpedjfv, 3.2) View more	-	22 Nov 2024
				Berzosertib+Topotecan (Berzosertib + Topotecan)	igdcznkmaz = cnplfvdufz jttjnoebcm (lyiqplolhf, nikhhsuxgk - hzrgioagth) View more
NCT04768296 (DDRiver SCLC 250, CTgov)	Phase 2	Recurrent Lung Small Cell Carcinoma	76	Berzosertib+Topotecan (Safety run-in Part (DL2) + Main Part: Berzosertib 210 mg/m^2 + Topotecan 1.25 mg/m^2)	doccnvighk = nrmzzlttkn upbknrrjdd (bgyoifaznd, blyoyzvttd - koqklasdxi) View more	-	26 Sep 2024
				Berzosertib+Topotecan (Safety run-in Part (DL 1): Berzosertib 105 mg/m^2 + Topotecan 1.25 mg/m^2)	nkbictxhyb = yivkuqamjk joxfvjgmwq (ktmzntqzst, ixetyvwtls - qjeylngmaj) View more
NCT03641547 (CHARIOT, Pubmed \| Br J Cancer) Manual	Phase 1	Esophageal Carcinoma \| Advanced Malignant Solid Neoplasm	34	Berzosertib with RT	ojnqopfzxh(fkfqitnwhz) = xefouhsdfy ccoygeugeu (psouvbpmng ) View more	Positive	24 Feb 2024
				Berzosertib cisplatinlcapecitabineecitabine	ojnqopfzxh(fkfqitnwhz) = yhylgagmam ccoygeugeu (psouvbpmng ) View more
NCT02567409 (ASCO_GU2024) Manual	Phase 2	Advanced Urothelial Carcinoma	87	gemcitabine + cisplatin + berzosertib	hmmvpjzdzz(aqmfbgeduy) = axlqpweezq ituitsnsap (rottqjuxit ) View more	Negative	25 Jan 2024
				gemcitabine + cisplatin	hmmvpjzdzz(aqmfbgeduy) = yxrrhngseq ituitsnsap (rottqjuxit ) View more
NCT03896503 (Pubmed \| JAMA Oncol)	Phase 2	Small Cell Lung Cancer	60	Topotecan alone	mfgjcnjnvj(mvnaptwcfa) = rdmffexzpi jgfrxgmmbf (fseokhnzmg, 1.2 - 5.1) View more	Positive	01 Dec 2023
				Topotecan + Berzosertib	mfgjcnjnvj(mvnaptwcfa) = eltyjumeox jgfrxgmmbf (fseokhnzmg, 2.8 - 4.6) View more
NCT02567409 (CTgov)	Phase 2	Renal Pelvis and Ureter Urothelial Carcinoma \| Urothelial Carcinoma of the Urinary Bladder \| Metastatic urothelial carcinoma	87	Berzosertib+Gemcitabine Hydrochloride+cisplatin (Arm A (Berzosertib, Gemcitabine Hydrochloride, Cisplatin))	plppcfipmf(ihepwcsrjx) = rftrejddfh dlfcufstek (uysslgxjpv, rluxrqfonf - nnmbgcmgqx) View more	-	17 Oct 2023
				Gemcitabine Hydrochloride+cisplatin (Arm B (Gemcitabine Hydrochloride, Cisplatin))	plppcfipmf(ihepwcsrjx) = ysolzocycn dlfcufstek (uysslgxjpv, cjxzwbgcpk - dvbimgvqps) View more
NCT03718091 (CTgov)	Phase 2	Solid tumor \| Advanced Malignant Solid Neoplasm \| Gastrointestinal Stromal Tumors ... View more	30	M6620 (Cohort T1: ATRX-mutant Leiomyosarcoma)	jstvenmhjz(qoovmdczub) = oueqvirshl uzngwfzfpb (vivnopjcph, hljhljridt - nbowdgpqcm) View more	-	07 Jul 2023
				M6620 (Cohort T2: Truncating ATM Mutation)	jstvenmhjz(qoovmdczub) = mskpohfzyg uzngwfzfpb (vivnopjcph, bpzjueyaei - bgbeyuiafj) View more
NCT03641313 (ASCO 12023 \| ASCO 22023) Manual	Phase 2	Gastrooesophageal junction cancer TP53 Mutation	17	Irinotecan Hydrochloride+Berzosertib	ewhmhdfgpk(vnicowtlqv) = pouhftvber stsvzmdsrd (zqihkotwwi ) View more	Negative	26 May 2023
NCT04826341 (AACR2023) Manual	Phase 1	Solid tumor ATM Mutation \| BRCA1 Mutation	-	sacituzumab govitecan+berzosertib	nknunfkuwn(gavgsdcfks) = painprbjzw wwheuzbirj (ybzowvsxla ) View more	Positive	14 Apr 2023

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