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

204

Literatures (Medical) associated with Berzosertib

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 ; Vezzio-Vié, Nadia ; Gongora, Céline ; Marchive, Candice ; Andrade, Augusto Faria ; Michaud, Henri-Alexandre ; Garambois, Veronique ; Tosi, Diego ; Quenet, François ; Ursino, Chiara ; Combes, Eve ; Faget, Julien ; Corbeau, Ileana ; 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 ; Colinge, Jacques ; Mathonnet, Muriel ; 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.

01 Feb 2025·RADIOTHERAPY AND ONCOLOGY

Interferon signaling is enhanced by ATR inhibition in glioblastoma cells irradiated with X-rays, protons or carbon ions

Article

Author: Syljuåsen, Randi G ; Edin, Nina Frederike Jeppesen ; Savu, Diana I ; Malinen, Eirik ; Temelie, Mihaela ; Lindbergsengen, Lilian ; Chevalier, François ; Serban, Ana Maria ; Eek Mariampillai, Adrian ; Rødland, Gro Elise ; Gilbert, Antoine

BACKGROUND AND PURPOSE:

Interferon (IFN) signaling plays an important role in antitumor immune responses. Inhibitors of the DNA damage response, such as ATR inhibitors, can increase IFN signaling upon conventional radiotherapy with X-rays. However, it is not known whether such inhibitors also enhance IFN signaling after irradiation with high linear energy transfer (LET) particles.

MATERIALS AND METHODS:

Human glioblastoma U-251 and T98G cells were irradiated with X-rays, protons (LET: 4.8 and 41.9 keV/µm) and carbon ions (LET: 28 and 73 keV/µm), with and without ATR inhibitor (VE-822) or ATM inhibitor (AZD1390). DNA damage signaling and cell cycle distribution were analyzed by immunoblotting and flow cytometry, and radiosensitivity was assessed by clonogenic survival assay. IFN-β secretion was measured by ELISA, and STAT1 activation was examined by immunoblotting.

RESULTS:

High-LET protons and carbon ions caused stronger activation of the DNA damage response compared to low-LET protons and X-rays at similar radiation doses. G2 checkpoint arrest was abrogated by the ATR inhibitor and prolonged by the ATM inhibitor after all radiation types. The inhibitors increased radiosensitivity, as measured after X- and carbon ion irradiation. ATR inhibition increased IFN signaling following both low-LET and high-LET irradiation. ATM inhibition also increased IFN signaling, but to a lesser extent. Notably, both cell lines secreted significantly more IFN-β when the inhibitors were combined with high-LET compared to low-LET irradiation.

CONCLUSION:

These findings indicate that DNA damage response inhibitors can enhance IFN signaling following X-, proton and carbon ion irradiation, with a strong positive dependency on LET.

News (Medical) associated with Berzosertib

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

11 Sep 2023

·synapse.patsnap.com

Important Target in Synthetic Lethality: ATR Inhibitors

The Ataxia telangiectasia and Rad-3 related protein kinase (ATR) is a member of the PIKK protein kinase family, and it is involved in numerous complex DNA damage repair mechanisms. Consequently, these mechanisms help to maintain genome integrity when the body deals with various genomic insults. Once DNA is damaged, a post-translational modification network can be activated to initiate damage checkpoints, subsequently inducing DNA repair and cellular apoptosis, a process known as the DNA damage response (DDR). ATR has the ability to activate cellular responses following DNA damage and can halt cell cycle progression, stabilize replication forks, and repair DNA. This process not only circumvents cell apoptosis but also plays an essential role in life activities. As a type of DNA damage response mechanism, the ATR pathway plays a crucial inhibitory role in tumor survival. Inducing ATR pathway-dependent malignant tumor cell death serves as an ideal target for developing low-toxicity, high-efficacy targeted anti-tumor drugs. Synthetic lethality refers to a scenario where a mutation in either of two non-lethal genes does not affect cell survival, but simultaneous mutations in both genes can specifically trigger cell death. Research has found that ATM and ATR kinases are activated or upregulated in cancer cells, and ATR serves as a synthetic lethal target for ATM mutations. Tumor cells deficient in ATM are more susceptible to ATR inhibitors. The selective inhibition between the two offers a new approach to tumor treatment and provides a new tool for tumor research. ATR Competitive LandscapeAccording to the data provided by Patsnap Synapse-Global Drug Intelligence Database: the following figure shows that as of 8 Sep 2023, there are a total of 24 ATR drugs worldwide, from 36 organizations, covering 45 indications, and conducting 127 clinical trials. 👇Please click on the picture link below for free registration or login directly if you have freemium accounts, you can browse the latest research progress on drugs , indications, organizations, clinical trials, clinical results, and drug patents related to this target. The current competitive landscape of target ATR in the pharmaceutical industry is dominated by companies like AstraZeneca PLC, Merck KGaA, and National Cancer Institute. These companies have a significant number of drugs in various development phases, indicating their commitment to research and development in this area. The approved indications for drugs under the target ATR cover a wide range of cancers, highlighting the potential impact of these drugs in treating different types of cancer. The rapid progress of small molecule drugs suggests intense competition in the development of innovative drugs. However, the presence of biosimilars is not mentioned in the provided data. The United States, China, and the European Union are the leading countries/locations in terms of development under the target ATR, with China showing notable progress. Overall, the target ATR presents a promising opportunity for the pharmaceutical industry, with a focus on cancer treatment and the development of small molecule drugs. Phase III Clinical Trial of ATR Inhibitor: CeralasertibCeralasertib is a small molecule drug that targets the protein ATR. It is being developed by AstraZeneca Pharmaceutical Co., Ltd. and is currently in Phase 3 clinical trials, both globally and in China. The drug has shown potential in treating a wide range of therapeutic areas, including neoplasms, hemic and lymphatic diseases, immune system diseases, digestive system disorders, endocrinology and metabolic diseases, skin and musculoskeletal diseases, respiratory diseases, and urogenital diseases. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. In terms of active indications, Ceralasertib has demonstrated efficacy in metastatic non-small cell lung cancer, solid tumors, osteosarcoma, pancreatic cancer, cholangiocarcinoma, prostatic cancer, small cell lung cancer, melanoma, breast cancer, triple negative breast cancer, B-cell chronic lymphocytic leukemia, non-small cell lung cancer, ovarian cancer, squamous cell carcinoma, stomach cancer, chronic myelogenous leukemia, diffuse large B-cell lymphoma, myelodysplastic syndromes, chronic myelomonocytic leukemia, and squamous cell carcinoma of the head and neck. Phase 3 is the highest phase of clinical development, indicating that Ceralasertib has progressed through earlier stages of testing and has shown promising results in terms of safety and efficacy. This phase involves large-scale clinical trials to further evaluate the drug's effectiveness and monitor any potential side effects. Phase II Clinical Trial of ATR Inhibitor: BerzosertibBerzosertib is a small molecule drug that targets the protein ATR. It is being developed for the treatment of various therapeutic areas including neoplasms, digestive system disorders, endocrinology and metabolic disease, respiratory diseases, and urogenital diseases. The drug is specifically indicated for neoplasms, small cell lung cancer, prostatic cancer, ovarian cancer, fallopian tube carcinoma, peritoneal neoplasms, solid tumors, and esophageal carcinoma. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. Berzosertib is being developed by Vertex Pharmaceuticals, Inc., a renowned originator organization in the pharmaceutical industry. Currently, the drug has reached Phase 2 of clinical development. This indicates that it has already undergone initial testing for safety and efficacy in a limited number of patients. One notable aspect of Berzosertib is its regulatory status as an orphan drug. Orphan drugs are medications developed to treat rare diseases or conditions that affect a small number of patients. This designation provides certain incentives to the pharmaceutical company, such as extended market exclusivity and financial support for research and development. Based on the available information, Berzosertib shows promise in the field of biomedicine. Its target, ATR, is involved in DNA damage response and repair, making it a potential candidate for the treatment of various types of cancer. The drug's active indications, including small cell lung cancer, prostatic cancer, and ovarian cancer, highlight its potential in addressing significant unmet medical needs in these areas. However, it is important to note that the information provided is limited, and further research and clinical trials are necessary to fully evaluate the safety and efficacy of Berzosertib. The drug's current phase of development suggests that it is still in the early stages of testing, and its ultimate success will depend on the results of future studies. In conclusion, Berzosertib is a small molecule drug developed by Vertex Pharmaceuticals, Inc. that targets ATR. It is being investigated for its potential in treating various neoplasms and has reached Phase 2 of clinical development. As an orphan drug, it holds promise for addressing unmet medical needs in rare diseases. However, additional research is needed to determine its safety and efficacy.

100 Deals associated with Berzosertib

External Link

KEGG	Wiki	ATC	Drug Bank
D11148	Berzosertib	-	DB11794

R&D Status

10 top R&D records.

to view more data

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 Healthcare KGaA	16 Sep 2021
Small Cell Lung Cancer	Phase 2	China	BSP Pharmaceuticals SpA	16 Sep 2021
Small Cell Lung Cancer	Phase 2	China	Merck Serono (Beijing) Pharmaceutical R&D Co., Ltd.	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	jenaklpaxd(nkqnxzsdan) = vzqeojalmt pkdilmexgi (otbmsvhcvr, twelmdhzar - yppxohkjaf) View more	-	29 Nov 2024
NCT05246111 (CTgov)	Phase 1	Advanced Malignant Solid Neoplasm	6	[14C]Berzosertib ([14C]Berzosertib)	kaxwbbnkwt(rqkuknwujj) = kttvfjqyru kbkimxhhvn (naehijfmwg, 3.2) View more	-	22 Nov 2024
				Berzosertib+Topotecan (Berzosertib + Topotecan)	zckiatpfng = sdxpzmboms rxykooyage (jhpfmanyon, ycwwgqgghm - uwvckijuyl) 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)	mcgctrknlk = fdwhjuldls lfcoyeszms (nshzgmkuph, osqycyubso - gpqaywxovg) View more	-	26 Sep 2024
				Berzosertib+Topotecan (Safety run-in Part (DL 1): Berzosertib 105 mg/m^2 + Topotecan 1.25 mg/m^2)	hbajmvqccw = saekqhcerg qyasgoxwgh (jjqltzjinb, eqdiojpelx - jgfkyogaou) View more
NCT03641547 (CHARIOT, Pubmed \| Br J Cancer) Manual	Phase 1	Esophageal Carcinoma \| Advanced Malignant Solid Neoplasm	34	Berzosertib with RT	rwwkexcfml(mrkmojjefl) = nodfanvsfh bhdbwkhomt (tnuhynlfkf ) View more	Positive	24 Feb 2024
				Berzosertib cisplatinlcapecitabineecitabine	rwwkexcfml(mrkmojjefl) = ipdnfyeens bhdbwkhomt (tnuhynlfkf ) View more
NCT02567409 (ASCO_GU2024) Manual	Phase 2	Advanced Urothelial Carcinoma	87	gemcitabine + cisplatin + berzosertib	lcbxqdkkes(vyhajhyroa) = eteiwpxoet oegbgrsoyw (wwhffgfrat ) View more	Negative	25 Jan 2024
				gemcitabine + cisplatin	lcbxqdkkes(vyhajhyroa) = ajmdchgnvv oegbgrsoyw (wwhffgfrat ) View more
NCT03896503 (Pubmed \| JAMA Oncol)	Phase 2	Small Cell Lung Cancer	60	Topotecan alone	kcjtdzsvav(llgxnjqjek) = bwjsklmccu lcldxhacmk (flbedwwmjn, 1.2 - 5.1) View more	Positive	01 Dec 2023
				Topotecan + Berzosertib	kcjtdzsvav(llgxnjqjek) = mwtbropuey lcldxhacmk (flbedwwmjn, 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))	tqvvlgprfh(ulpdjdrnsr) = fdthkuoavj hfhlizrawr (domxxcjzro, iebgussawg - kfstgswkcy) View more	-	17 Oct 2023
				Gemcitabine Hydrochloride+cisplatin (Arm B (Gemcitabine Hydrochloride, Cisplatin))	tqvvlgprfh(ulpdjdrnsr) = cltsrwmvbr hfhlizrawr (domxxcjzro, fcfnjvctxl - xbbhryoiru) View more
NCT03718091 (CTgov)	Phase 2	Solid tumor \| Advanced Malignant Solid Neoplasm \| Gastrointestinal Stromal Tumors ... View more	30	M6620 (Cohort T1: ATRX-mutant Leiomyosarcoma)	mtzyofoeay(ptwucgfinp) = ixlyjecnvu arhxnoehow (xnppoukaqy, awgelbprgl - ncwqrdlqwf) View more	-	07 Jul 2023
				M6620 (Cohort T2: Truncating ATM Mutation)	mtzyofoeay(ptwucgfinp) = qckwjqxawx arhxnoehow (xnppoukaqy, kkkgajwwyj - khukexfwmx) View more
NCT03641313 (ASCO 12023 \| ASCO 22023) Manual	Phase 2	Gastrooesophageal junction cancer TP53 Mutation	17	Irinotecan Hydrochloride+Berzosertib	khpchijrho(tbzrhawzhm) = duzcaaeqow rqrpamadmu (sgtxdehyrd ) View more	Negative	26 May 2023
NCT04826341 (AACR2023) Manual	Phase 1	Solid tumor ATM Mutation \| BRCA1 Mutation	-	sacituzumab govitecan+berzosertib	cmragpqucs(crxovuuwrt) = blivqfxljd rlquruywlo (sojzvvjalz ) View more	Positive	14 Apr 2023

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