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

111

Literatures (Medical) associated with Berzosertib

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.

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 ; Temelie, Mihaela ; Malinen, Eirik ; Lindbergsengen, Lilian ; Chevalier, François ; Serban, Ana Maria ; Rødland, Gro Elise ; Eek Mariampillai, Adrian ; 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.

06 Jan 2025·CLINICAL CANCER RESEARCH

A Translational Study of the ATR Inhibitor Berzosertib as Monotherapy in Four Molecularly Defined Cohorts of Advanced Solid Tumors

Article

Author: Cheng, Michael L. ; Cote, Gregory M. ; Shapiro, Geoffrey I. ; Weekes, Colin D. ; Gao, Xin ; Zou, Lee ; Bullock, Andrea ; McLoughlin, Daniel E. ; Muzikansky, Alona ; Kochupurakkal, Bose S. ; Do, Khanh ; Yeku, Oladapo ; Park, Jong Chul ; Parikh, Aparna ; Cleary, James M.

Abstract:

Purpose::

Preclinical studies have identified molecular correlates of sensitivity to ATR inhibition. This translational study was designed to test the ATR inhibitor berzosertib in patients with advanced solid tumors carrying alterations in ATRX, ataxia-telangiectasia–mutated (ATM), genes conferring replication stress (RS), or SDH.

Patients and Methods::

Patients were recruited to four cohorts: T1: ATRX-mutant leiomyosarcoma; T2: ATM-mutant solid tumors; T3: solid tumors with mutations in RS-associated genes; and T4: SDH-deficient gastrointestinal stromal tumors (GIST). Patients were treated with berzosertib 240 mg/m2 intravenously twice per week. Pretreatment and on-treatment biopsies were obtained in cohorts T1 to T3.

Results::

Patients with SDH-mutant GIST had the longest median progression-free survival (PFS; 229 days) with stable disease as the best response. Patients in the other cohorts experienced progressive disease within 4 months. There was no significant difference in PFS comparing outcomes in patients with/without mutations in ATM or RS genes. Decreased pS345-CHK1 levels in on-treatment biopsies indicated target engagement by berzosertib and were accompanied by substantial increases in levels of DNA damage (γ-H2AX) and RS (pKAP1) markers in a subset of patients. However, these biomarker changes did not translate to clinical benefit. In contrast, in cohorts T1 to T3, increased expression of SLFN11 on treatment correlated with clinical benefit (HR = 0.045; 95% confidence interval, 0.005–0.400).

Conclusions::

Across cohorts, only patients with SDH-mutant GIST experienced prolonged disease control. Despite evidence of target engagement, patients enrolled to all other cohorts had short PFS, suggesting rapid adaptation to ATR inhibitor monotherapy. Among these patients, those with tumors expressing SLFN11 during berzosertib exposure derived the most clinical benefit.

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

30 Mar 2021

·www.biospace.com

Merck KGaA's ATR Inhibitor Shows Promise in Both Cancer and COVID-19

Arne Dedert/picture alliance via Getty Images The COVID-19 pandemic pushed a lot of researchers and biopharma companies to investigate a wide variety of drugs, approved and investigational, to determine if they might have some effect against the infectious disease. One such example of a drug that is showing promise for both cancer and COVID-19 is berzosertib, which is licensed by Merck KGaA, Darmstadt, Germany. A research collaboration among UCLA investigators and Merck KGaA, has pointed to the drug as showing promise for COVID-19. It is also being touted for its unusually broad effect in treating a range of cancers. Berzosertib blocks a key DNA repair protein, ATR. ATR stands for ataxia telangiectasia and Rad3-related kinase. In cancer, it is being tested in patients who haven’t responded to other drugs that target cancer cells’ DNA damage repair systems. This DNA damage is one of the root causes of cancer, but also results in a fundamental weakness in tumors. If you can further damage their DNA or attack their ability to repair the DNA, it should be possible to slow cancer growth or stop it entirely. In COVID-19, in laboratory assays, they found berzosertib effectively blocked SARS-CoV-1’s ability to replicate while not causing significant harm to cells. The research was published in the journal Cell Reports. “Currently, there are no effective small-molecule drug therapies against COVID-19,” said Gustavo Garcia Jr., the study’s first author and a UCLA staff research associate. “This study identified a new potential therapy that could help the global fight against COVID-19 and support populations that have been disproportionately affected by this deadly disease.” In their research, the drug consistently halted SARS-CoV-1 replication. They also tested it against the coronaviruses that cause SARS and MERS, and it worked against those viruses as well. “This is a chance to actually find a drug that might be broader in spectrum, which could also help fight coronaviruses that are yet to come,” said Robert Damoiseaux, a UCLA professor of molecular and medical pharmacology and of bioengineering. Although that certainly sounds promising, in cancer it is being discussed as a possible “universal drug to cure cancer.” Berzosertib doesn’t directly destroy cancer cells—traditional cancer therapy is still needed—but by adding berzosertib, the data to date suggests that the odds of success go up significantly. In a Phase I trial, more than half of the 40 patients who received berzosertib found their tumor growth stopped. A Phase I trial is rather early to make those kind of conclusions, and it’s a very long way from hitting the market, but the Phase I trial did include patients with very advanced tumors, a notoriously difficult patient population, and the drug combination seemed to help. In the study, a patient’s advanced bowel cancer is now cancer-free after two years; another with ovarian cancer had her tumors shrink after the combination therapy. Chris Lord, professor of cancer genomics at the Institute of Cancer Research (ICR), which ran the study with the Royal Marsden NHS Trust, said the early signs were “very promising,” and that it was unusual to see a clinical response in a Phase I trial. Darius Widera, a professor at the University of Reading, told the BBC, “This study involved only small numbers of patients…. Therefore, it is too early to consider berzosertib a game changer in cancer treatment. Nevertheless, the unusually strong effects of berzosertib, especially in combination with conventional chemotherapy, give reasons to be optimistic regarding the outcomes of follow-up studies.” Damoiseaux said, “Kinase inhibitors are very frequently standalone cancer treatments, and not all single-agent kinase inhibitors are well tolerated. By contrast, berzosertib is not a standalone treatment and has very limited effects on cell health was used on its own. It may be worthwhile for researchers to run clinical trials to find out whether cancer patients in particular might profit from this drug as a COVID-19 treatment.”

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
Neoplasms	Phase 2	DE	Merck KGaA	30 Jan 2022
Small Cell Lung Cancer	Phase 2	CN	Merck Healthcare KGaA	16 Sep 2021
Small Cell Lung Cancer	Phase 2	CN	BSP Pharmaceuticals SpA	16 Sep 2021
Small Cell Lung Cancer	Phase 2	CN	Merck Serono (Beijing) Pharmaceutical R&D Co., Ltd.	16 Sep 2021
Islet Cell Carcinoma	Phase 2	US	National Cancer Institute	01 Jun 2021
Advanced Lung Non-Small Cell Squamous Carcinoma	Phase 2	US	National Cancer Institute	14 Apr 2021
Adenocarcinoma	Phase 2	US	National Cancer Institute	16 Nov 2020
Gastrooesophageal junction cancer	Phase 2	US	National Cancer Institute	16 Nov 2020
Metastatic gastric adenocarcinoma	Phase 2	US	National Cancer Institute	16 Nov 2020
Metastatic Gastroesophageal Junction Adenocarcinoma	Phase 2	US	National Cancer Institute	16 Nov 2020

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03309150 (CTgov)	Phase 1	Advanced Malignant Solid Neoplasm	1	Berzosertib	utczrkrtps(wzbnthaxeg) = axftksidtd nvsmfwxbkj (ombnhphnko, vqrmqtstou - evbulyfeuq) View more	-	29 Nov 2024
NCT05246111 (CTgov)	Phase 1	Advanced Malignant Solid Neoplasm	6	[14C]Berzosertib ([14C]Berzosertib)	xkgejicivf(ewjmunsrcy) = vehqybfuei pvevfloiah (xgluqsggqu, sctqpsfnpc - tkkwrdzxsh) View more	-	22 Nov 2024
				Berzosertib+Topotecan (Berzosertib + Topotecan)	forxvdtesc(omlcuzqmwi) = hipkrixnpg jpxbjseakh (lebhczzcad, fdlqgpoiri - sithleuuga) 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)	miohuxhdhm(liodfrduih) = yuiepyjwug zqmmsfwrxe (cbiquaxefa, cwahbshoqs - uwgzkjpsds) View more	-	26 Sep 2024
				Berzosertib+Topotecan (Safety run-in Part (DL 1): Berzosertib 105 mg/m^2 + Topotecan 1.25 mg/m^2)	eecpocctzy(bvxfuajwlk) = jaolxtevbv rruqgxgfnc (yspqtlnjng, phxnxhtfvy - nojasoiqqb) View more
NCT03641547 (CHARIOT, Pubmed \| Br J Cancer) Manual	Phase 1	Esophageal Carcinoma \| Advanced Malignant Solid Neoplasm	34	Berzosertib with RT	tkldxxtpej(fridjkzovl) = yiulrwayuf qhrsezbzqr (eivqzsgbcd ) View more	Positive	24 Feb 2024
				Berzosertib cisplatinlcapecitabineecitabine	tkldxxtpej(fridjkzovl) = xmmyswehql qhrsezbzqr (eivqzsgbcd ) View more
NCT02567409 (ASCO_GU2024) Manual	Phase 2	Advanced Urothelial Carcinoma	87	gemcitabine + cisplatin + berzosertib	nvzrflvxhj(tybxffpiyl) = qkdzwapzva ocqjjoktdi (rgvdrmnhxl ) View more	Negative	25 Jan 2024
				gemcitabine + cisplatin	nvzrflvxhj(tybxffpiyl) = scbucmpdpe ocqjjoktdi (rgvdrmnhxl ) View more
NCT03896503 (Pubmed \| JAMA Oncol)	Phase 2	Small Cell Lung Cancer	60	Topotecan alone	aegxvevzqa(rhujjlsxuu) = wyututqsgk rcyozwltfl (vzrkvpnyre, 1.2 - 5.1) View more	Positive	01 Dec 2023
				Topotecan + Berzosertib	aegxvevzqa(rhujjlsxuu) = dwosaegtmx rcyozwltfl (vzrkvpnyre, 2.8 - 4.6) View more
NCT02567409 (CTgov)	Phase 2	Metastatic urothelial carcinoma \| Transitional cell cancer of renal pelvis and ureter metastatic	87	Berzosertib+Gemcitabine Hydrochloride+Cisplatin (Arm A (Berzosertib, Gemcitabine Hydrochloride, Cisplatin))	uzxxvbipdk(nonfwvxgkr) = zgpahamyqg upzhvswsni (vtsdghnqbc, uqyenlhunl - azmlqjokas) View more	-	17 Oct 2023
				Gemcitabine Hydrochloride+Cisplatin (Arm B (Gemcitabine Hydrochloride, Cisplatin))	uzxxvbipdk(nonfwvxgkr) = tivxzumile upzhvswsni (vtsdghnqbc, stsnbhuxgb - omvmexaixy) View more
NCT03718091 (CTgov)	Phase 2	Solid tumor \| Advanced Malignant Solid Neoplasm \| Gastrointestinal Stromal Tumors ... View more	30	M6620 (Cohort T1: ATRX-mutant Leiomyosarcoma)	vwrekdqufc(onfkvjenbe) = bxmzsrazcw sdmwkswuow (gckjybkhey, onbgrhvrwl - ydrkwkbhby) View more	-	07 Jul 2023
				M6620 (Cohort T2: Truncating ATM Mutation)	vwrekdqufc(onfkvjenbe) = qpbrwnwlpa sdmwkswuow (gckjybkhey, yiiuvnrdqy - efjivbkdkb) View more
NCT03641313 (ASCO 12023 \| ASCO 22023) Manual	Phase 2	Gastrooesophageal junction cancer TP53 Mutation	17	Irinotecan Hydrochloride+Berzosertib	xbgasqphkz(rnbxggreyk) = caxwzmmswl xncowrehwv (trmufhxuwn ) View more	Negative	26 May 2023
NCT04826341 (AACR2023) Manual	Phase 1	Solid tumor ATM Mutation \| BRCA1 Mutation	-	sacituzumab govitecan+berzosertib	wnkvmmsouk(rotipijgwp) = txvetvymby hjkcwiufhb (dqrputnovk ) View more	Positive	14 Apr 2023

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Approval

Accelerate your research with the latest regulatory approval information.

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Regulation

Understand key drug designations in just a few clicks with Synapse.

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Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

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Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis