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 will be conducted in two periods, Period 1 (mass balance) and Period 2 (extension). The purpose of Period 1 of this study is 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 is 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 / SuspendedPhase 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

Literatures (Medical) associated with Berzosertib

31 Dec 2023·Journal of enzyme inhibition and medicinal chemistry

Inhibitors of phosphoinositide 3-kinase (PI3K) and phosphoinositide 3-kinase-related protein kinase family (PIKK)

Review

Author: Heger, Zbynek ; Adam, Vojtech ; Nepovimova, Eugenie ; Kuca, Kamil ; Wu, Qinghua ; Valko, Marian ; Huang, Xueqin ; Korabecny, Jan ; Psotka, Miroslav ; Malinak, David ; You, Li ; Sivak, Ladislav

Phosphoinositide 3-kinases (PI3K) and phosphoinositide 3-kinase-related protein kinases (PIKK) are two structurally related families of kinases that play vital roles in cell growth and DNA damage repair. Dysfunction of PIKK members and aberrant stimulation of the PI3K/AKT/mTOR signalling pathway are linked to a plethora of diseases including cancer. In recent decades, numerous inhibitors related to the PI3K/AKT/mTOR signalling have made great strides in cancer treatment, like copanlisib and sirolimus. Notably, most of the PIKK inhibitors (such as VX-970 and M3814) related to DNA damage response have also shown good efficacy in clinical trials. However, these drugs still require a suitable combination therapy to overcome drug resistance or improve antitumor activity. Based on the aforementioned facts, we summarised the efficacy of PIKK, PI3K, and AKT inhibitors in the therapy of human malignancies and the resistance mechanisms of targeted therapy, in order to provide deeper insights into cancer treatment.

01 Dec 2023·JAMA oncology

Berzosertib Plus Topotecan vs Topotecan Alone in Patients With Relapsed Small Cell Lung Cancer

Article

Author: Redon, Christophe E ; Desai, Parth ; Ruiz, Jimmy ; Pommier, Yves ; Hao, Zhonglin ; Nieva, Jorge ; Shimellis, Hirity ; Nichols, Samantha ; Fuld, Alexander D ; Goyal, Shubhank ; Villaruz, Liza C ; Abel, Melissa ; Graham, Chante ; Sciuto, Linda ; McGlone, Jessie ; Mamdani, Hirva ; Kattappuram, Robbie ; Schroeder, Brett ; Thomas, Anish ; Chauhan, Aman ; Gore, Steven D ; Riess, Jonathan W ; Petty, W Jeffrey ; Pachecho, Jose M ; Kumar, Rajesh ; Sharma, Ajit Kumar ; Shelat, Meenakshi ; Schultz, Christopher W ; Pinkiert, Danielle ; Upadhyay, Deep ; Vilimas, Rasa ; Takahashi, Nobuyuki ; Malin, Justin ; Krishnamurthy, Manan ; Zhang, Jun ; Steinberg, Seth M ; Shum, Elaine ; Aladjem, Mirit I

Importance:

Patients with relapsed small cell lung cancer (SCLC), a high replication stress tumor, have poor prognoses and few therapeutic options. A phase 2 study showed antitumor activity with the addition of the ataxia telangiectasia and Rad3-related kinase inhibitor berzosertib to topotecan.

Objective:

To investigate whether the addition of berzosertib to topotecan improves clinical outcomes for patients with relapsed SCLC.

Design, Setting, and Participants:

Between December 1, 2019, and December 31, 2022, this open-label phase 2 randomized clinical trial recruited 60 patients with SCLC and relapse after 1 or more prior therapies from 16 US cancer centers. Patients previously treated with topotecan were not eligible.

Interventions:

Eligible patients were randomly assigned to receive topotecan alone (group 1), 1.25 mg/m2 intravenously on days 1 through 5, or with berzosertib (group 2), 210 mg/m2 intravenously on days 2 and 5, in 21-day cycles. Randomization was stratified by tumor sensitivity to first-line platinum-based chemotherapy.

Main Outcomes and Measures:

The primary end point was progression-free survival (PFS) in the intention-to-treat population. Secondary end points included overall survival (OS) in the overall population and among patients with platinum-sensitive or platinum-resistant tumors. The PFS and OS for each treatment group were estimated using the Kaplan-Meier method. The log-rank test was used to compare PFS and OS between the 2 groups, and Cox proportional hazards models were used to estimate the treatment hazard ratios (HRs) and the corresponding 2-sided 95% CI.

Results:

Of 60 patients (median [range] age, 59 [34-79] years; 33 [55%] male) included in this study, 20 were randomly assigned to receive topotecan alone and 40 to receive a combination of topotecan with berzosertib. After a median (IQR) follow-up of 21.3 (18.1-28.3) months, there was no difference in PFS between the 2 groups (median, 3.0 [95% CI, 1.2-5.1] months for group 1 vs 3.9 [95% CI, 2.8-4.6] months for group 2; HR, 0.80 [95% CI, 0.46-1.41]; P = .44). Overall survival was significantly longer with the combination therapy (5.4 [95% CI, 3.2-6.8] months vs 8.9 [95% CI, 4.8-11.4] months; HR, 0.53 [95% CI, 0.29-0.96], P = .03). Adverse event profiles were similar between the 2 groups (eg, grade 3 or 4 thrombocytopenia, 11 of 20 [55%] vs 20 of 40 [50%], and any grade nausea, 9 of 20 [45%] vs 14 of 40 [35%]).

Conclusions and Relevance:

In this randomized clinical trial, treatment with berzosertib plus topotecan did not improve PFS compared with topotecan therapy alone among patients with relapsed SCLC. However, the combination treatment significantly improved OS.

Trial Registration:

ClinicalTrials.gov Identifier: NCT03896503

01 Dec 2023·Investigational new drugs

The ATR inhibitor berzosertib acts as a radio- and chemosensitizer in head and neck squamous cell carcinoma cell lines

Article

Author: Brkic, Faris F ; Schnoell, Julia ; Heiduschka, Gregor ; Kadletz-Wanke, Lorenz ; Sparr, Carmen ; Jank, Bernhard J ; Haas, Markus ; Al-Gboore, Sega

Abstract:

Alterations in the DNA damage response play a crucial role in radio- and chemoresistance of neoplastic cells. Activation of the Ataxia telangiectasia and Rad3-related (ATR) pathway is an important DNA damage response mechanism in head and neck squamous cell carcinoma (HNSCC). Berzosertib, a selective ATR inhibitor, shows promising radio- and chemosensitizing effects in preclinical studies and is well tolerated in clinical studies. The aim of this study was to elucidate the effect of berzosertib treatment in combination with radiation and cisplatin in HNSCC. The HNSCC cell lines Cal-27 and FaDu were treated with berzosertib alone and in combination with radiation or cisplatin. Cell viability and clonogenic survival were evaluated. The effect of combination treatment was evaluated with the SynergyFinder or combination index. Apoptosis was assessed via measurement of caspase 3/7 activation and migration was evaluated using a wound healing assay. Berzosertib treatment decreased cell viability in a dose-dependent manner and increased apoptosis. The IC50 of berzosertib treatment after 72 h was 0.25–0.29 µM. Combination with irradiation treatment led to a synergistic increase in radiosensitivity and a synergistic or additive decrease in colony formation. The combination of berzosertib and cisplatin decreased cell viability in a synergistic manner. Additionally, berzosertib inhibited migration at high doses. Berzosertib displays a cytotoxic effect in HNSCC at clinically relevant doses. Further evaluation of combination treatment with irradiation and cisplatin is strongly recommended in HNSCC patients as it may hold the potential to overcome treatment resistance, reduce treatment doses and thus mitigate adverse events.

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	-	-	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	Merck Serono (Beijing) Pharmaceutical R&D Co., Ltd.	16 Sep 2021
Small Cell Lung Cancer	Phase 2	CN	BSP Pharmaceuticals SpA	16 Sep 2021
Islet Cell Carcinoma	Phase 2	US	National Cancer Institute	01 Jun 2021
Advanced Malignant Solid Neoplasm	Phase 2	US	The University of Texas MD Anderson Cancer Center	17 Mar 2020
Metastatic Solid Tumor	Phase 2	US	The University of Texas MD Anderson Cancer Center	17 Mar 2020
Refractory Malignant Solid Neoplasm	Phase 2	US	The University of Texas MD Anderson Cancer Center	17 Mar 2020
Unresectable Malignant Solid Neoplasm	Phase 2	US	The University of Texas MD Anderson Cancer Center	17 Mar 2020
Extensive stage Small Cell Lung Cancer	Phase 2	US	National Cancer Institute	30 Dec 2019

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


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))	bpqwuzqdox(xazfbhtiiw) = zezoohdqvm uhgtokldje (uekscyoczm, ehsihdqkal - boqluwpklv) View more	-	17 Oct 2023
NCT02567409 (CTgov)	Phase 2		87	Gemcitabine Hydrochloride+cisplatin (Arm B (Gemcitabine Hydrochloride, Cisplatin))	bpqwuzqdox(xazfbhtiiw) = qydnckqwoi uhgtokldje (uekscyoczm, tbtbroqhbn - epeaccyrba) View more	-	17 Oct 2023
NCT03718091 (CTgov)	Phase 2	Solid tumor \| Leiomyosarcoma \| Osteosarcoma	30	M6620 (Cohort T1: ATRX-mutant Leiomyosarcoma)	ndmsyuhwqq(itrgjquxfk) = dmvcdpnyvo olziiufhmb (vsowvpmbbg, jjtfxhdqxk - rdiidgnjih) View more	-	07 Jul 2023
NCT03718091 (CTgov)	Phase 2	Solid tumor \| Leiomyosarcoma \| Osteosarcoma	30	M6620 (Cohort T2: Truncating ATM Mutation)	ndmsyuhwqq(itrgjquxfk) = ikxhumtmzu olziiufhmb (vsowvpmbbg, fiszpdwudy - hlzmcxetap) View more	-	07 Jul 2023
NCT03641313 (ASCO2023) Manual	Phase 2	Gastrooesophageal junction cancer TP53 Mutation	17	Irinotecan Hydrochloride+Berzosertib	kejsiaprkl(oggeflbmso) = venxgicqpt uzwaubapme (jxxvubmyom ) View more	Negative	26 May 2023
NCT04826341 (AACR2023) Manual	Phase 1	Solid tumor ATM Mutation \| BRCA1 Mutation	-	sacituzumab govitecan+berzosertib	jtjxeecndc(irvyapudms) = auuwwxkkkl sajrcefqli (cwgpxxspoo ) View more	Positive	14 Apr 2023
NCT02595892 (NCI-9944 \| NCI CTEP: 9944, CTgov)	Phase 2	Recurrent Platinum-Resistant Primary Peritoneal Carcinoma \| Ovarian Serous Tumor \| Recurrent ovarian cancer ... View more	70	Gemcitabine Hydrochloride (Arm I (Gemcitabine Hydrochloride))	pckliwaowg(snmxfljnhw) = hfupksrdmo amzqcifjdv (ycewbfsgwt, jaguebgcpx - okgpfjaeey) View more	-	25 Oct 2022
NCT02595892 (NCI-9944 \| NCI CTEP: 9944, CTgov)	Phase 2		70	Berzosertib+Gemcitabine Hydrochloride (Arm II (Gemcitabine, ATR Kinase Inhibitor M6620))	pckliwaowg(snmxfljnhw) = wljaxoktji amzqcifjdv (ycewbfsgwt, zjxlorjnyb - nigrlvwhhi) View more	-	25 Oct 2022
NCT02627443 (2022-RA-464-ESGO, ESGO2022)	Phase 1	Platinum-Sensitive Fallopian Tube Carcinoma	-	Carboplatin	ekfhpgoccr(eptebhlosx) = The most common adverse events were cytopenias (96% grade 3â4 hematologic adverse event) btfoqeppan (zpdvtdkwyc )	Negative	20 Oct 2022
NCT03641547 \| EUCTR2015-003965-27-GB (CHARIOT, ESMO2022) Manual	Phase 1	Neoplasms	18	cisplatin+capecitabine+Berzosertib	wuhjsddglv(ndndoxlsix) = Berzosertib 140mg/m2 once weekly vhcgcduoin (okepwxbepf ) View more	Positive	10 Sep 2022
NCT02567422 (ESMO2022) Manual	Phase 1	Locally Advanced Head and Neck Squamous Cell Carcinoma	39	cisplatin+M6620+XRT	fhjjlytylb(phztsxdfld) = eiwmlrhqzi lklfewfmvw (sgzidnuvav ) View more	Positive	10 Sep 2022
NCT04768296 (DDRiver SCLC 250, ESMO2022) Manual	Phase 2	Small cell lung cancer recurrent \| Small Cell Carcinoma	6	Berzosertib 105 mg/m2+Topotecan 1.25 mg/m2 (solid tumours)	uqdfokrhfk(faczlwlcbp) = vaamocjnai qkapbcwtxc (iyuijcqlyx ) View more	Positive	10 Sep 2022
NCT04768296 (DDRiver SCLC 250, ESMO2022) Manual	Phase 2	Small cell lung cancer recurrent \| Small Cell Carcinoma	6	Berzosertib 210 mg/m2+Topotecan 1.25 mg/m2 ( pt-resistant SCLC)	uqdfokrhfk(faczlwlcbp) = jzjtovkmkz qkapbcwtxc (iyuijcqlyx ) View more	Positive	10 Sep 2022
NCT02595931 (ASCO2022) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	51	Irinotecan+Berzosertib	iarqarrlaj(makvprtxda) = Berzosertib 270 mg/m2 - irinotecan 180 mg/m2 was declared the RP2D. izlqcyqbrp (ccgxiokzxe ) View more	Positive	02 Jun 2022

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