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

/ CompletedPhase 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

/ CompletedPhase 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

183

Literatures (Medical) associated with Berzosertib

01 May 2026·Cancer Reports

Combined Inhibition of ATR and Ribonucleotide Reductase Induces Synergistic Antineoplastic Activity in Osteosarcoma Cells

Article

Author: Till Milde ; Natalie Aderhold ; Bernd Gruhn ; Jürgen Sonnemann ; Sabine Becker ; Lisa Immesberger

ABSTRACT:

Background:

Osteosarcoma is the most common bone cancer in children and young adults. Its prognosis has not improved significantly since the introduction of the chemotherapy regimen established about 40 years ago, highlighting the need for new therapeutic strategies.

Aims:

The present study was undertaken to assess the effectiveness of combined inhibition of two promising drug targets, ATR and ribonucleotide reductase (RNR), in osteosarcoma cells.

Methods and Results:

The ATR inhibitor berzosertib and the RNR inhibitors triapine and didox were tested in TP53 wild‐type (U2OS, MG‐63) and mutant (SaOS‐2) osteosarcoma cell lines. Combination effects were examined by flow cytometric analysis of cell death, loss of the mitochondrial membrane potential and DNA fragmentation as well as by caspase 3/7 activity assay and real‐time RT‐PCR. The drug interactions were evaluated using combination index analysis. Single treatment with ATR or RNR inhibitors resulted in mild to moderate effects, whereas combined treatment resulted in strong and synergistic effects. ATR and RNR inhibitors cooperated to elicit loss of the mitochondrial membrane potential, to activate caspase 3/7 and to trigger DNA fragmentation, suggesting that the combination of ATR and RNR inhibitors induced an apoptotic form of cell death. The cytotoxic effects were independent of TP53 mutational status.

Conclusion:

Our study demonstrates that combined inhibition of ATR and RNR was effective in osteosarcoma cells. These in vitro findings offer support for investigating in vivo the potential of a combination of ATR and RNR inhibitors as a new treatment strategy for osteosarcoma.

15 Mar 2026·CANCER

A phase 1 study of berzosertib (M6620, VX‐970) in combination with cisplatin and radiation in patients with locally advanced head and neck squamous cell carcinoma (ETCTN 9950)

Article

Author: Jonathan W. Riess MD ; Yuji Zhang PhD ; Priyanka Bhateja MD ; Thomas H. Davis MD ; Conor E. Steuer MD ; Virginia Diavolitsis MD ; Aarti Bhatia MD, MPH ; Brian F. Kiesel PhD ; Moon Fenton MD, PhD ; Darrion L. Mitchell MD, PhD ; Jan H. Beumer PharmD, PhD, DABT ; Nabil F. Saba MD ; Michael Carducci MD ; Harold Tara MD ; Barbara Burtness MD ; Dan P. Zandberg MD ; Taofeek K. Owonikoko MD, PhD ; Zhengjia Chen PhD ; Varinder Kaur MD ; Justine Yang Bruce MD ; Dong M. Shin MD ; Malini Patel MD ; Garrett Wasp MD, MPH ; John C. Schmitz PhD ; Charles Kunos MD ; Susanne Arnold MD ; Steven D. Gore MD

ABSTRACT:

Background:

Ataxia telangiectasia Rad3‐related (ATR) protein kinase regulates DNA damage response and is essential for tumor cell survival. Preclinically, ATR inhibition can sensitize tumor cells to radiation and chemotherapy. The authors conducted a phase 1 trial of berzosertib, a selective ATR inhibitor, in combination with definitive radiation and cisplatin in locally advanced head and neck squamous cell cancers (LA‐HNSCC).

Methods:

LA‐HNSCC patients received daily radiation (2 Gy per fraction to 70 Gy) and weekly intravenous (iv) cisplatin 40 mg/m 2 . Berzosertib was administered (iv) once weekly, starting with a pharmacokinetic lead‐in dose. Three berzosertib dose levels (DL) were tested: 120 mg/m 2 (DL1), 160 mg/m 2 (DL2), and 200 mg/m 2 (DL3).

Results:

Forty‐one of 43 enrolled patients were evaluable for safety and preliminary efficacy assessments. Four patients experienced dose‐limiting toxicities (DLTs) in dose‐escalation: grade 4 thrombocytopenia (1), grade 4 respiratory failure (1), grade 3 renal injury and hypoxia (1), and inability to receive 90% of the planned radiation dose (1). DL3 was the recommended phase 2 dose, and 15 patients were enrolled at this DL as an expansion cohort. Objective response rates (ORR) in patient cohorts treated with any amount of berzosertib; treated with at least 50% of planned treatment; and in the expansion cohort were 78.8% (26 of 33), 78.8% (26 of 33), and 63.6% (7 of 11), respectively, after excluding eight inevaluable patients without post‐treatment imaging assessment.

Conclusions:

Berzosertib (200 mg/m 2 iv weekly) was safe when combined with chemoradiation but did not improve complete response rate in LA‐HNSCC.

05 Mar 2026·BRITISH JOURNAL OF CANCER

Targeting the DNA damage response prevents regrowth of colorectal peritoneal metastasis-derived organoids following treatment with mitomycin C

Article

Author: Borel Rinkes, Inne ; Stefan, Arianna ; Jansen, Anne M L ; Kranenburg, Onno ; Kieboom, Madelief ; van Megesen, Kyah ; Amico, Rebecca

Abstract:

Background:

A minority of Colorectal Cancer (CRC) patients with peritoneal metastases is eligible for cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC). However, recurrence rates are high (~80%). We tested whether inhibitors of the DNA damage response (DDR) could prevent recurrence in an in vitro HIPEC model.

Methods:

Peritoneal metastasis-derived organoids (PMDOs; n = 10) were treated with inhibitors of ATR (berzosertib, ceralasertib, elimusertib), CHK1 (rabusertib), and WEE1 (adavosertib) alone, and in combination with MMC, oxaliplatin, or irinotecan. Western blotting was used to determine Chk1 phosphorylation and markers of DNA damage. Microscopy and ATP quantification were used to measure the effects of (combination) treatments on cell viability and recurrence/regrowth.

Results:

All PMDOs displayed rapid regrowth (recurrence) following single-drug chemotherapy treatment. Berzosertib inhibited chemotherapy-induced CHK1 phosphorylation, augmented DNA damage, and abrogated recurrence in all 10 MMC-treated PMDOs. The combination with oxaliplatin and irinotecan was less effective. In vitro HIPEC with MMC, followed by ‘adjuvant’ treatment with any of the DDR inhibitors for 3 days, completely prevented PMDO recurrence.

Conclusions:

PMDOs can be completely eradicated if MMC treatment is followed by inhibition of ATR or other DDR kinases. DDR inhibitors may therefore have value in the adjuvant treatment of peritoneal metastases following CRS-HIPEC.

News (Medical) associated with Berzosertib

01 Jun 2026

·www.biospace.com

Callio Therapeutics to Present Phase 1 Trial Design of CLIO-8221, Novel Dual-Payload ADC, at ASCO 2026

SEATTLE and SINGAPORE, May 27, 2026 (GLOBE NEWSWIRE) -- Callio Therapeutics, a biotherapeutics company advancing dual-payload antibody-drug conjugates (ADCs) with a targeted, multi-mechanism approach to cancer treatment, today announced that it will present a trial-in-progress poster highlighting the Phase 1 trial design of CLIO-8221 at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting (May 29-June 2) in Chicago. CLIO-8221 is a first-in-class dual-payload ADC currently in Phase 1 clinical development ( NCT07300943 ) for HER2-expressing solid tumors. “CLIO-8221 is the first program from Callio Therapeutics’ dual-payload ADC pipeline to enter the clinic, advancing our strategy to develop rationally designed payload combinations for hard-to-treat tumors,” said Naomi Hunder, MD, Chief Medical Officer of Callio Therapeutics. “Developed with our proprietary linker technology and payload combination platform, CLIO-8221 is a first-in-class dual-payload ADC designed to deliver a topoisomerase 1 inhibitor and an ATR inhibitor directly to HER2-expressing tumors to address key mechanisms of resistance to existing HER2-targeted ADCs, including trastuzumab deruxtecan. With our Phase 1 trial now enrolling patients with advanced HER2-expressing solid tumors, we look forward to generating clinical data that will inform its potential as a differentiated treatment option.” “Patients with HER2-expressing solid tumors who progress on currently available HER2-targeted therapies continue to have limited treatment options,” said Timothy A. Yap, MBBS, PhD, lead investigator at The University of Texas MD Anderson Cancer Center for the CLIO-8221 Phase 1 trial, and presenting author of the poster. “CLIO-8221 represents an innovative dual-payload approach to overcome resistance associated with existing HER2-targeted ADCs. This trial marks an important step in evaluating whether combining topoisomerase 1 and ATR inhibition within a single HER2-targeted ADC can expand treatment possibilities for patients with HER2-expressing solid tumors.” The Phase 1 clinical trial recruitment is ongoing in Australia and the United States, and the company plans to activate sites in China. At ASCO, Callio Therapeutics will present previously disclosed preclinical data (AACR 2026) that support the therapeutic potential of CLIO-8221 and the Phase 1 trial design: By simultaneously delivering a topoisomerase 1 inhibitor (exatecan) and an ATR inhibitor (berzosertib), CLIO-8221 drives direct tumor cell killing at doses that also support a robust bystander effect, achieving superior in vivo efficacy compared to single-payload ADCs CLIO-8221 demonstrated potent anti-tumor activity across varying HER2 expression levels and drove tumor regression after a single dose in both trastuzumab deruxtecan-sensitive and -insensitive models CLIO-8221 exhibited a highly favorable safety profile; it was well-tolerated in non-human primates with no significant adverse effects observed at doses of 70 mg/kg (highest dose tested), establishing a No-Observed-Adverse-Effect Level (NOAEL) significantly higher than that of trastuzumab deruxtecan Phase 1 of the study is a dose escalation with optional dose level expansions, and dose escalation may enroll across HER2-expressing cancers, including cancers that did not respond to or relapsed after trastuzumab deruxtecan treatment Presentation details: Poster/Abstract Title: Phase 1/2 Study of CLIO-8221, a HER2-targeted, dual-payload exatecan and ATR inhibitor antibody-drug conjugate (ADC) in patients with advanced HER2-expressing solid tumors Poster Session : Developmental Therapeutics – Molecularly Targeted Agents and Tumor Biology Date & Time : May 30, 2026, 1:30 PM - 4:30 PM CDT Location: McCormick Place, Hall A – Posters and Exhibits Presenter : Timothy A. Yap, MBBS, PhD, The University of Texas MD Anderson Cancer Center Abstract Number: TPS3162 Poster Board: 295b The full abstract is available on the ASCO Annual Meeting website. The poster will be available on the ASCO website on May 30, 2026. About CLIO-8221 HER2 is a clinically validated target for antibody-drug conjugates (ADCs), with multiple approved therapies demonstrating meaningful benefit across tumor types, however, most patients eventually progress on treatment despite retaining HER2 expression. Mechanistic resistance to cytotoxic payloads has emerged as a key reason for treatment failure. CLIO-8221 is a novel, first-in-class dual-payload ADC targeting HER2, designed to address this challenge. CLIO-8221 delivers two mechanistically complementary payloads, a topoisomerase 1 (Topo1) inhibitor and an ATR inhibitor, directly to HER2-expressing tumors. While Topo1 inhibitors have shown strong clinical activity, activation of the DNA damage response following Topo1 inhibitor-induced replication stress represents a potential major driver of resistance. By simultaneously inhibiting Topo1 and blocking the DNA damage response through ATR inhibition, CLIO-8221 is engineered to overcome payload insensitivity and sensitize tumors to Topo1 inhibition. Developed using proprietary linker and ADC platform technologies, CLIO-8221 aims to maximize anti-tumor activity while reducing systemic toxicity, offering the potential for deeper and more durable responses in patients who have progressed on existing HER2-targeted therapies. About Callio Therapeutics Callio Therapeutics is a clinical‑stage company engineering oncology-focused dual-payload ADCs for the next frontier of targeted cancer therapy. Powered by a proprietary platform featuring adaptable, modular linker technology, Callio Therapeutics is developing a focused pipeline of dual-payload ADCs engineered with rational, synergistic payload combinations matched to specific tumor biology and to counter multiple mechanisms of resistance. CLIO-8221, the company’s lead candidate, is a HER2-targeted dual-payload ADC currently being evaluated in a Phase 1 clinical trial. Callio Therapeutics is built on technology and programs licensed from Hummingbird Bioscience, an AI-enabled biotherapeutics company and R&D collaborator. Headquartered in Seattle and Singapore, and backed by top life science investors, Callio Therapeutics is built to discover and deliver, with an experienced team with a track record of success. For more information, visit and follow Callio Therapeutics on LinkedIn. Contacts Media: Crystal Ho media@calliotx.com Ally Stubin – ICR Healthcare Ally.Stubin@ICRHealthcare.com (646) 667-1861 Investors: ir@calliotx.com Stephanie Carrington – ICR Healthcare stephanie.carrington@ICRHealthcare.com (646) 277-1282

Phase 1ASCOADCAACR

29 Apr 2025

·endpts.com

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

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

Clinical ResultPhase 3Phase 2

10 Apr 2024

·www.prnewswire.com

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

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

AACR

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
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
Metastatic Gastroesophageal Junction Adenocarcinoma	Phase 2	United States	National Cancer Institute	16 Nov 2020
Extensive stage Small Cell Lung Cancer	Phase 2	United States	National Cancer Institute	30 Dec 2019

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04266912 (ASCO2026)	Phase 1/2	HPV+ \| MSH2 mutation \| somatic RAD51 mutation	17	Berzosertib + Avelumab	llzpkdfmvh(ueptpncbju) = ibplaemrqr cyqjzsnppi (rmrhpfknuu ) View more	Positive	29 May 2026
NCT02627443 (2022-RA-464-ESGO, CTgov)	Phase 1	Platinum-sensitive epithelial ovarian cancer \| Primary peritoneal carcinoma \| Recurrent ovarian cancer ... View more	35	VX-970+CARBOplatin+gemcitabine (Dose Level 1)	obbwudvfqy = rwkhqmxssh pqhoaruryo (ltyurjnifo, ndpmbpudnq - gsevbwdhle) View more	-	02 Apr 2026
				VX-970+CARBOplatin+gemcitabine (Dose Level 2)	obbwudvfqy = fghtszfcuq pqhoaruryo (ltyurjnifo, yadnaecdwi - xrqfqyhfvv) View more
NCT04216316 (ETCTN 10313, CTgov)	Phase 1/2	Advanced Lung Non-Small Cell Squamous Carcinoma	12	Berzosertib (M6620)+Carboplatin+Gemcitabine+Pembrolizumab (Dose Level -1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab))	wkifauzpib = gsydlioyqt tualqcyamq (uutdxkqrth, pgtzieqrxq - jdhvlclofh) View more	-	24 Mar 2026
				Berzosertib (M6620)+Carboplatin+Gemcitabine+Pembrolizumab (Dose Level 1 (Berzosertib (M6620) + Carboplatin + Gemcitabine + Pembrolizumab))	wkifauzpib = opadcjrkno tualqcyamq (uutdxkqrth, ubozekwfwl - fklnzwgnot) View more
NCT04768296 (DDRiver SCLC 250, Pubmed) Manual	Phase 2	Extensive stage Small Cell Lung Cancer \| Small Cell Lung Cancer	73	Berzosertib + topotecan	acmgmkctpj(gvbffqnjqt) = ytwnjroaph lureliqrbz (cqhqqssztw ) View more	Negative	19 Dec 2025
NCT03641313 (NCI 10211, Pubmed \| Oncologist)	Phase 2	Malignant neoplasm of gastro-oesophageal junction TP53 Mutant	17	Berzosertib + Irinotecan	ulzclvjavk(vtcnsthjtb) = rvvrenxpyx evjkvomist (aukjqjuguu ) View more	Negative	01 Dec 2025
NCT04216316 (ETCTN 10313, Pubmed \| Oncologist)	Phase 1	Squamous non-small cell lung cancer First line	12	Berzosertib 135 mg/m2, carboplatin AUC 5, gemcitabine 800 mg/m2 and pembrolizumab 200 mg	ovhmthgjod(kkzglalhrs) = Berzosertib 135 mg/m2, carboplatin AUC 4, gemcitabine 800 mg/m2 and pembrolizumab 200 mg zjbqmisvpt (tfxuehsyij ) View more	Positive	11 Nov 2025
NCT04266912 (CTgov)	Phase 1/2	Refractory Malignant Solid Neoplasm \| Metastatic Solid Tumor \| Advanced Malignant Solid Neoplasm ... View more	23	Berzosertib+Avelumab (Escalation Dose Level 1)	loszddkaka = mklyqembza cjolsiqxhc (gihzkxfvje, fpfzdszaph - xpkjfxsinf) View more	-	20 Oct 2025
				Berzosertib+Avelumab (Escalation Dose Level 2)	loszddkaka = fvubadifwq cjolsiqxhc (gihzkxfvje, uofxldvztf - asgkgkrkgy) View more
NCT02567422 (CTgov)	Phase 1	Squamous cell carcinoma of the oral cavity \| Squamous Cell Carcinoma of the Oropharynx \| Squamous cell carcinoma of the hypopharynx ... View more	43	M6620+cisplatin (Dose Level 1)	jxxzjybviu = atwhrzxivb hdmnacsfdc (ulebxazxwu, jnywbnpwux - vxdrfhqzce) View more	-	27 Jun 2025
				M6620+cisplatin (Dose Level 2)	jxxzjybviu = hscyvjbbue hdmnacsfdc (ulebxazxwu, abvbztmbma - ptabwuzjou) View more
NCT03517969 (CTgov)	Phase 2	Metastatic castration-resistant prostate cancer	73	Laboratory Biomarker Analysis+Carboplatin+Docetaxel (Arm A (Docetaxel, Carboplatin))	jfmgoswvkh = xlhhcypezr ksaslfdyrg (ykttgwlzot, drbpnnheki - xugntomeel) View more	-	08 May 2025
				Laboratory Biomarker Analysis+Berzosertib+Carboplatin (Arm B (Carboplatin, Berzosertib))	jfmgoswvkh = kfcxsvgfta ksaslfdyrg (ykttgwlzot, qkgimjvvuq - lnwjshmiir) View more
NCT03309150 (CTgov)	Phase 1	Advanced Malignant Solid Neoplasm	1	Berzosertib	mzulaarewu(ghihxllsxo) = jejsjktxua rvhskdqzqj (qmezygxwpi, wfrqivldiz - dkjpnjhpwg) View more	-	29 Nov 2024

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