elimusertib (BAY 1895344) / Bayer - LARVOL DELTA

Targeting the DNA damage response prevents regrowth of colorectal peritoneal metastasis-derived organoids following treatment with mitomycin C. (EACR 2025) - "We tested whether inhibitors of the DNA damage response (DDR) could prevent recurrence in an in vitro HIPEC model.Material and 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. 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."

Colorectal Cancer • Oncology • Solid Tumor • CHEK1

Injectable thermosensitive hydrogel co-loading with ATRi and doxorubicin for the treatment of triple-negative breast cancer. (PubMed, RSC Adv) - "Herein, we developed an injectable thermosensitive hydrogel for localized co-delivery of ATRi-BAY-1895344 (BAY) and doxorubicin (DOX), serving as a localized drug depot to minimize systemic toxicity while ensuring sustained tumor-specific drug release exceeding 4 days. This dual-action strategy overcomes chemo-resistance by disabling DDR compensatory mechanisms and prolongs tumor suppression through controlled drug release. The hydrogel platform represents a functional innovation in localized combination therapy, integrating stimuli-responsive drug delivery with DDR pathway disruption for synergistic efficacy."

Journal • Ataxia • Breast Cancer • Immunology • Movement Disorders • Oncology • Primary Immunodeficiency • Solid Tumor • Triple Negative Breast Cancer • ATR

Phase Ib basket expansion trial and alternative-schedule dose-escalation study of ATR inhibitor elimusertib in advanced solid tumors with DNA damage response defects. (PubMed, Cancer Discov) - "There was no association between ATM protein loss or ATM alterations and progression-free survival or overall response. Further studies to define optimal predictive biomarkers for ATR inhibitors as monotherapy and in combination are ongoing."

Journal • P1 data • Breast Cancer • Gynecologic Cancers • Hematological Disorders • Oncology • Solid Tumor • ATM

Testing the Addition of an Anti-cancer Drug, BAY 1895344, to the Usual Chemotherapy Treatment (Cisplatin, or Cisplatin and Gemcitabine) for Advanced Solid Tumors With Emphasis on Urothelial Cancer (clinicaltrials.gov) - P1 | N=74 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jun 2025 ➔ Jun 2026 | Trial primary completion date: Jun 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Biliary Cancer • Biliary Tract Cancer • Breast Cancer • Cervical Cancer • Cholangiocarcinoma • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Genito-urinary Cancer • Head and Neck Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Penile Cancer • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • Urothelial Cancer • ER • HER-2 • PGR

Testing the Addition of an Anti-cancer Drug, Elimusertib (BAY 1895344) ATR Inhibitor, to the Chemotherapy Treatment (Gemcitabine) for Advanced Pancreatic and Ovarian Cancer, and Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=14 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial primary completion date: Oct 2024 ➔ Apr 2025

Platinum resistant • Trial primary completion date • Fallopian Tube Cancer • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Pancreatic Adenocarcinoma • Pancreatic Cancer • Peritoneal Cancer • Solid Tumor

Comparative in vivo toxicology of ATR inhibitors ceralasertib, elimusertib, and berzosertib alone and in combination with ionizing radiation. (PubMed, Toxicol Appl Pharmacol) - "Cardiotoxicity was observed following single-dose ceralasertib, but no other ATRi, possibly due to high unbound plasma drug concentrations. Our results further support and guide clinical development of ATRi in clinic."

Journal • Preclinical • Ataxia • Cardiovascular • Immunology • Movement Disorders • Oncology • Primary Immunodeficiency

Testing the Addition of an Anti-cancer Drug, Elimusertib (BAY 1895344) ATR Inhibitor, to the Chemotherapy Treatment (Gemcitabine) for Advanced Pancreatic and Ovarian Cancer, and Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=14 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | N=64 ➔ 14 | Trial completion date: Feb 2025 ➔ May 2026 | Trial primary completion date: Feb 2025 ➔ Oct 2024

Enrollment change • Trial completion date • Trial primary completion date • Fallopian Tube Cancer • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Pancreatic Adenocarcinoma • Pancreatic Cancer • Peritoneal Cancer • Solid Tumor

YF550 is a potent and selective inhibitor of KIF18A, specifically targeting CIN+ cancer cells (AACR 2025) - "In contrast to the Eg5 inhibitor Ispinesib, YF550 does not inhibit normal PBMC proliferation...YF550 has demonstrated synergistic effects when combined with various agents, including Olaparib (PARP inhibitor), PF-07104091 (CDK2 inhibitor), Elimusertib (ATR inhibitor), Volasertib (PLK1 inhibitor), and MMAE, in cellular proliferation assays. In the OVCAR3 ovarian cancer xenograft model, YF550 has shown superior efficacy compared to KIF18A inhibitor AMG650 at a 5 mg/kg dose, with no significant impact on body weight. Furthermore, YF550 induced tumor regression in both the OVCAR8 ovarian and JIMT-1 HER2 positive breast cancer xenograft models. YF550 exhibits superior ADME and PK property suitable for clinical development for CIN+ cancers with high aneuploidy score and has the potential for combination therapy with PD-1/L1 antibodies, PARP1 inhibitors, and MMAE based ADC."

IO biomarker • Late-breaking abstract • Breast Cancer • Head and Neck Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • HER-2 • KIF18A

Efficacy of ATR kinase inhibitor elimusertib monotherapy or combination in tumors with DNA damage response pathway and other genomic alterations. (PubMed, Mol Cancer Ther) - "The combination of the PI3K inhibitor copanlisib with elimusertib enhanced EFS-2 compared to monotherapy in 3 of 11 models tested. The combination of elimusertib with the poly (ADP-ribose) polymerase (PARP) inhibitor niraparib enhanced antitumor activity compared to single agents in PARP-resistant PDX models. Our study shows that ATR inhibition has antitumor activity, including in models with both intrinsic and acquired PARP inhibitor resistance. Further work is needed to better refine patient selection for ATR-based therapies."

Journal • Monotherapy • Ataxia • Immunology • Movement Disorders • Oncology • Primary Immunodeficiency • ATM • BRCA1 • BRCA2

Investigating genes and pathways determining sensitivity or resistance to anti-L1cam ADCs in lymphomas (AACR 2025) - "LOF and GOF CRISPR-Cas9 screenings identified genes related to resistance or sensitivity to anti-L1CAM ADCs that could be potentially used as therapeutic targets or biomarkers."

IO biomarker • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • Solid Tumor • T Cell Non-Hodgkin Lymphoma • ABCB1 • ARID1A • CASP9 • CD20 • CDKN2B • CHD4 • FBXW7 • L1CAM • MAPK9 • RAD51B • RIF1 • RIPK1 • SOX11 • TP53

Morphology-guided classification of oral cancer using patient-derived organoids and its therapeutic implications (AACR 2025) - "As a result of evaluating 14 drugs by organoid subtype in a high-throughput drug evaluation system using a 384-well plate, normal-like or grape-like organoids showed a good response to single drug treatment. We observed that dense organoids, which exhibited resistant responses to single drugs, showed an increased synergistic effect when co-treated with the first-line standard chemotherapy drug, cisplatin, and the ATR inhibitor (bay1895344), compared to other subtypes."

Clinical • Tumor mutational burden • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • TMB

Harnessing a radiation-resistant organoid platform to propose novel strategies for precision treatment of advanced oral cancer (AACR 2025) - "The ATR inhibitor, BAY1895344, demonstrated synergistic effects...This study aims to address the limitations of existing preclinical models by utilizing patient-derived organoids that preserve tumor heterogeneity, thereby providing a platform and treatment prediction for clinically relevant research. These findings are anticipated to contribute significantly to the development of precision medicine-based therapeutic strategies for advanced oral cancer."

Metastases • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Unveiling markers of response to ATR inhibitor and TMZ combinations in rare tumor PDXs (AACR 2025) - "The combination of ATR inhibitors with temozolomide (TMZ) [ATRi+TMZ] enhances the cytotoxic effects of TMZ by targeting DNA damage response pathways, particularly in cancer cells with impaired DNA repair mechanisms, offering a promising therapeutic strategy for tumors resistant to conventional treatments. This study utilized gene expression profiling of 38 rare tumor patient-derived xenograft (PDX) models available in the NCI Patient-Derived Models Repository (PDMR) (https://pdmr.cancer.gov) to identify potential biomarkers that predict responses to TMZ combined with either of two ATR inhibitors, i.e., AZD6738 (Ceralasertib) and BAY1895344 (Elimusertib)...Our findings revealed distinct expression signatures associated with favorable responses to two ATR inhibitors when individually combined with TMZ, highlighting candidate markers that could guide treatment decisions. Additional validation in a larger study would establish the potential utility of these candidate genes..."

Biomarker • Oncology • MCM2 • MGMT

Everolimus and Sunitinib potentially work as therapeutic drugs for infantile hemangiomas. (PubMed, Pediatr Res) - "Developed a novel immortalized hemangioma-derived endothelial cell (iHemEC) model that replicates key IH features, overcoming limitations of primary cell models. Identified Sunitinib and Everolimus as promising therapeutic candidates with superior efficacy, supported by transcriptome and protein analyses. Revealed distinct drug mechanisms, with Everolimus targeting PI3K/AKT/mTOR and Sunitinib inducing chromosome instability and DNA damage."

IO biomarker • Journal • Oncology • BCL2 • HIF1A

Elimusertib, a Novel ATR Inhibitor, Induces Anti-Tumor Effects through Replication Catastrophe in Breast Cancers. (PubMed, Cancer Res Treat) - "Moreover, cells under high DNA replication stress were sensitive to elimusertib. Further studies and treatment strategies with elimusertib are warranted for cancers with a high replication rate."

Journal • Ataxia • Breast Cancer • Immunology • Movement Disorders • Oncology • Primary Immunodeficiency • Solid Tumor • ANXA5 • CASP7

ETCTN 10402: Testing the Addition of an Anti-cancer Drug, BAY 1895344, to Usual Chemotherapy for Advanced Stage Solid Tumors, With a Specific Focus on Patients With Small Cell Lung Cancer, Poorly Differentiated Neuroendocrine Cancer, and Pancreatic Cancer (clinicaltrials.gov) - P1 | N=28 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | N=96 ➔ 28 | Trial completion date: Feb 2025 ➔ Mar 2026

Enrollment change • Trial completion date • Endocrine Cancer • Hepatology • Lung Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Small Cell Lung Cancer • Solid Tumor

Targeting ATR and PKMYT1 to overcome carboplatin resistance in triple-negative breast cancer patient-derived models (ESMO-TAT 2025) - "Our results highlight the susceptibility of TNBC to targeted cell cycle modulators when used with DNA damage agents like carboplatin and this vulnerability could enhance treatment efficacy in TNBC."

Clinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CDK1 • FOXM1 • PKMYT1

Targeting Ataxia Telangiectasia-Mutated and Rad3-Related for Anaplastic Thyroid Cancer. (PubMed, Cancers (Basel)) - "These results reveal that BAY 1895344 has potential in treating ATC."

Journal • Ataxia • Endocrine Cancer • Immunology • Movement Disorders • Oncology • Primary Immunodeficiency • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • CASP3

Targeting ATR to overcome cisplatin resistance in hepatoblastoma (LCS 2025) - "Elimusertib also showed synergy with other HB chemotherapeutic agents, including carboplatin, irinotecan and/or vincristine and demonstrated ability to inhibit mTOR. This study highlights the crucial role of ATR in mediating cisplatin resistance and demonstrates the potent cytotoxic effects of the elimusertib/cisplatin combination in cisplatin- resistant HB models. These findings identified a promising new therapeutic option for treating chemoresistant HB."

Gastrointestinal Cancer • Hepatoblastoma • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Targeting Ataxia Telangiectasia-Mutated and Rad3-Related for Anaplastic Thyroid Cancer (Multidisciplinary Digital Publishing Institute) - "BAY 1895344 caused dose–response cytotoxicity in three ATC cell lines. BAY 1895344 induced S-phase and G2-phase arrest, activated caspase-3 activity and induced apoptosis in ATC cells. BAY 1895344 meaningfully retarded the tumor growth of an ATC xenograft model."

Preclinical • Thyroid Gland Anaplastic Carcinoma

Gemcitabine and ATR inhibitors synergize to kill PDAC cells by blocking DNA damage response. (PubMed, Mol Syst Biol) - "Here, we phenotypically screened 13 human pancreatic adenocarcinoma (PDAC) cell lines against GEM in combination with 146 clinical inhibitors and observed strong synergy for the ATR kinase inhibitor Elimusertib in most cell lines. Dose-dependent phosphoproteome profiling of four ATR inhibitors following DNA damage induction by GEM revealed a strong block of the DNA damage response pathway, including phosphorylated pS468 of CHEK1, as the underlying mechanism of drug synergy. The current work provides a strong rationale for why the combination of GEM and ATR inhibition may be useful for the treatment of PDAC patients and constitutes a rich phenotypic and molecular resource for further investigating effective drug combinations."

Journal • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CHEK1

Phase I trial of ATR inhibitor elimusertib with FOLFIRI in advanced or metastatic gastrointestinal malignancies (ETCTN 10406). (PubMed, Cancer Chemother Pharmacol) - P1 | "The combination of elimusertib with FOLFIRI was associated with intolerable toxicity. Combination of ATR kinases with chemotherapies that target DNA replication may be associated with significant myelotoxicity. Ongoing ATRi trials should monitor for t-AML."

Journal • P1 data • Acute Myelogenous Leukemia • Colorectal Cancer • Febrile Neutropenia • Gastrointestinal Cancer • Gastrointestinal Disorder • Hematological Disorders • Leukopenia • Mucositis • Neutropenia • Oncology • Solid Tumor

Enhancing T-DXd Efficacy in HER2-positive Breast Cancer Resistant to HER2 ADC by Non-biased Kinase-related Target Screening. (SABCS 2024) - "Background: Anti-HER2 antibody-drug conjugate (HER2-ADC) therapies, such as trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd), significantly prolong survival in patients with HER2-positive metastatic breast cancer (BC) compared to physician's choice of chemotherapy with trastuzumab (The EMILIA, TH3RESA, and DESTINY-Breast clinical trials)...Importantly, we further observed the synergy of elimusertib and T-DXd in parental HER2-positive BC cell lines, ensuring the observed effects are not limited to resistant cell lines only... Our findings indicate that resistance to HER2-ADC therapies is associated with increased DNA repair-related genes. By non-biased screening, this study provides robust evidence that targeting DNA repair pathways can significantly enhance the efficacy of T-DXd in HER2-ADC-resistant HER2-positive BC. The potential of combining ATR inhibitors with TDXd to overcome resistance and improve patient outcomes is a promising avenue that..."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ATM • CDK12 • HER-2 • PCNA • RAD21 • RAD52 • TOP2A

ATR Inhibitor Elimusertib Suppresses Drug Persister Clones in TP53-Mutated Acute Myeloid Leukemia Via CGAS-Sting-Mediated Cell Death (ASH 2024) - "Among these, the ataxia telangiectasia and Rad3-related protein (ATR) inhibitor elimusertib (BAY1895344) effectively inhibited TP53 mut AML DTPCs at low doses, similar to known inhibitors the CHK1 inhibitor (SRA737) and the Wee1 inhibitor (Adavosertib)...Furthermore, the triple combination treatment of cytarabine, idarubicin, and elimusertib effectively suppressed DTPC formation in TP53 mut AML cell lines...This consequently results in cGAS-STING-mediated cell death following irreparable DNA replication stress accompanied by p53 dysfunction. Our findings provide a basis for developing optimized treatment strategies for patients with TP53-mutant AML using the ATR inhibitor elimusertib."

Acute Myelogenous Leukemia • Ataxia • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Movement Disorders • Oncology • Primary Immunodeficiency • CDC25C • CDK1 • CDKN1A • CXCL10 • GNRP • IFI27 • IFIT1 • RSAD2 • SIGLEC1 • STAT1 • STING • TP53

Testing the Addition of an Anti-cancer Drug, BAY 1895344, With Radiation Therapy to the Usual Pembrolizumab Treatment for Recurrent Head and Neck Cancer (clinicaltrials.gov) - P1 | N=7 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | N=37 ➔ 7 | Trial completion date: Nov 2024 ➔ Dec 2025

Enrollment change • Trial completion date • Tumor mutational burden • Head and Neck Cancer • Hypopharyngeal Cancer • Laryngeal Cancer • Oncology • Oral Cancer • Oropharyngeal Cancer • Otorhinolaryngology • Salivary Gland Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • Thyroid Gland Carcinoma • CD4 • CD8 • TMB