tuvusertib (M1774) / EMD Serono - LARVOL DELTA

Tuvusertib Combined With Niraparib or Lartesertib in Participants With Epithelial Ovarian Cancer (DDRiver EOC 302) (clinicaltrials.gov) - P2 | N=63 | Completed | Sponsor: EMD Serono Research & Development Institute, Inc. | Active, not recruiting ➔ Completed

Trial completion • Breast Cancer • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA1 • BRCA2 • HRD

Tuvusertib in Recurrent IDH and ATRX mutant Astrocytoma: Design of the Phase 2 GEINO-2401 / TUVASTRAT Study (ESMO 2026) - No abstract available

P2 data • Astrocytoma • Brain Cancer • Oncology • Solid Tumor • ATRX

ATR inhibitors synergise with mitomycin C to enhance cytotoxicity in patient-derived non-muscle invasive bladder cancer organoids. (PubMed, Br J Cancer) - "This study demonstrates synergy between ATR inhibitors and chemotherapy in NMIBC PDOs. Combining intravesical chemotherapy instillations with DNA damage response inhibitors should be further evaluated as a promising strategy to reduce recurrence rates for NMIBC."

Journal • Ataxia • Bladder Cancer • Genito-urinary Cancer • Immunology • Movement Disorders • Oncology • Primary Immunodeficiency • Solid Tumor

MATRiX: A randomized phase II trial of tuvusertib (ATR inhibitor) with or without avelumab in advanced anti-PD(L)-1 refractory Merkel cell carcinoma. (ASCO 2026) - P2 | "Tuvusertib with avelumab demonstrated antitumor activity in anti-PD-(L)1-refractory MCC, inducing durable clinical benefit in ICI-resistant metastatic pts with limited salvage options. No signal of anticancer efficacy was observed with ATRi monotherapy. These findings warrant further investigation of ATRi in combination with immunotherapy in ICI-refractory MCC."

Clinical • IO biomarker • Late-breaking abstract • Metastases • P2 data • Ataxia • Immunology • Infectious Disease • Merkel Cell Carcinoma • Movement Disorders • Non-melanoma Skin Cancer • Oncology • Primary Immunodeficiency • Skin Cancer • Solid Tumor

Tuvusertib (M1774) in Combination With Cemiplimab in Participants With Non-Squamous NSCLC (DDRiver NSCLC 322) (clinicaltrials.gov) - P1/2 | N=61 | Completed | Sponsor: EMD Serono Research & Development Institute, Inc. | Active, not recruiting ➔ Completed

Trial completion • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

MS201924_0020: Study of Tuvusertib (M1774) in Combination With DNA Damage Response Inhibitor or Immune Checkpoint Inhibitor (DDRiver Solid Tumors 320) (clinicaltrials.gov) - P1 | N=120 | Completed | Sponsor: EMD Serono Research & Development Institute, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Jan 2027 ➔ Jul 2026 | Trial primary completion date: Jan 2027 ➔ Jul 2026

Checkpoint inhibition • dMMR • IO biomarker • Trial completion • Trial completion date • Trial primary completion date • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer • ARID1A • ATM

Testing the Combination of Two Anti-cancer Drugs, Peposertib (M3814) and Tuvusertib (M1774) for Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=66 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Aug 2026 ➔ Aug 2027 | Trial primary completion date: Aug 2026 ➔ Aug 2027

Trial completion date • Trial primary completion date • Oncology • Solid Tumor • ARID1A • ARID1B • ARID2 • ATM • ATRX • CCNE1 • FBXW7 • MYC • PBRM1 • SMARCA2 • SMARCB1 • SS18

DDRiver Solid Tumours 301: Tuvusertib (M1774) in Participants With Metastatic or Locally Advanced Unresectable Solid Tumors (DDRiver Solid Tumors 301) (clinicaltrials.gov) - P1 | N=161 | Active, not recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | Trial completion date: Jul 2026 ➔ Nov 2026 | Trial primary completion date: Jul 2026 ➔ Nov 2026

First-in-human • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • ARID1A • ATRX

Duocarmycin-Bearing Antibody-Mimetic Drug Conjugate Combined With an ATR Inhibitor Results in Complete Tumor Regression in a KPL-4 Xenograft Model. (PubMed, Cancer Med) - "Synergistic interactions with Duo-HER2 were further confirmed in vitro using three clinically relevant ATR inhibitors-tuvusertib, ceralasertib, and berzosertib. Together, these findings indicate that Duo-HER2 combined with ATR inhibitors synergistically suppresses tumor growth in HER2-positive breast cancer models. Further studies employing optimized formulations, expanded in vivo cohorts, and additional tumor models will be required to fully define the therapeutic potential of this strategy and its relevance for overcoming ADC resistance."

Journal • Preclinical • Ataxia • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Immunology • Movement Disorders • Oncology • Primary Immunodeficiency • Solid Tumor • HER-2

M9466 Alone or in Combination in Advanced Solid Tumors (DDriver 501) (clinicaltrials.gov) - P1 | N=60 | Active, not recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | N=141 ➔ 60

Enrollment change • Oncology • Prostate Cancer • Solid Tumor

Combination Treatment Targeting Cancer Stem Cell Subpopulation Reverting Chemoresistance in Germ Cells Tumors (EACR 2026) - "Material and A broad panel of parental and cisplatin-resistant (CisR) isogenic GCT cell lines was analyzed for TACSTD2 (TROP-2) expression by RT-qPCR, and sensitivity to sacituzumab govitecan was assessed at day 3 using an endpoint luminescence assay. To explore strategies for overcoming chemoresistance, combination treatments were performed with a panel of targeted pathway inhibitors affecting cell cycle, DNA damage response, transcriptional regulation, and oncogenic signaling (Tuvusertib [CDK7 inhibitor], Ceralasertib [ATR inhibitor], Adavosertib [WEE1 inhibitor], Simvastatin, Copanlisib, ABVV-744, Cyclosporin A, Dasatinib, Crizotinib, Tozasertib, Alpelisib, Selumetinib) to evaluate potential synergistic effects.Result and We focused on the transmembrane glycoprotein TROP-2 (trophoblast cell surface antigen 2), involved in proliferation, migration, and invasiveness, which is overexpressed in multiple solid tumors... Our findings support further investigation of..."

Cancer stem • Clinical • Germ Cell Tumors • Oncology • Solid Tumor • Testicular Cancer • TACSTD2

Tuvusertib (M1774) in Combination With Cemiplimab in Participants With Non-Squamous NSCLC (DDRiver NSCLC 322) (clinicaltrials.gov) - P1/2 | N=180 | Recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | Phase classification: P1b/2a ➔ P1/2

Combination therapy • Phase classification • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Tuvusertib (M1774) in Combination With Cemiplimab in Participants With Non-Squamous NSCLC (DDRiver NSCLC 322) (clinicaltrials.gov) - P1/2 | N=61 | Active, not recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | Trial completion date: Mar 2026 ➔ Sep 2026 | Trial primary completion date: Mar 2026 ➔ Sep 2026

Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

NRG-GY031: Testing Different Amounts of the Combination of Drugs M1774 and ZEN-3694 for the Treatment of Recurrent Ovarian and Endometrial Cancer (clinicaltrials.gov) - P1 | N=65 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Apr 2026 ➔ Jun 2027 | Trial primary completion date: Apr 2026 ➔ Jun 2027

dMMR • MSI-H • Platinum resistant • Trial completion date • Trial primary completion date • Endometrial Adenocarcinoma • Endometrial Cancer • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • ARID1A • MSI

Tuvusertib Combined With Niraparib or Lartesertib in Participants With Epithelial Ovarian Cancer (DDRiver EOC 302) (clinicaltrials.gov) - P2 | N=63 | Active, not recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | Trial primary completion date: Sep 2025 ➔ Jun 2026

Trial primary completion date • Breast Cancer • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA1 • BRCA2 • HRD

Study of Tuvusertib (M1774) in Combination With DNA Damage Response Inhibitor or Immune Checkpoint Inhibitor (DDRiver Solid Tumors 320) (clinicaltrials.gov) - P1 | N=120 | Active, not recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | Trial completion date: Apr 2026 ➔ Jan 2027 | Trial primary completion date: Apr 2026 ➔ Jan 2027

Checkpoint inhibition • IO biomarker • Trial completion date • Trial primary completion date • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer • ARID1A • ATM

DDRiver Solid Tumours 301: Tuvusertib (M1774) in Participants With Metastatic or Locally Advanced Unresectable Solid Tumors (DDRiver Solid Tumors 301) (clinicaltrials.gov) - P1 | N=161 | Active, not recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | Trial completion date: Jan 2027 ➔ Jul 2026 | Trial primary completion date: Jan 2027 ➔ Jul 2026

First-in-human • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • ARID1A • ATRX

Structure Elucidation and Initial Characterization of a N-glucuronide Metabolite (M1) of Tuvusertib. (PubMed, Eur J Drug Metab Pharmacokinet) - "The tuvusertib metabolite M1 was identified as an N-glucuronide demonstrating no direct liabilities associated with drug-drug interactions (DDI) or safety implications. Furthermore, M1 can be used in bioanalyses as retention time marker or reference material in further clinical evaluations."

Journal

Testing the Effect of M1774 on Hard-to-Treat Refractory SPOP-mutant Prostate Cancer (clinicaltrials.gov) - P2 | N=20 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jun 2026 ➔ Jan 2027 | Trial primary completion date: Jun 2026 ➔ Jan 2027

Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • SPOP

Tuvusertib (M1774) Human Mass Balance and Absolute Bioavailability Study (DDRIVER Solid Tumors 303) (clinicaltrials.gov) - P1 | N=12 | Completed | Sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany | Active, not recruiting ➔ Completed

Trial completion • Oncology • Solid Tumor

Targeting cyclin K-CDK12 synergizes with ATR inhibition by limiting RPA chromatin loading in triple-negative breast cancer (AACR 2026) - "This impaired ATR activation is further exacerbated when combined with tuvusertib (ATRi), leading to marked DNA damage specifically in replicating cells...Collectively, our work identifies cyclin K-CDK12 as a critical regulator of RPA dynamics and uncovers ATR dependency driven by cyclin K-CDK12 depletion. These insights extend the rationale for cyclin K-CDK12 targeted therapy beyond HR repair-focused applications, supporting its use in RS-high tumors including TNBC, as monotherapy or in combination with ATR inhibition."

Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CDK12 • ER • MYC • PRPF19 • TOPBP1

Improved natural killer cell targeting of prostate carcinoma with ATR inhibitor tuvusertib in combination with IL-15 receptor superagonist N-803 (IMMUNOLOGY 2026) - "Tuvusertib rendered PCa cells more susceptible to NK-mediated lysis and PD-L1-targeting by avelumab-mediated antibody-dependent cellular cytotoxicity (ADCC) and PD-L1 t-haNK cells. Immune-mediated targeting of prostate carcinoma is improved by tuvusertib ATRi which can be combined with avelumab and/or N-803."

Combination therapy • IO biomarker • Ataxia • Genito-urinary Cancer • Immunology • Movement Disorders • Oncology • Primary Immunodeficiency • Prostate Cancer • Solid Tumor • IL15 • TNFRSF10B

In vitro evaluation of myelosuppressive effects of ATRi tuvusertib and ATMi lartesertib (M4076), alone and in combination (AACR 2024) - "The phenotypic and functional changes induced by tuvusertib and lartesertib on in vitro cultures of erythroid, myeloid, and megakaryocytic cells are consistent with clinical observations in monotherapy studies, suggesting these models may be used to better understand and predict the hematological effects of monotherapies and combinations in the clinic. In vitro washout experiments may help support the concept of intermittent clinical regimens and warrant further investigation.1. Martorana, et al."

Preclinical • Oncology • CD33 • CD34 • GYPA • ITGA2B • TFRC

Phase Ib trial of ATR inhibitor (ATRi) tuvusertib + ATM inhibitor (ATMi) lartesertib (M4076) in patients (pts) with advanced solid tumors (AACR 2024) - P1 | "Multiple tolerated combination doses were identified. Tuvusertib 180 mg QD + lartesertib 150 mg QD 2 w on/2 w off was selected for investigation in expansion cohorts in pts with prostate and endometrial cancer."

Clinical • Metastases • P1 data • Endometrial Cancer • Genito-urinary Cancer • Melanoma • Oncology • Prostate Cancer • Solid Tumor • ATM • PTPRC

Combined inhibition of ATR and ATM with tuvusertib and lartesertib (M4076) impacts the tumor microenvironment (AACR 2024) - "Turchick A, Zimmermann A, et al. Mol Cancer Ther 2023; 22(7):859-872."

Biomarker • IO biomarker • Tumor microenvironment • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD8 • PD-L1