Tuvusertib Combined With Niraparib or Lartesertib in Participants With Epithelial Ovarian Cancer (DDRiver EOC 302)

June 2, 2026 updated by: EMD Serono Research & Development Institute, Inc.

An Open-label, Multicenter, Randomized Phase 2 Study of the ATR Inhibitor Tuvusertib in Combination With the PARP Inhibitor Niraparib or the ATM Inhibitor Lartesertib in Participants With BRCA Mutant and/or Homologous Recombination deficiency (HRD)-Positive Epithelial Ovarian Cancer That Progressed on Prior PARP Inhibitor Therapy (DDRiver EOC 302)

The purpose of this study is to measure the effect and safety of treatment with tuvusertib combined with either niraparib or lartesertib in participants with epithelial ovarian cancer and to assess any differences between tuvusertib monotherapy and combination therapy. The participants will previously have progressed while treated with a poly ADP ribose polymerase (PARP) inhibitor. The primary objectives of this study are to assess the effect of the treatment in terms of overall response, i.e. whether the tumor disappears, shrinks, remains unchanged, or gets worse and safety in terms of adverse events.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

63

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Camperdown, Australia
        • Chris O'Brien Lifehouse
      • Kogarah, Australia
        • St George Private Hospital
      • Liverpool, Australia
        • Liverpool Hospital - PARENT
  • Belgium
      • Brussels, Belgium
        • Cliniques Universitaires Saint-Luc - STL
      • Leuven, Belgium
        • UZ Leuven
  • Denmark
      • Aalborg, Denmark
        • Ålborg Universitets Hospital - PARENT
      • Copenhagen, Denmark
        • Rigshospitalet
      • Odense, Denmark
        • Sjaellands Universitetshospital - other
  • France
      • Angers, France
        • ICO - Site Paul Papin - service d'oncologie medicale
      • Caen, France
        • Centre Francois Baclesse - Service d'Oncologie Medicale
      • Lille, France
        • Centre Oscar Lambret - service de cancerologie gynecologique
      • Lyon, France
        • Centre Leon Berard - Service d'Oncologie Medicale
      • Paris, France
        • Groupe Hospitalier Diaconesses - Hôpital De La Croix Saint Simon - service d'oncologie medicale
      • Paris, France
        • Hôpital Cochin - Hematologie et Oncologie Médicale
      • Paris, France
        • Hopital Tenon - service d'oncologie medicale
      • Paris, France
        • Hôpital Européen Georges Pompidou - Hématologie Oncologie
      • Paris, France
        • Hôpital Saint Joseph - Paris - Service d'Oncologie-Cancerologie
      • Pierre-Bénite, France
        • Centre Hospitalier Lyon Sud - service d'oncologie medicale
      • Strasbourg, France
        • Institut de Cancérologie de Strasbourg Europe - ICANS - Service d'oncologie médicale
      • Strasbourg, France
        • Centre de Radiotherapie Clinique Sainte Anne - 300207251
      • Villejuif, France
        • Institut Gustave Roussy - Oncologie Médicale
  • Germany
      • Berlin, Germany
        • Charité - Campus Virchow-Klinikum - Klinik fuer Gynaekologie
      • Bonn, Germany
        • Universitaetsklinikum Bonn AoeR - Frauenklinik
      • Dresden, Germany
        • Universitaetsklinikum Carl Gustav Carus TU Dresden - Klinik u. Poliklinik f. Frauenheilkunde
      • Essen, Germany
        • Kliniken Essen-Mitte - Gynaekologie und Gynaekologische Onkologie
      • Leipzig, Germany
        • Universitaetsklinikum Leipzig AoeR - Klinik und Poliklinik fuer Frauenheilkunde
      • Münster, Germany
        • Universitaetsklinikum Muenster - Parent
      • Münster, Germany
        • Universitätsklinikum Münster - Gynecology
      • Regensburg, Germany
        • Caritas-Krankenhaus St. Josef - Klinik fuer Chirurgie
      • Tübingen, Germany
        • Universitaetsklinikum Tuebingen - Parent
  • Israel
      • Haifa, Israel
        • Rambam Medical Center
      • Haifa, Israel
        • The Lady Davis Carmel Medical Center
      • Jerusalem, Israel
        • Shaare Zedek
      • Jerusalem, Israel
        • Hadassah University Hospital - Ein Kerem
      • Ramat Gan, Israel
        • Chaim Sheba Medical Center
  • Italy
      • Bologna, Italy
        • Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS - Oncologia Medica
      • Bologna, Italy
        • IRCCS Azienda Ospedaliero Universitaria di Bologna Policlinico di Sant Orsola - SSD Oncologia Medica Zamagni
      • Catania, Italy
        • Osp Cannizzaro Catania
      • Catanzaro, Italy
        • Azienda Ospedaliero-Universitaria Renato Dulbecco - Centro Oncologico
      • Milan, Italy
        • IEO Istituto Europeo di Oncologia - Unità Ginecologia Oncologica Medica
      • Milan, Italy
        • Istituto Clinico Humanitas - U.O. di Oncologia Medica ed Ematologia
      • Naples, Italy
        • Istituto Nazionale Tumori Fondazione G. Pascale - Gynecology
      • Padova, Italy
        • IOV - Istituto Oncologico Veneto IRCCS - Radiologia Oncologica
      • Roma, Italy
        • Istituto Nazionale Tumori Regina Elena IRCCS - UOC Oncologia Medica A
      • Rome, Italy
        • Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Ostetricia e ginecologia
  • Netherlands
      • Eindhoven, Netherlands
        • Catharina Ziekenhuis Eindhoven - Parent
  • Poland
      • Bydgoszcz, Poland
        • Centrum Onkologii im. Prof. F. Lukaszczyka w Bydgoszczy - Dept of Chemotherapy
      • Gdynia, Poland
        • Szpitale Pomorskie spó
      • Krakow, Poland
        • Jagiellonskie Centrum Innowacji Sp. z o.o. - Centrum Bada
      • Lodz, Poland
        • Instytut MSF Sp.z.o.o
      • Otwock, Poland
        • Europejskie Centrum Zdrowia - Oddzial Onkologii
      • Torun, Poland
        • MICS Centrum Medyczne Torun - Medicovernn
  • Spain
      • Badalona, Spain
        • ICO Badalona - Hospital Universitari Germans Trias i Pujol - Servicio de Oncologia Medica
      • Barcelona, Spain
        • Hospital Universitari Vall d'Hebron - Oncology Dept.
      • Barcelona, Spain
        • Hospital Clinic de Barcelona - Servicio de Oncologia
      • Girona, Spain
        • ICO Girona - Hospital Universitari de Girona Dr Josep Trueta - Servicio de Oncologia Medica
      • Madrid, Spain
        • Hospital Universitario 12 de Octubre - Servicio de Oncologia
      • Madrid, Spain
        • Hospital Universitario Ramon y Cajal - Servicio de Oncologia
      • Madrid, Spain
        • Clinica Universidad de Navarra (MAD) - Oncology Service
      • Málaga, Spain
        • Hospital Regional Universitario de Malaga - Oncology Dept
  • Switzerland
      • Bellinzona, Switzerland
        • Istituto Oncologico della Svizzera Italiana (IOSI)- Ente Ospedaliero Cantonale (EOC) - Ospedale S.Giovann
      • Frauenfeld, Switzerland
        • Kantonsspital Frauenfeld - 150509250
      • Liestal, Switzerland
        • Kantonsspital Baselland - standort Liestal - Klinik fuer Onkologie
      • Sankt Gallen, Switzerland
        • Kantonsspital St. Gallen - Klinik fuer Med. Onkologie/Haematologie
      • Zurich, Switzerland
        • Universitaetsspital Zuerich - Klinik fuer Gynaekologie
  • United Kingdom
      • Cambridge, United Kingdom
        • Addenbrooke's Hospital - Dept of Oncology
      • Glasgow, United Kingdom
        • Beatson West of Scotland Cancer Centre - Dept of Medical Oncology
      • Guildford, United Kingdom
        • Royal Surrey County Hospital - Dept of Oncology
      • Leeds, United Kingdom
        • St James's University Hospital - Dept of Oncology
      • London, United Kingdom
        • University College London Hospitals - NIHR/Wellcome Trust
      • London, United Kingdom
        • Royal Marsden Hospital-London - Dept of Haematology/Oncology Research
      • London, United Kingdom
        • Guy's Hospital - Dept of Medical Oncology
      • Manchester, United Kingdom
        • The Christie Hospital - Dept of Oncology
      • Northwood, United Kingdom
        • Mount Vernon Hospital - Dept of Oncology
      • Sutton, United Kingdom
        • Royal Marsden Hospital-Sutton - Dept of Oncology (Surrey)
  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas for Medical Sciences
    • California
      • San Francisco, California, United States, 94158
        • University of California San Francisco - UCSF Medical Center
    • Georgia
      • Columbus, Georgia, United States, 31904
        • Centricity Research Cancer Center - DBA CRRI John B. Amos Cancer Center Research
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Comprehensive Cancer Center at Silver Cross - Carolyn J. Czerkies Pavilion
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Rogel Cancer Center
    • New York
      • New York, New York, United States, 10021
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10029
        • Icahn School of Medicine at Mount Sinai PRIME - Mount Sinai - PRIME
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Virginia Cancer Specialists, PC
      • Fairfax, Virginia, United States, 22031
        • NEXT Oncology - Virginia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically or cytologically confirmed high grade serous or high grade endometrioid ovarian, primary peritoneal, and/or fallopian tube cancer that is recurrent.
  • Participants whose tumor carries germline or somatic deleterious or suspected deleterious mutations in the genes BRCA1 (Breast Cancer gene 1) and BRCA2 (Breast Cancer gene 2), and/or tumors with positive HRD status. The presence of any of these mutations and/or the homologous recombination deficiency (HRD) status will be determined according to routinely used local standard of care tests. Results must be available before screening.
  • Radiologically confirmed/documented disease progression while on Poly (ADP-ribose) polymerase (PARP) inhibitors therapy in either first or second-line maintenance setting (only 1 line of PARPi maintenance is allowed with or without bevacizumab). Note: Documentation of disease progression must be within 28 days of last PARPi dose taken. Surgical salvage intervention and/or focal ablative therapies are allowed, (further disease progression after these interventions must be documented), AND Clinically benefited from PARPi maintenance prior to documented progression, as defined by at least 6 months of treatment duration with no progressive disease observed, AND either, Progression on first-line maintenance PARPi: Participants are allowed maximum 1 additional line of platinum-based chemotherapy before study entry. (note: treatment-free interval on platinum rechallenge must be >6 months, with documented disease progression prior to study entry).

OR Progression on second-line maintenance PARPi: Participants are not allowed any additional systemic anticancer treatments before study entry (that is PARPi is the last treatment before study entry)

  • Intolerant to standard of care treatment options or refused standard of care treatment or the participant's treating physician considers that the lack of standard of care treatment is not detrimental for the participant.
  • Measurable disease per RECIST v1.1, as assessed by Investigator.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and a life expectancy of at least 6 months.
  • Other Protocol defined inclusion criteria could apply.

Exclusion Criteria:

  • Primary platinum-refractory disease defined as disease progression during primary platinum-based chemotherapy or platinum-resistant disease defined as disease progression within 6 months of the platinum administration in either the first or second-line setting.
  • History of additional malignancy within 3 years before the date of enrollment.
  • Known brain metastases, unless clinically stable, that is without evidence of progression by imaging for at least 4 weeks prior to the first dose of study intervention, no evidence of new brain metastases, and on a stable or decreasing dose of ≤ 10 mg of prednisone (or equivalent) or without corticosteroids for at least 14 days prior to study intervention administration.
  • Active and/or uncontrolled infection.
  • History of known hypersensitivity to the active substances or to any excipients (e.g. polysorbate 80) of the study interventions.
  • Organ transplantation, including allogenic stem cell transplant.
  • Patients with history of drug-induced severe cutaneous adverse reaction (SCAR; including but not limited to Stevens-Johnson syndrome/toxic epidermal necrolysis [SJS/TEN], or drug reaction with eosinophilia and systemic symptoms [DRESS]), or dose-limiting immune-mediated reactions related to skin.
  • Other Protocol defined exclusion criteria could apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part A, Arm 1: Tuvusertib with Niraparib
In Part A, participants will be randomized to one of 2 arms to receive tuvusertib in combination with either niraparib or lartesertib.
Drug: Tuvusertib (M1774)
Tuvusertib will be administered orally.
Other Names:
  • M1774, VXc-400, VRT-1363004, substance code MSC2584415A
Drug: Niraparib
Niraparib will be administered orally. If selected from Part A, Niraparib will be administered orally in combination with Tuvusertib.
Other Names:
  • GSK3985771, MK-4827
Experimental: Part A, Arm 2: Tuvusertib with Lartesertib
In Part A, participants will be randomized to one of 2 arms to receive tuvusertib in combination with either niraparib or lartesertib.
Drug: Tuvusertib (M1774)
Tuvusertib will be administered orally.
Other Names:
  • M1774, VXc-400, VRT-1363004, substance code MSC2584415A
Drug: Lartesertib (M4076)
Lartesertib will be administered orally. If selected from Part A, Lartesertib will be administered orally in combination with Tuvusertib
Other Names:
  • M4076, substance code MSC2585823A
Experimental: Part B (dose optimization), dosing regimen 1 :Tuvusertib+Niraparib or Tuvusertib +Lartesertib
In Part B, the most favorable combination treatment from Part A will be further explored at 2 different dosing regimens and compared to tuvusertib monotherapy.
Drug: Tuvusertib (M1774)
Tuvusertib will be administered orally.
Other Names:
  • M1774, VXc-400, VRT-1363004, substance code MSC2584415A
Drug: Niraparib
Niraparib will be administered orally. If selected from Part A, Niraparib will be administered orally in combination with Tuvusertib.
Other Names:
  • GSK3985771, MK-4827
Drug: Lartesertib (M4076)
Lartesertib will be administered orally. If selected from Part A, Lartesertib will be administered orally in combination with Tuvusertib
Other Names:
  • M4076, substance code MSC2585823A
Experimental: Part B (dose optimization), dosing regimen 2: Tuvusertib + Niraparib or Tuvusertib + Lartesertib
In Part B, the most favorable combination treatment from Part A will be further explored at 2 different dosing regimens and compared to tuvusertib monotherapy.
Drug: Tuvusertib (M1774)
Tuvusertib will be administered orally.
Other Names:
  • M1774, VXc-400, VRT-1363004, substance code MSC2584415A
Drug: Niraparib
Niraparib will be administered orally. If selected from Part A, Niraparib will be administered orally in combination with Tuvusertib.
Other Names:
  • GSK3985771, MK-4827
Drug: Lartesertib (M4076)
Lartesertib will be administered orally. If selected from Part A, Lartesertib will be administered orally in combination with Tuvusertib
Other Names:
  • M4076, substance code MSC2585823A
Experimental: Part B: Tuvusertib Monotherapy
In Part B, the most favorable combination treatment from Part A will be further explored at 2 different dosing regimens and compared to tuvusertib monotherapy.
Drug: Tuvusertib (M1774)
Tuvusertib will be administered orally.
Other Names:
  • M1774, VXc-400, VRT-1363004, substance code MSC2584415A

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Part A and Part B: Confirmed Objective Response (OR) According to RECIST v1.1 as Assessed by Investigator
Time Frame: Time from randomization to final assessment or until progressive disease, death, discontinuation criteria, approximately up to 3.5 years
Time from randomization to final assessment or until progressive disease, death, discontinuation criteria, approximately up to 3.5 years
Part A and Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs and Related TEAEs
Time Frame: Time from randomization to final assessment at end of safety follow-up visit, approximately up to 3.5 years
Time from randomization to final assessment at end of safety follow-up visit, approximately up to 3.5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part A and Part B: Duration of Response (DoR) According to RECIST 1.1 as Assessed by the Investigator
Time Frame: Time from randomization to final assessment or until progressive disease, death, discontinuation criteria, approximately up to 3.5 years
Time from randomization to final assessment or until progressive disease, death, discontinuation criteria, approximately up to 3.5 years
Part A and Part B: Progression Free Survival (PFS) According to RECIST 1.1 as Assessed by the Investigator
Time Frame: Time from randomization to final assessment or until progressive disease, death, discontinuation criteria, approximately up to 3.5 years
Time from randomization to final assessment or until progressive disease, death, discontinuation criteria, approximately up to 3.5 years
Part B: Overall Survival
Time Frame: Time from date of randomization to death, approximately 3.5 years
OS is defined as the time from randomization to death due to any cause.
Time from date of randomization to death, approximately 3.5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

EMD Serono Research & Development Institute, Inc.

Collaborators

Merck KGaA, Darmstadt, Germany

Investigators

  • Study Director: Medical Responsible, EMD Serono Research & Development Institute, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 30, 2024

Primary Completion (Estimated)

June 14, 2026

Study Completion (Estimated)

June 14, 2026

Study Registration Dates

First Submitted

May 22, 2024

First Submitted That Met QC Criteria

May 22, 2024

First Posted (Actual)

May 29, 2024

Study Record Updates

Last Update Posted (Actual)

June 3, 2026

Last Update Submitted That Met QC Criteria

June 2, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MS201924_0002
  • 2024-511202-23-00 (Other Identifier: EU trial number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21

IPD Sharing Time Frame

Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union

IPD Sharing Access Criteria

Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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