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

NCT ID: NCT06433219

Last Updated: 2025-09-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

63 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-10-30

Study Completion Date

2028-01-25

Brief Summary

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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.

Detailed Description

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Conditions

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Ovarian Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Tuvusertib (M1774)

Intervention Type DRUG

Tuvusertib will be administered orally.

Niraparib

Intervention Type DRUG

Niraparib will be administered orally. If selected from Part A, Niraparib will be administered orally in combination with Tuvusertib.

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.

Group Type EXPERIMENTAL

Tuvusertib (M1774)

Intervention Type DRUG

Tuvusertib will be administered orally.

Lartesertib (M4076)

Intervention Type DRUG

Lartesertib will be administered orally. If selected from Part A, Lartesertib will be administered orally in combination with Tuvusertib

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.

Group Type EXPERIMENTAL

Tuvusertib (M1774)

Intervention Type DRUG

Tuvusertib will be administered orally.

Niraparib

Intervention Type DRUG

Niraparib will be administered orally. If selected from Part A, Niraparib will be administered orally in combination with Tuvusertib.

Lartesertib (M4076)

Intervention Type DRUG

Lartesertib will be administered orally. If selected from Part A, Lartesertib will be administered orally in combination with Tuvusertib

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.

Group Type EXPERIMENTAL

Tuvusertib (M1774)

Intervention Type DRUG

Tuvusertib will be administered orally.

Niraparib

Intervention Type DRUG

Niraparib will be administered orally. If selected from Part A, Niraparib will be administered orally in combination with Tuvusertib.

Lartesertib (M4076)

Intervention Type DRUG

Lartesertib will be administered orally. If selected from Part A, Lartesertib will be administered orally in combination with Tuvusertib

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.

Group Type EXPERIMENTAL

Tuvusertib (M1774)

Intervention Type DRUG

Tuvusertib will be administered orally.

Interventions

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Tuvusertib (M1774)

Tuvusertib will be administered orally.

Intervention Type DRUG

Niraparib

Niraparib will be administered orally. If selected from Part A, Niraparib will be administered orally in combination with Tuvusertib.

Intervention Type DRUG

Lartesertib (M4076)

Lartesertib will be administered orally. If selected from Part A, Lartesertib will be administered orally in combination with Tuvusertib

Intervention Type DRUG

Other Intervention Names

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M1774, VXc-400, VRT-1363004, substance code MSC2584415A GSK3985771, MK-4827 M4076, substance code MSC2585823A

Eligibility Criteria

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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.

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.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role collaborator

EMD Serono Research & Development Institute, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Responsible

Role: STUDY_DIRECTOR

EMD Serono Research & Development Institute, Inc.

Locations

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University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

University of California San Francisco - UCSF Medical Center

San Francisco, California, United States

Site Status

Centricity Research Cancer Center - DBA CRRI John B. Amos Cancer Center Research

Columbus, Georgia, United States

Site Status

University of Chicago Comprehensive Cancer Center at Silver Cross - Carolyn J. Czerkies Pavilion

Chicago, Illinois, United States

Site Status

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Icahn School of Medicine at Mount Sinai PRIME - Mount Sinai - PRIME

New York, New York, United States

Site Status

Next Oncology - Virginia

Fairfax, Virginia, United States

Site Status

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Site Status

Chris O'Brien Lifehouse

Camperdown, , Australia

Site Status

St George Private Hospital

Kogarah, , Australia

Site Status

Liverpool Hospital - PARENT

Liverpool, , Australia

Site Status

Cliniques Universitaires Saint-Luc - STL

Brussels, , Belgium

Site Status

UZ Leuven

Leuven, , Belgium

Site Status

Ålborg Universitets Hospital - PARENT

Aalborg, , Denmark

Site Status

Rigshospitalet

Copenhagen, , Denmark

Site Status

Sjaellands Universitetshospital - other

Odense, , Denmark

Site Status

ICO - Site Paul Papin - service d'oncologie medicale

Angers, , France

Site Status

Centre Francois Baclesse - Service d'Oncologie Medicale

Caen, , France

Site Status

Centre Oscar Lambret - service de cancerologie gynecologique

Lille, , France

Site Status

Centre Leon Berard - Service d'Oncologie Medicale

Lyon, , France

Site Status

Groupe Hospitalier Diaconesses - Hôpital De La Croix Saint Simon - service d'oncologie medicale

Paris, , France

Site Status

Hopital Tenon - service d'oncologie medicale

Paris, , France

Site Status

Hôpital Cochin - Hematologie et Oncologie Médicale

Paris, , France

Site Status

Hôpital Européen Georges Pompidou - Hématologie Oncologie

Paris, , France

Site Status

Hôpital Saint Joseph - Paris - Service d'Oncologie-Cancerologie

Paris, , France

Site Status

Centre Hospitalier Lyon Sud - service d'oncologie medicale

Pierre-Bénite, , France

Site Status

Centre de Radiotherapie Clinique Sainte Anne - 300207251

Strasbourg, , France

Site Status

Institut de Cancérologie de Strasbourg Europe - ICANS - Service d'oncologie médicale

Strasbourg, , France

Site Status

Institut Gustave Roussy - Oncologie Médicale

Villejuif, , France

Site Status

Charité - Campus Virchow-Klinikum - Klinik fuer Gynaekologie

Berlin, , Germany

Site Status

Universitaetsklinikum Bonn AoeR - Frauenklinik

Bonn, , Germany

Site Status

Universitaetsklinikum Carl Gustav Carus TU Dresden - Klinik u. Poliklinik f. Frauenheilkunde

Dresden, , Germany

Site Status

Kliniken Essen-Mitte - Gynaekologie und Gynaekologische Onkologie

Essen, , Germany

Site Status

Universitaetsklinikum Leipzig AoeR - Klinik und Poliklinik fuer Frauenheilkunde

Leipzig, , Germany

Site Status

Universitaetsklinikum Muenster - Parent

Münster, , Germany

Site Status

Universitätsklinikum Münster - Gynecology

Münster, , Germany

Site Status

Caritas-Krankenhaus St. Josef - Klinik fuer Chirurgie

Regensburg, , Germany

Site Status

Universitaetsklinikum Tuebingen - Parent

Tübingen, , Germany

Site Status

Rambam Medical Center

Haifa, , Israel

Site Status

The Lady Davis Carmel Medical Center

Haifa, , Israel

Site Status

Hadassah University Hospital - Ein Kerem

Jerusalem, , Israel

Site Status

Shaare Zedek

Jerusalem, , Israel

Site Status

Chaim Sheba Medical Center

Ramat Gan, , Israel

Site Status

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS - Oncologia Medica

Bologna, , Italy

Site Status

IRCCS Azienda Ospedaliero Universitaria di Bologna Policlinico di Sant Orsola - SSD Oncologia Medica Zamagni

Bologna, , Italy

Site Status

Osp Cannizzaro Catania

Catania, , Italy

Site Status

Azienda Ospedaliero-Universitaria Renato Dulbecco - Centro Oncologico

Catanzaro, , Italy

Site Status

IEO Istituto Europeo di Oncologia - Unità Ginecologia Oncologica Medica

Milan, , Italy

Site Status

Istituto Clinico Humanitas - U.O. di Oncologia Medica ed Ematologia

Milan, , Italy

Site Status

Istituto Nazionale Tumori Fondazione G. Pascale - Gynecology

Napoli, , Italy

Site Status

IOV - Istituto Oncologico Veneto IRCCS - Radiologia Oncologica

Padua, , Italy

Site Status

Istituto Nazionale Tumori Regina Elena IRCCS - UOC Oncologia Medica A

Roma, , Italy

Site Status

Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Ostetricia e ginecologia

Rome, , Italy

Site Status

Catharina Ziekenhuis Eindhoven - Parent

Eindhoven, , Netherlands

Site Status

Centrum Onkologii im. Prof. F. Lukaszczyka w Bydgoszczy - Dept of Chemotherapy

Bydgoszcz, , Poland

Site Status

Szpitale Pomorskie spó

Gdynia, , Poland

Site Status

Jagiellonskie Centrum Innowacji Sp. z o.o. - Centrum Bada

Krakow, , Poland

Site Status

Instytut MSF Sp.z.o.o

Lodz, , Poland

Site Status

Europejskie Centrum Zdrowia - Oddzial Onkologii

Otwock, , Poland

Site Status

MICS Centrum Medyczne Torun - Medicovernn

Torun, , Poland

Site Status

ICO Badalona - Hospital Universitari Germans Trias i Pujol - Servicio de Oncologia Medica

Badalona, , Spain

Site Status

Hospital Clinic de Barcelona - Servicio de Oncologia

Barcelona, , Spain

Site Status

Hospital Universitari Vall d'Hebron - Oncology Dept.

Barcelona, , Spain

Site Status

ICO Girona - Hospital Universitari de Girona Dr Josep Trueta - Servicio de Oncologia Medica

Girona, , Spain

Site Status

Clinica Universidad de Navarra (MAD) - Oncology Service

Madrid, , Spain

Site Status

Hospital Universitario 12 de Octubre - Servicio de Oncologia

Madrid, , Spain

Site Status

Hospital Universitario Ramon y Cajal - Servicio de Oncologia

Madrid, , Spain

Site Status

Hospital Regional Universitario de Malaga - Oncology Dept

Málaga, , Spain

Site Status

Istituto Oncologico della Svizzera Italiana (IOSI)- Ente Ospedaliero Cantonale (EOC) - Ospedale S.Giovann

Bellinzona, , Switzerland

Site Status

Kantonsspital Frauenfeld - 150509250

Frauenfeld, , Switzerland

Site Status

Kantonsspital Baselland - standort Liestal - Klinik fuer Onkologie

Liestal, , Switzerland

Site Status

Kantonsspital St. Gallen - Klinik fuer Med. Onkologie/Haematologie

Sankt Gallen, , Switzerland

Site Status

Universitaetsspital Zuerich - Klinik fuer Gynaekologie

Zurich, , Switzerland

Site Status

Addenbrooke's Hospital - Dept of Oncology

Cambridge, , United Kingdom

Site Status

Beatson West of Scotland Cancer Centre - Dept of Medical Oncology

Glasgow, , United Kingdom

Site Status

Royal Surrey County Hospital - Dept of Oncology

Guildford, , United Kingdom

Site Status

St James's University Hospital - Dept of Oncology

Leeds, , United Kingdom

Site Status

Guy's Hospital - Dept of Medical Oncology

London, , United Kingdom

Site Status

Royal Marsden Hospital-London - Dept of Haematology/Oncology Research

London, , United Kingdom

Site Status

University College London Hospitals - NIHR/Wellcome Trust

London, , United Kingdom

Site Status

The Christie Hospital - Dept of Oncology

Manchester, , United Kingdom

Site Status

Mount Vernon Hospital - Dept of Oncology

Northwood, , United Kingdom

Site Status

Royal Marsden Hospital-Sutton - Dept of Oncology (Surrey)

Sutton, , United Kingdom

Site Status

Countries

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United States Australia Belgium Denmark France Germany Israel Italy Netherlands Poland Spain Switzerland United Kingdom

Related Links

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https://medical.emdserono.com/en_US/home.html

US Medical Information website, Medical Resources

Other Identifiers

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2024-511202-23-00

Identifier Type: OTHER

Identifier Source: secondary_id

MS201924_0002

Identifier Type: -

Identifier Source: org_study_id

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