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

NCT06433219 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: MS201924_00022024-511202-23-00
• Study Type: interventional
• Target: 63
• Locations: 13 countries
• Sites: 84

Brief Summary

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.

Conditions

Ovarian Cancer

Keywords

Ataxia telangiectasia mutated Rad3-related; Ataxia telangiectasia mutated; Poly-ADP ribose polymerase inhibitor resistance; Homologous recombination deficiency

Outcome Measures

Primary Outcomes (2)

• Part A and Part B: Confirmed Objective Response (OR) According to RECIST v1.1 as Assessed by Investigator

  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 from randomization to final assessment at end of safety follow-up visit, approximately up to 3.5 years

Secondary Outcomes (3)

• Part A and Part B: Duration of Response (DoR) According to RECIST 1.1 as Assessed by the Investigator

  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 from randomization to final assessment or until progressive disease, death, discontinuation criteria, approximately up to 3.5 years

• Part B: Overall Survival

  Time from date of randomization to death, approximately 3.5 years

Study Arms (5)

Part A, Arm 1: Tuvusertib with Niraparib

EXPERIMENTAL

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); Drug: Niraparib

Part A, Arm 2: Tuvusertib with Lartesertib

EXPERIMENTAL

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); Drug: Lartesertib (M4076)

Part B (dose optimization), dosing regimen 1 :Tuvusertib+Niraparib or Tuvusertib +Lartesertib

EXPERIMENTAL

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); Drug: Niraparib; Drug: Lartesertib (M4076)

Part B (dose optimization), dosing regimen 2: Tuvusertib + Niraparib or Tuvusertib + Lartesertib

EXPERIMENTAL

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); Drug: Niraparib; Drug: Lartesertib (M4076)

Part B: Tuvusertib Monotherapy

EXPERIMENTAL

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)

Interventions

Tuvusertib (M1774) DRUG

Tuvusertib will be administered orally.

Also known as: M1774, VXc-400, VRT-1363004, substance code MSC2584415A

Part A, Arm 1: Tuvusertib with Niraparib; Part A, Arm 2: Tuvusertib with Lartesertib; Part B (dose optimization), dosing regimen 1 :Tuvusertib+Niraparib or Tuvusertib +Lartesertib; Part B (dose optimization), dosing regimen 2: Tuvusertib + Niraparib or Tuvusertib + Lartesertib; Part B: Tuvusertib Monotherapy

Niraparib DRUG

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

Also known as: GSK3985771, MK-4827

Part A, Arm 1: Tuvusertib with Niraparib; Part B (dose optimization), dosing regimen 1 :Tuvusertib+Niraparib or Tuvusertib +Lartesertib; Part B (dose optimization), dosing regimen 2: Tuvusertib + Niraparib or Tuvusertib + Lartesertib

Lartesertib (M4076) DRUG

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

Also known as: M4076, substance code MSC2585823A

Part A, Arm 2: Tuvusertib with Lartesertib; Part B (dose optimization), dosing regimen 1 :Tuvusertib+Niraparib or Tuvusertib +Lartesertib; Part B (dose optimization), dosing regimen 2: Tuvusertib + Niraparib or Tuvusertib + Lartesertib

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: collaborator
• EMD Serono Research & Development Institute, Inc.: lead

Study Sites (84)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

University of California San Francisco - UCSF Medical Center

San Francisco, California, 94158, United States

Location

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

Columbus, Georgia, 31904, United States

Location

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

Chicago, Illinois, 60637, United States

Location

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

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

New York, New York, 10029, United States

Location

Next Oncology - Virginia

Fairfax, Virginia, 22031, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Chris O'Brien Lifehouse

Camperdown, Australia

Location

St George Private Hospital

Kogarah, Australia

Location

Liverpool Hospital - PARENT

Liverpool, Australia

Location

Cliniques Universitaires Saint-Luc - STL

Brussels, Belgium

Location

UZ Leuven

Leuven, Belgium

Location

Ålborg Universitets Hospital - PARENT

Aalborg, Denmark

Location

Rigshospitalet

Copenhagen, Denmark

Location

Sjaellands Universitetshospital - other

Odense, Denmark

Location

ICO - Site Paul Papin - service d'oncologie medicale

Angers, France

Location

Centre Francois Baclesse - Service d'Oncologie Medicale

Caen, France

Location

Centre Oscar Lambret - service de cancerologie gynecologique

Lille, France

Location

Centre Leon Berard - Service d'Oncologie Medicale

Lyon, France

Location

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

Paris, France

Location

Hopital Tenon - service d'oncologie medicale

Paris, France

Location

Hôpital Cochin - Hematologie et Oncologie Médicale

Paris, France

Location

Hôpital Européen Georges Pompidou - Hématologie Oncologie

Paris, France

Location

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

Paris, France

Location

Centre Hospitalier Lyon Sud - service d'oncologie medicale

Pierre-Bénite, France

Location

Centre de Radiotherapie Clinique Sainte Anne - 300207251

Strasbourg, France

Location

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

Strasbourg, France

Location

Institut Gustave Roussy - Oncologie Médicale

Villejuif, France

Location

Charité - Campus Virchow-Klinikum - Klinik fuer Gynaekologie

Berlin, Germany

Location

Universitaetsklinikum Bonn AoeR - Frauenklinik

Bonn, Germany

Location

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

Dresden, Germany

Location

Kliniken Essen-Mitte - Gynaekologie und Gynaekologische Onkologie

Essen, Germany

Location

Universitaetsklinikum Leipzig AoeR - Klinik und Poliklinik fuer Frauenheilkunde

Leipzig, Germany

Location

Universitaetsklinikum Muenster - Parent

Münster, Germany

Location

Universitätsklinikum Münster - Gynecology

Münster, Germany

Location

Caritas-Krankenhaus St. Josef - Klinik fuer Chirurgie

Regensburg, Germany

Location

Universitaetsklinikum Tuebingen - Parent

Tübingen, Germany

Location

Rambam Medical Center

Haifa, Israel

Location

The Lady Davis Carmel Medical Center

Haifa, Israel

Location

Hadassah University Hospital - Ein Kerem

Jerusalem, Israel

Location

Shaare Zedek

Jerusalem, Israel

Location

Chaim Sheba Medical Center

Ramat Gan, Israel

Location

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

Bologna, Italy

Location

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

Bologna, Italy

Location

Osp Cannizzaro Catania

Catania, Italy

Location

Azienda Ospedaliero-Universitaria Renato Dulbecco - Centro Oncologico

Catanzaro, Italy

Location

IEO Istituto Europeo di Oncologia - Unità Ginecologia Oncologica Medica

Milan, Italy

Location

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

Milan, Italy

Location

Istituto Nazionale Tumori Fondazione G. Pascale - Gynecology

Naples, Italy

Location

IOV - Istituto Oncologico Veneto IRCCS - Radiologia Oncologica

Padua, Italy

Location

Istituto Nazionale Tumori Regina Elena IRCCS - UOC Oncologia Medica A

Roma, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Ostetricia e ginecologia

Rome, Italy

Location

Catharina Ziekenhuis Eindhoven - Parent

Eindhoven, Netherlands

Location

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

Bydgoszcz, Poland

Location

Szpitale Pomorskie spó

Gdynia, Poland

Location

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

Krakow, Poland

Location

Instytut MSF Sp.z.o.o

Lodz, Poland

Location

Europejskie Centrum Zdrowia - Oddzial Onkologii

Otwock, Poland

Location

MICS Centrum Medyczne Torun - Medicovernn

Torun, Poland

Location

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

Badalona, Spain

Location

Hospital Clinic de Barcelona - Servicio de Oncologia

Barcelona, Spain

Location

Hospital Universitari Vall d'Hebron - Oncology Dept.

Barcelona, Spain

Location

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

Girona, Spain

Location

Clinica Universidad de Navarra (MAD) - Oncology Service

Madrid, Spain

Location

Hospital Universitario 12 de Octubre - Servicio de Oncologia

Madrid, Spain

Location

Hospital Universitario Ramon y Cajal - Servicio de Oncologia

Madrid, Spain

Location

Hospital Regional Universitario de Malaga - Oncology Dept

Málaga, Spain

Location

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

Bellinzona, Switzerland

Location

Kantonsspital Frauenfeld - 150509250

Frauenfeld, Switzerland

Location

Kantonsspital Baselland - standort Liestal - Klinik fuer Onkologie

Liestal, Switzerland

Location

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

Sankt Gallen, Switzerland

Location

Universitaetsspital Zuerich - Klinik fuer Gynaekologie

Zurich, Switzerland

Location

Addenbrooke's Hospital - Dept of Oncology

Cambridge, United Kingdom

Location

Beatson West of Scotland Cancer Centre - Dept of Medical Oncology

Glasgow, United Kingdom

Location

Royal Surrey County Hospital - Dept of Oncology

Guildford, United Kingdom

Location

St James's University Hospital - Dept of Oncology

Leeds, United Kingdom

Location

Guy's Hospital - Dept of Medical Oncology

London, United Kingdom

Location

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

London, United Kingdom

Location

University College London Hospitals - NIHR/Wellcome Trust

London, United Kingdom

Location

The Christie Hospital - Dept of Oncology

Manchester, United Kingdom

Location

Mount Vernon Hospital - Dept of Oncology

Northwood, United Kingdom

Location

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

Sutton, United Kingdom

Location

Related Links

• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources

MeSH Terms

Conditions

Ovarian Neoplasms; Hereditary Sensory and Autonomic Neuropathies

Interventions

niraparib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Study Officials

• Medical Responsible

  EMD Serono Research & Development Institute, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2024
• First Posted: May 29, 2024
• Study Start: October 30, 2024
• Primary Completion: September 29, 2025
• Study Completion (Estimated): June 26, 2026
• Last Updated: February 18, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• 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
• 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.

Locations

CH (5); GB (10); DK (3); FR (13); US (9); DE (9); IL (5); IT (10); NL (1); PL (6); ES (8); AU (3); BE (2)