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

Phase 2

Recruiting

• Conditions: Ovarian Cancer
• Interventions: Drug: Tuvusertib (M1774); Drug: Lartesertib (M4076); Drug: Niraparib

• Registration Number: NCT06433219
• Lead Sponsor: EMD Serono Research & Development Institute, Inc.

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. The participants will previously have progressed while treated with a poly ADP ribose polymerase (PARP) inhibitor. The primary objective of the study is to assess the effect of the treatment in terms of overall response, i.e. whether the tumor disappears, shrinks, remains unchanged, or gets worse.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-05-22
• Study First Submitted QC: 2024-05-22
• Study First Posted: 2024-05-29
• Study Start: 2024-10-30
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-30
• Last Update Posted: 2025-02-03
• Primary Completion: 2028-01-10
• Study Completion: 2028-01-25

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 60

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)

• 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 last platinum administration in the 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.
• Other Protocol defined exclusion criteria could apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tuvusertib with Lartesertib	Tuvusertib (M1774)	-
Tuvusertib with Lartesertib	Lartesertib (M4076)	-
Tuvusertib with Niraparib	Tuvusertib (M1774)	-
Tuvusertib with Niraparib	Niraparib	-

Primary Outcome Measures

Name	Time	Method
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.
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 Outcome Measures

Name	Time	Method
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.
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.

Trial Locations

Locations (58)

MICS Centrum Medyczne Torun - Medicovernn; 🇵🇱 Torun, Poland

Hospital Clinic de Barcelona - Servicio de Oncologia; 🇪🇸 Barcelona, Spain

ICO Girona - Hospital Universitari de Girona Dr Josep Trueta - Servicio de Oncologia Medica; 🇪🇸 Girona, Spain

Clinica Universidad de Navarra (MAD) - Oncology Service; 🇪🇸 Madrid, Spain

Hospital Universitario 12 de Octubre - Servicio de Oncologia; 🇪🇸 Madrid, Spain

Hospital Universitario Ramon y Cajal - Servicio de Oncologia; 🇪🇸 Madrid, Spain

Istituto Oncologico della Svizzera Italiana (IOSI)- Ente Ospedaliero Cantonale (EOC) - Ospedale S.Giovann; 🇨🇭 Bellinzona, Switzerland

Kantonsspital Frauenfeld - 150509250; 🇨🇭 Frauenfeld, Switzerland

Kantonsspital Baselland - standort Liestal - Klinik fuer Onkologie; 🇨🇭 Liestal, Switzerland

Kantonsspital St. Gallen - Klinik fuer Med. Onkologie/Haematologie; 🇨🇭 St. Gallen, Switzerland

Universitaetsspital Zuerich - Klinik fuer Gynaekologie; 🇨🇭 Zuerich, Switzerland

Royal Surrey County Hospital - Dept of Oncology; 🇬🇧 Guildford, United Kingdom

St James's University Hospital - Dept of Oncology; 🇬🇧 Leeds, United Kingdom

Guy's Hospital - Dept of Medical Oncology; 🇬🇧 London, United Kingdom

The Christie Hospital - Dept of Oncology; 🇬🇧 Manchester, United Kingdom

Europejskie Centrum Zdrowia - Oddzial Onkologii; 🇵🇱 Otwock, Poland

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Icahn School of Medicine at Mount Sinai PRIME - Mount Sinai - PRIME; 🇺🇸 New York, New York, United States

Liverpool Hospital - PARENT; 🇦🇺 Liverpool, Australia

Centre Francois Baclesse - Service d'Oncologie Medicale; 🇫🇷 Caen Cedex 05, France

Centre Oscar Lambret - service de cancerologie gynecologique; 🇫🇷 Lille cedex, France

Centre Leon Berard - Service d'Oncologie Medicale; 🇫🇷 Lyon, France

Hôpital Saint Joseph - Paris - Service d'Oncologie-Cancerologie; 🇫🇷 Paris Cedex 14, France

Centre Hospitalier Lyon Sud - service d'oncologie medicale; 🇫🇷 Pierre Benite cedex, France

Centre de Radiotherapie Clinique Sainte Anne - 300207251; 🇫🇷 Strasbourg, France

Charité - Campus Virchow-Klinikum - Klinik fuer Gynaekologie; 🇩🇪 Berlin, Germany

Universitaetsklinikum Carl Gustav Carus TU Dresden - Klinik u. Poliklinik f. Frauenheilkunde; 🇩🇪 Dresden, Germany

Universitaetsklinikum Leipzig AoeR - Klinik und Poliklinik fuer Frauenheilkunde; 🇩🇪 Leipzig, Germany

Universitaetsklinikum Muenster - Parent; 🇩🇪 Muenster, Germany

The Lady Davis Carmel Medical Center; 🇮🇱 Haifa, Israel

Shaare Zedek; 🇮🇱 Jerusalem, Israel

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS - Oncologia Medica; 🇮🇹 Bologna, Italy

Istituto Clinico Humanitas - U.O. di Oncologia Medica ed Ematologia; 🇮🇹 Milano, Italy

University College London Hospitals - NIHR/Wellcome Trust; 🇬🇧 London, United Kingdom

University of Arkansas for Medical Sciences; 🇺🇸 Little Rock, Arkansas, United States

Centricity Research Cancer Center - DBA CRRI John B. Amos Cancer Center Research; 🇺🇸 Columbus, Georgia, United States

Next Oncology - Virginia; 🇺🇸 Fairfax, Virginia, United States

Cliniques Universitaires Saint-Luc - STL; 🇧🇪 Bruxelles, Belgium

UZ Leuven; 🇧🇪 Leuven, Belgium

Ålborg Universitets Hospital - PARENT; 🇩🇰 Aalborg, Denmark

Rigshospitalet; 🇩🇰 Copenhagen, Denmark

Sjaellands Universitetshospital - other; 🇩🇰 Odense, Denmark

ICO - Site Paul Papin - service d'oncologie medicale; 🇫🇷 Angers Cedex 2, France

Groupe Hospitalier Diaconesses - Hôpital De La Croix Saint Simon - service d'oncologie medicale; 🇫🇷 Paris cedex 12, France

Hopital Tenon - service d'oncologie medicale; 🇫🇷 Paris cedex, France

Hôpital Cochin - Hematologie et Oncologie Médicale; 🇫🇷 Paris, France

Institut de Cancérologie de Strasbourg Europe - ICANS - Service d'oncologie médicale; 🇫🇷 Strasbourg, France

Institut Gustave Roussy - Oncologie Médicale; 🇫🇷 Villejuif, France

Hadassah University Hospital - Ein Kerem; 🇮🇱 Jerusalem, Israel

Chaim Sheba Medical Center; 🇮🇱 Ramat Gan, Israel

Osp Cannizzaro Catania; 🇮🇹 Catania, Italy

IEO Istituto Europeo di Oncologia - Unità Ginecologia Oncologica Medica; 🇮🇹 Milano, Italy

Istituto Nazionale Tumori Fondazione G. Pascale - Gynecology; 🇮🇹 Napoli, Italy

Istituto Nazionale Tumori Regina Elena IRCCS - UOC Oncologia Medica A; 🇮🇹 Roma, Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Ostetricia e ginecologia; 🇮🇹 Rome, Italy

Szpitale Pomorskie spó; 🇵🇱 Gdynia, Poland

Jagiellonskie Centrum Innowacji Sp. z o.o. - Centrum Bada; 🇵🇱 Krakow, Poland

Instytut MSF Sp.z.o.o; 🇵🇱 Lodz, Poland