Clinical trial NCT06433219: Tuvusertib Combined With Niraparib or Lartesertib in Participants With Epithelial Ovarian Cancer (DDRiver EOC 302)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Ovarian Cancer
Keywords: Ataxia telangiectasia mutated Rad3-related
Ataxia telangiectasia mutated
Poly-ADP ribose polymerase inhibitor resistance
Homologous recombination deficiency
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2024-05-29
Enrollment: 60
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Confirmed Objective Response (OR) According to RECIST v1.1 as Assessed by Investigator
timeFrame: Time from randomization to final assessment or until progressive disease, death, discontinuation criteria, approximately up to 3.5 years.
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs and Related TEAEs
timeFrame: Time from randomization to final assessment at end of safety follow-up visit, approximately up to 3.5 years.
Secondary outcomes:
measure: Duration of Response (DoR) According to RECIST 1.1 as Assessed by the Investigator
timeFrame: Time from randomization to final assessment or until progressive disease, death, discontinuation criteria, approximately up to 3.5 years.
measure: Progression Free Survival (PFS) According to RECIST 1.1 as Assessed by the Investigator
timeFrame: Time from randomization to final assessment or until progressive disease, death, discontinuation criteria, approximately up to 3.5 years.
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Columbus
country: United States
facility: Centricity Research Cancer Center - DBA CRRI John B. Amos Cancer Center Research
state: Georgia
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai PRIME - Mount Sinai - PRIME
state: New York
city: Fairfax
country: United States
facility: Next Oncology - Virginia
state: Virginia
city: Liverpool
country: Australia
facility: Liverpool Hospital - PARENT
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc - STL
city: Leuven
country: Belgium
facility: UZ Leuven
city: Aalborg
country: Denmark
facility: Ålborg Universitets Hospital - PARENT
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Odense
country: Denmark
facility: Sjaellands Universitetshospital - other
city: Angers Cedex 2
country: France
facility: ICO - Site Paul Papin - service d'oncologie medicale
city: Caen Cedex 05
country: France
facility: Centre Francois Baclesse - Service d'Oncologie Medicale
city: Lille cedex
country: France
facility: Centre Oscar Lambret - service de cancerologie gynecologique
city: Lyon
country: France
facility: Centre Leon Berard - Service d'Oncologie Medicale
city: Paris cedex 12
country: France
facility: Groupe Hospitalier Diaconesses - Hôpital De La Croix Saint Simon - service d'oncologie medicale
city: Paris Cedex 14
country: France
facility: Hôpital Saint Joseph - Paris - Service d'Oncologie-Cancerologie
city: Paris cedex
country: France
facility: Hopital Tenon - service d'oncologie medicale
city: Paris
country: France
facility: Hôpital Cochin - Hematologie et Oncologie Médicale
city: Pierre Benite cedex
country: France
facility: Centre Hospitalier Lyon Sud - service d'oncologie medicale
city: Strasbourg
country: France
facility: Centre de Radiotherapie Clinique Sainte Anne - 300207251
city: Strasbourg
country: France
facility: Institut de Cancérologie de Strasbourg Europe - ICANS - Service d'oncologie médicale
city: Villejuif
country: France
facility: Institut Gustave Roussy - Oncologie Médicale
city: Berlin
country: Germany
facility: Charité - Campus Virchow-Klinikum - Klinik fuer Gynaekologie
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus TU Dresden - Klinik u. Poliklinik f. Frauenheilkunde
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig AoeR - Klinik und Poliklinik fuer Frauenheilkunde
city: Muenster
country: Germany
facility: Universitaetsklinikum Muenster - Parent
city: Haifa
country: Israel
facility: The Lady Davis Carmel Medical Center
city: Jerusalem
country: Israel
facility: Hadassah University Hospital - Ein Kerem
city: Jerusalem
country: Israel
facility: Shaare Zedek
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Bologna
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS - Oncologia Medica
city: Catania
country: Italy
facility: Osp Cannizzaro Catania
city: Milano
country: Italy
facility: IEO Istituto Europeo di Oncologia - Unità Ginecologia Oncologica Medica
city: Milano
country: Italy
facility: Istituto Clinico Humanitas - U.O. di Oncologia Medica ed Ematologia
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione G. Pascale - Gynecology
city: Roma
country: Italy
facility: Istituto Nazionale Tumori Regina Elena IRCCS - UOC Oncologia Medica A
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Ostetricia e ginecologia
city: Gdynia
country: Poland
facility: Szpitale Pomorskie spó
city: Krakow
country: Poland
facility: Jagiellonskie Centrum Innowacji Sp. z o.o. - Centrum Bada
city: Lodz
country: Poland
facility: Instytut MSF Sp.z.o.o
city: Otwock
country: Poland
facility: Europejskie Centrum Zdrowia - Oddzial Onkologii
city: Torun
country: Poland
facility: MICS Centrum Medyczne Torun - Medicovernn
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona - Servicio de Oncologia
city: Girona
country: Spain
facility: ICO Girona - Hospital Universitari de Girona Dr Josep Trueta - Servicio de Oncologia Medica
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra (MAD) - Oncology Service
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre - Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal - Servicio de Oncologia
city: Bellinzona
country: Switzerland
facility: Istituto Oncologico della Svizzera Italiana (IOSI)- Ente Ospedaliero Cantonale (EOC) - Ospedale S.Giovann
city: Frauenfeld
country: Switzerland
facility: Kantonsspital Frauenfeld - 150509250
city: Liestal
country: Switzerland
facility: Kantonsspital Baselland - standort Liestal - Klinik fuer Onkologie
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen - Klinik fuer Med. Onkologie/Haematologie
city: Zuerich
country: Switzerland
facility: Universitaetsspital Zuerich - Klinik fuer Gynaekologie
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital - Dept of Oncology
city: Leeds
country: United Kingdom
facility: St James's University Hospital - Dept of Oncology
city: London
country: United Kingdom
facility: Guy's Hospital - Dept of Medical Oncology
city: London
country: United Kingdom
facility: University College London Hospitals - NIHR/Wellcome Trust
city: Manchester
country: United Kingdom
facility: The Christie Hospital - Dept of Oncology
Study officials:
affiliation: EMD Serono Research & Development Institute, Inc.
name: Medical Responsible
role: STUDY_DIRECTOR
References: