Tuvusertib Combined With Niraparib or Lartesertib in Participants With Epithelial Ovarian Cancer (DDRiver EOC 302)
Phase 2
Active, not recruiting
- Conditions
- Ovarian Cancer
- Interventions
- Registration Number
- NCT06433219
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 63
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A, Arm 1: Tuvusertib with Niraparib Tuvusertib (M1774) In Part A, participants will be randomized to one of 2 arms to receive tuvusertib in combination with either niraparib or lartesertib. Part A, Arm 1: Tuvusertib with Niraparib Niraparib In Part A, participants will be randomized to one of 2 arms to receive tuvusertib in combination with either niraparib or lartesertib. Part B (dose optimization), dosing regimen 1 :Tuvusertib+Niraparib or Tuvusertib +Lartesertib Lartesertib (M4076) 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. Part B (dose optimization), dosing regimen 2: Tuvusertib + Niraparib or Tuvusertib + Lartesertib Tuvusertib (M1774) 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. Part B (dose optimization), dosing regimen 2: Tuvusertib + Niraparib or Tuvusertib + Lartesertib Lartesertib (M4076) 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. Part A, Arm 2: Tuvusertib with Lartesertib Tuvusertib (M1774) In Part A, participants will be randomized to one of 2 arms to receive tuvusertib in combination with either niraparib or lartesertib. Part A, Arm 2: Tuvusertib with Lartesertib Lartesertib (M4076) In Part A, participants will be randomized to one of 2 arms to receive tuvusertib in combination with either niraparib or lartesertib. Part B (dose optimization), dosing regimen 1 :Tuvusertib+Niraparib or Tuvusertib +Lartesertib Tuvusertib (M1774) 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. Part B (dose optimization), dosing regimen 1 :Tuvusertib+Niraparib or Tuvusertib +Lartesertib Niraparib 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. Part B (dose optimization), dosing regimen 2: Tuvusertib + Niraparib or Tuvusertib + Lartesertib Niraparib 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. Part B: Tuvusertib Monotherapy Tuvusertib (M1774) 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.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 OS is defined as the time from randomization to death due to any cause.
Trial Locations
- Locations (84)
University of California San Francisco - UCSF Medical Center
🇺🇸San Francisco, California, United States
University of Chicago Comprehensive Cancer Center at Silver Cross - Carolyn J. Czerkies Pavilion
🇺🇸Chicago, Illinois, United States
University of Michigan Rogel Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Virginia Cancer Specialists, PC
🇺🇸Fairfax, Virginia, United States
Chris O'Brien Lifehouse
🇦🇺Camperdown, Australia
St George Private Hospital
🇦🇺Kogarah, Australia
Hôpital Européen Georges Pompidou - Hématologie Oncologie
🇫🇷Paris, France
Universitaetsklinikum Bonn AoeR - Frauenklinik
🇩🇪Bonn, Germany
Kliniken Essen-Mitte - Gynaekologie und Gynaekologische Onkologie
🇩🇪Essen, Germany
Universitätsklinikum Münster - Gynecology
🇩🇪Münster, Germany
Scroll for more (74 remaining)University of California San Francisco - UCSF Medical Center🇺🇸San Francisco, California, United States