Tuvusertib Combined With Niraparib or Lartesertib in Participants With Epithelial Ovarian Cancer (DDRiver EOC 302)
Purpose
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.
Condition
- Ovarian Cancer
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- Female
- Accepts Healthy Volunteers
- No
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
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental 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. |
|
|
Experimental 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. |
|
|
Experimental 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. |
|
|
Experimental 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. |
|
|
Experimental 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. |
|
Recruiting Locations
University of Arkansas for Medical Sciences
Little Rock, Arkansas 72205
Little Rock, Arkansas 72205
Centricity Research Cancer Center - DBA CRRI John B. Amos Cancer Center Research
Columbus, Georgia 31904
Columbus, Georgia 31904
Icahn School of Medicine at Mount Sinai PRIME - Mount Sinai - PRIME
New York, New York 10029
New York, New York 10029
More Details
- NCT ID
- NCT06433219
- Status
- Recruiting
- Sponsor
- EMD Serono Research & Development Institute, Inc.