A Pilot Study to Estimate Efficacy of Combining Dostarlimab and Niraparib in Patients With Relapsed EOC After Treatment With PARPi
Overview
- Phase
- Phase 2
- Intervention
- Niraparib
- Conditions
- Recurrent Ovarian Cancer
- Sponsor
- AGO Research GmbH
- Enrollment
- 100
- Primary Endpoint
- Objective Response Rate (ORR)
- Status
- Withdrawn
- Last Updated
- last year
Overview
Brief Summary
This is a multicenter, open-label, non-randomized pilot study (Phase II). The aim is to obtain evidence of efficacy of niraparib and dostarlimab (TSR-042) in patients with relapsed ovarian cancer in two experimental cohorts and to generate data on PARPi (Poly(ADP-ribose)-Polymerase inhibitor) resistance and predictive biomarkers for IO (Immuno-Oncology) and PARPi.
Detailed Description
In total, 100 patients are planned to be enrolled in 2 cohorts (60 patients cohort A and 40 patients cohort B). Cohort A: Recurrent ovarian-, fallopian tube, or primary peritoneal cancer with relapse after more than 6 months of PARPi maintenance therapy. Cohort B: Recurrent ovarian-, fallopian tube, or primary peritoneal cancer with relapse within 6 months of PARPi maintenance therapy. All patients must have a known status for BRCA1 and BRCA2 and one or two prior lines of chemotherapy. The last line of chemotherapy should have included platinum. Both cohorts will receive the selective PARP 1/2 inhibitor niraparib in combination with the anti-PD-1 checkpoint inhibitor dostarlimab (TSR-042) for a maximum treatment duration of 2 years. The overall objective of this study is to reveal insights in mechanisms of PARPi resistance in epithelial ovarian cancer (EOC) and to obtain preliminary evidence of the efficacy of sequential and/or simultaneous combined immuno-PARPi therapy.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients with secondary PARPi resistance, i.e. those whose disease has first relapsed more than 6 months after PARPi maintenance therapy
- •a. Criterion for relapse can be according to RECIST 1.1, CA-125 (GCIG) or clinical symptoms
- •Patients with primary PARPi resistance, i.e. those whose disease has relapsed within 6 months of PARPi maintenance therapy.
- •a. Criterion for relapse can be according to RECIST 1.1, CA-125 (GCIG) or clinical symptoms
- •Both cohorts
- •Patients with relapsed serous, endometrioid or clear cell epithelial ovarian cancer.
- •Histologically confirmed diagnosis (cytology alone excluded) of high-grade serous, endometrioid or clear cell ovarian carcinoma.
- •Patients with one or two prior lines of chemotherapy. The last line of chemotherapy should have included platinum.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •Estimated life expectancy of at least 3 months.
Exclusion Criteria
- •Highly symptomatic disease according to physician´s discretion, i.e. rapid remission is required.
- •Patients with mucinous endothelial ovarian cancer.
- •Non-epithelial tumor origin of the ovary, the fallopian tube or the peritoneum (e.g. germ cell tumors).
- •Ovarian tumors of low malignant potential (e.g. borderline tumors).
- •Malignancies other than ovarian cancer (EOC) within 5 years prior to registration, with the exception of those with a negligible risk of metastasis or death (e.g. 5-year OS rate \>90%) and treated with expected curative outcome (such as adequately treated non melanoma skin carcinoma, ductal carcinoma in situ, or stage I low grade uterine cancer).
- •More than two prior systemic anticancer regimens; maintenance therapies (e.g. with bevacizumab or PARPi) are not calculated as separate line.
- •More than two lines of PARPi therapies.
- •Administration of other simultaneous chemotherapy drugs, any other anticancer therapy or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial treatment period (hormonal replacement therapy is permitted).
- •The following washout requirements for prior therapies/procedures must be observed:
- •g. surgery: ≥3 weeks prior to therapy
Arms & Interventions
Cohort A
Recurrent ovarian-, fallopian tube, or primary peritoneal cancer with relapse after more than 6 months of PARPi maintenance therapy.
Intervention: Niraparib
Cohort A
Recurrent ovarian-, fallopian tube, or primary peritoneal cancer with relapse after more than 6 months of PARPi maintenance therapy.
Intervention: Dostarlimab
Cohort B
Recurrent ovarian-, fallopian tube, or primary peritoneal cancer with relapse within 6 months of PARPi maintenance therapy.
Intervention: Niraparib
Cohort B
Recurrent ovarian-, fallopian tube, or primary peritoneal cancer with relapse within 6 months of PARPi maintenance therapy.
Intervention: Dostarlimab
Outcomes
Primary Outcomes
Objective Response Rate (ORR)
Time Frame: At week 16 of treatment
Defined as Complete Response rate (CR) plus Partial Response Rate (PR) according to RECIST 1.1 assessments
Secondary Outcomes
- Response Rate(At week 16 of treatment)
- Disease Control Rate (DCR)(At 16 weeks)
- Median Progression Free Survival (PFS)(At 6 months)
- 6 months Progression Free Survival (PFS) rate(At 6 months)
- Overall Survival (OS)(At 12 months)
- Time from registration to start of first subsequent therapy (TFST)(Up to approximately 40 months)