A Study to Evaluate Rucaparib in Combination With Nivolumab in Patients With Selected Solid Tumors (ARIES)

Study Overview
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Brief Summary
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This is an open label Phase 2, 2-stage, 2-cohort study to evaluate rucaparib in combination with nivolumab in patients with high-grade serous or endometroid ovarian cancer. Patients entering the following cohorts must have BRCA mutational status confirmed by a central lab: Cohort A1: No BRCA mutation in tumor; high level of LOH (loss of heterozygosity) Cohort A2: BRCA mutation in tumor

Official Title
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A Phase 2, Open-label Study to Evaluate Rucaparib in Combination With Nivolumab in Patients With Selected Solid Tumors (ARIES)

Conditions
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Epithelial Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Carcinoma, High Grade Serous Carcinoma, Endometrioid Adenocarcinoma

Intervention / Treatment
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* Drug: Rucaparib
* Drug: Nivolumab


Participation Criteria
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Eligibility Criteria
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General Inclusion Criteria: ≥ 18 years of age Adequate organ function Life expectancy ≥ 16 weeks Women of childbearing potential must have a negative serum pregnancy test High-grade serous or endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer Received 1 or 2 prior regimens, including ≥ 1 prior platinum-based therapy and have platinum-sensitive disease Relapsed/progressive disease (confirmed by radiologic assessment) Willing and able to have a biopsy of tumor at screening and after 4 weeks of treatment. Measurable disease (RECIST v1.1)- Cohort A1 only ECOG performance status of 0 to 1 General Exclusion Criteria Active second malignancy Central nervous system brain metastases Evidence of interstitial lung disease, active pneumonitis, myocarditis, or history of myocarditis. Active, known or suspected autoimmune disease (eg, autoimmune hepatitis). Condition requiring systemic treatment with either corticosteroids Prior treatment with a PARP inhibitor or immune checkpoint inhibitor. Non-epithelial tumors (pure sarcomas) or ovarian tumors with low malignant potential (ie, borderline tumors) or mucinous tumors. Mixed Mullerian tumors/carcinosarcomas are allowed.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A: Ovarian Cancer Cohort<br>Oral rucaparib and Intravenous (IV) nivolumab (combination therapy) Cohort A1 Cohort A2 | Drug: Rucaparib<br>* Oral rucaparib will be administered twice daily<br>* Other names: CO-338;Drug: Nivolumab<br>* IV nivolumab will be administered once every 4 weeks<br>* Other names: BMS-936558;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) by RECIST v1.1 as Assessed by the Investigator | Objective response rate (ORR) is defined as the percentage of patients with a best confirmed response of complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as assessed by the investigator. | From enrollment until disease progression (up to approximately 2 years) | 
| The Effect of Rucaparib on the Immune Microenvironment | Change in expression of the immune marker PD-L1 pre and post-rucaparib treatment; Cohort A2 only | From enrollment to primary completion of study (up to approximately 2 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR by RECIST v1.1 and Gynecological Cancer InterGroup (GCIG) Cancer Antigen 125 (CA-125 Criteria) | Objective Response Rate (ORR) is defined as the percentage of patients with a best confirmed response of complete response (CR) or partial response (PR) by RECIST v1.1 as assessed by the investigator or a confirmed response per Gynecological Cancer InterGroup (GCIG) cancer antigen 125 (CA-125 criteria) | For patients with measurable disease, every 8 weeks after the start of combination treatment for 3 years, then every 24 weeks thereafter until disease progression or up to 25 months. Study data collection expected to last for 2 years. | 
| Progression-free Survival (PFS) | Progression-Free Survival (PFS) is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST, as determined by the investigator or death due to any cause, whichever occurs first. | From randomization until disease progression (up to approximately 2 years) | 
| Duration of Response (DOR) | Duration of response (DOR) for any confirmed RECIST CR or PR measured from the date of the first response until the first date that progressive disease (PD) is documented. | For patients with measurable disease, every 12 weeks after the start of combination treatment for 3 years, then every 24 weeks thereafter until disease progression. Study data collection expected to last for 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PARP, PARPi, PARP inhibitor, ARIES, Opdivo, Rucaparib, Nivolumab, PD-1, BRCA, LOH, CO-338, Clovis Oncology, Rubraca, Immunotherapy, BMS-936558, Clovis