A Study in Ovarian Cancer Patients Evaluating Rucaparib and Nivolumab as Maintenance Treatment Following Response to Front-Line Platinum-Based Chemotherapy

Study Overview
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Brief Summary
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This is a Phase 3, randomized, multinational, double-blind, dual placebo-controlled, 4-arm study evaluating rucaparib and nivolumab as maintenance treatment following response to front-line treatment in newly diagnosed ovarian cancer patients. Response to treatment will be analyzed based on homologous recombination (HR) status of tumor samples.

Official Title
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ATHENA (A Multicenter, Randomized, Double-Blind, Placebo- Controlled Phase 3 Study in Ovarian Cancer Patients Evaluating Rucaparib and Nivolumab as Maintenance Treatment Following Response to Front-Line Platinum-Based Chemotherapy)

Conditions
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Epithelial Ovarian Cancer, Primary Peritoneal, Fallopian Tube Cancer, Newly Diagnosed, FIGO Stage III-IV, Partial Response, Complete Response

Intervention / Treatment
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* Drug: Rucaparib
* Drug: Nivolumab
* Drug: Placebo Oral Tablet
* Drug: Placebo IV Infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed advanced (FIGO stage III-IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer. Completed cytoreductive surgery, including at least a bilateral salpingo-oophorectomy and partial omentectomy, either prior to chemotherapy (primary surgery) or following neoadjuvant chemotherapy (interval debulking) Completed first-line platinum-based chemotherapy and surgery with a response, in the opinion of the Investigator Sufficient tumor tissue for planned analysis ECOG performance status of 0 or 1 Patients must be 20 years of age to consent in Japan, Taiwan and South Korea; in all other participating countries patients must be 18 years of age to consent Exclusion Criteria: Pure sarcomas or borderline tumors or mucinous tumors Active second malignancy Known central nervous system brain metastases Any prior treatment for ovarian cancer, other than the first-line platinum regimen Evidence of interstitial lung disease or active pneumonitis Active, known or suspected autoimmune disease Condition requiring active systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>oral rucaparib + intravenous (IV) nivolumab | 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;|
| Experimental: Arm B<br>oral rucaparib+IV placebo | Drug: Rucaparib<br>* Oral rucaparib will be administered twice daily<br>* Other names: CO-338;Drug: Placebo IV Infusion<br>* IV placebo will be administered once every 4 weeks<br>|
| Experimental: Arm C<br>oral placebo+ IV nivolumab | Drug: Nivolumab<br>* IV nivolumab will be administered once every 4 weeks<br>* Other names: BMS-936558;Drug: Placebo Oral Tablet<br>* Placebo tablets will be administered twice daily<br>|
| Placebo Comparator: Arm D<br>Oral placebo + IV placebo | Drug: Placebo Oral Tablet<br>* Placebo tablets will be administered twice daily<br>Drug: Placebo IV Infusion<br>* IV placebo will be administered once every 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator assessed Progression-free survival (PFS) |  | From randomization until disease progression (up to approximately 7 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blinded independent central review (BICR) PFS |  | 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  7 years | 
| Overall Survival (OS) |  | From enrollment to primary study completion of study (up to approximately 10 years) | 
| Objective response rate (ORR) |  | 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  7 years | 
| Duration of response (DOR) |  | 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  7 years | 
| Number of participants with treatment-emergent Adverse Events (AEs) as assessed by CTCAE v4 (or higher) as a measure of safety and tolerability |  | Collected from the time patient receives first dose of study drug until post treatment safety follow-up period (up to approximately 10 years) | 
| Number of participants with serious AEs as a measure of safety and tolerability |  | Collected from the time patient receives first dose of study drug until post treatment safety follow-up period (up to approximately 10 years) | 
| Number of participants with laboratory abnormalities as a measure of safety and tolerability |  | Collected from the time patient receives first dose of study drug until post treatment safety follow-up period (up to approximately 10 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PARP inhibitor, PARPi, HRD, ATHENA, homologous recombination, DNA repair, LOH, DNA defect, DNA anomaly, Rucaparib, Nivolumab, PD-1, Immuno-, oncology, Tumor, mutational, burden, BRCA, First-line, Primary Therapy, Primary Treatment