Phase 3 Study of Rucaparib and Nivolumab as Maintenance Therapy in Advanced High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

The primary objective of this study is to evaluate **progression-free survival** (PFS) using the Response Evaluation Criteria in Solid Tumors (RECIST), as assessed by the investigator. This evaluation will be conducted through separate comparisons: Monotherapy, comparing Arm B (oral rucaparib + intravenous placebo) with Arm D (placebo, both oral and IV) in homologous recombination deficiency (HRD) and intent-to-treat (ITT) subpopulations; and Combination, comparing Arm A (oral rucaparib + IV nivolumab) with Arm B (oral rucaparib + IV placebo) in the ITT population. This is clinically relevant as it aims to determine the efficacy of rucaparib and nivolumab as maintenance treatments in patients with advanced high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who have responded to front-line platinum-based chemotherapy.

Secondary objectives include: evaluating PFS by RECIST, as assessed by blinded independent central review (BICR); evaluating survival benefit; assessing the objective response rate (ORR) and duration of response (DOR), as assessed by the investigator, in patients with measurable disease at baseline; and evaluating safety. These objectives are crucial for understanding the broader impact of the treatment on patient outcomes and safety profiles.

The clinical trial involves a total of **743 participants** who are exclusively **female**. The study population comprises individuals aged **18 years and older**, with a specific focus on those diagnosed with advanced (FIGO stage III-IV), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer. Participants have previously responded to front-line platinum-based chemotherapy. The selection process for the trial population was based on specific inclusion criteria, including adequate organ function and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Participants were required to have completed cytoreductive surgery and first-line platinum-based chemotherapy with a response, as determined by the investigator. The trial does not include a vulnerable population, and lifestyle factors such as diet and physical activity were not specified as part of the selection criteria. The sponsor did not provide information on any additional lifestyle considerations or habits of the participants.

The clinical trial is designed as a **randomized, double-blind, placebo-controlled Phase 3 study** to evaluate the efficacy of **rucaparib** and **nivolumab** as maintenance treatment in patients with advanced high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who have responded to front-line platinum-based chemotherapy. The trial aims to assess progression-free survival (PFS) using the Response Evaluation Criteria in Solid Tumors (RECIST) as the primary endpoint, with secondary endpoints including overall survival and objective response rate. The study involves multiple arms, including monotherapy and combination therapy, to compare the effects of the investigational drugs against placebo.

The trial is expected to span from December 2018 to June 2027, with participants involved for a maximum treatment period of 25 months. The study includes several key visits: an initial screening visit to confirm eligibility based on inclusion criteria such as adequate organ function and ECOG performance status, followed by randomization within 8 weeks of the last chemotherapy cycle. Participants will undergo regular follow-up visits to monitor safety, efficacy, and any adverse events, with assessments including tumor scans and laboratory tests. The end-of-study visit will conclude the participant's involvement, with final evaluations to determine the overall outcomes of the treatment.

Participants may be withdrawn from the study early if they experience disease progression, unacceptable toxicity, or if they withdraw consent. The trial's design ensures that clinical supplies are specifically labeled and packaged for study use, with commercial supplies not utilized. The investigational products include Rubraca film-coated tablets and Opdivo concentrate for solution for infusion, with corresponding placebos for each. The study's rigorous methodology and comprehensive design aim to provide valuable insights into the potential benefits of maintenance therapy in this patient population.

The clinical trial involves the administration of **Rubraca**, a pharmaceutical product containing the active substance **rucaparib**. Rubraca is available in three different dosages: 200 mg, 250 mg, and 300 mg, all in the form of film-coated tablets. The medication is administered orally. The maximum daily dose of Rubraca is 1200 mg, and the treatment period extends up to 25 days. Clinical supplies of Rubraca will be specifically labeled and packaged for the study, ensuring that commercial supplies are not utilized. Participant compliance with the dosing schedule will be monitored throughout the trial.

Another experimental medication used in the trial is **OPDIVO**, which contains the active substance **nivolumab**. OPDIVO is provided as a 10 mg/mL concentrate for solution for infusion and is administered intravenously. The maximum daily dose for OPDIVO is 480 mg, with a treatment period of up to 24 days. Similar to Rubraca, OPDIVO will be labeled and packaged for exclusive use in the study, with no commercial supplies being used. Compliance with the administration schedule will be closely monitored.

The study also includes the use of placebos to maintain the double-blind nature of the trial. A placebo for Rubraca and a placebo for OPDIVO are utilized, with no active substances present. These placebos are designed to match the appearance and administration routes of their respective active treatments, ensuring that neither the participants nor the investigators can distinguish between the active treatments and the placebos. The use of placebos is critical for evaluating the efficacy and safety of the experimental medications in a controlled manner.

The efficacy of the clinical trial will be assessed primarily through **progression-free survival (PFS)**, as determined by the investigator using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. This primary endpoint is defined as the time from randomization to disease progression or death from any cause, whichever occurs first. Secondary efficacy endpoints include PFS as assessed by blinded independent central review (BICR) using RECIST, overall survival, objective response rate (ORR), and duration of response (DOR). The BICR-assessed PFS will be evaluated as a stand-alone secondary endpoint, providing supportive data for the primary endpoint. ORR analyses will be conducted in patients with measurable disease at baseline, and results will be summarized with frequencies and percentages. DOR is defined as the time from the first documentation of objective response to the first documentation of disease progression or death.

Data collection for these endpoints will involve tumor scans and assessments conducted prior to the initiation of any subsequent anti-cancer treatments. The trial will utilize validated scales and criteria, such as RECIST v1.1, to ensure consistency and reliability in the measurement of efficacy parameters. The schedule for these assessments will be aligned with the trial's protocol, ensuring timely and accurate data collection throughout the study duration. Safety analysis will also be conducted, encompassing adverse events, clinical laboratory results, vital signs, ECOG performance status, body weight, and concomitant medications or procedures.