Phase 2 Evaluation of Relacorilant, Nab-Paclitaxel, and Bevacizumab in Advanced Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Carcinoma

The primary objective of this Phase 2 study is to evaluate the **efficacy** of relacorilant in combination with nab-paclitaxel and bevacizumab in patients with advanced, epithelial ovarian, primary peritoneal, or fallopian-tube cancer. Efficacy is measured by progression-free survival (PFS) as assessed by the investigator. This is clinically relevant as PFS is a critical endpoint in oncology trials, providing insights into the treatment's ability to delay disease progression.

Secondary objectives include:

• Evaluating the objective response rate (ORR), duration of response (DoR), and clinical benefit rate (CBR) at 24 weeks.
• Assessing the probability of overall survival (OS) at 6, 12, and 18 months using Kaplan-Meier estimates.
• Assessing the safety of relacorilant treatment in combination with nab-paclitaxel and bevacizumab.

The clinical trial involves a total of **21 participants** diagnosed with **advanced epithelial ovarian, primary peritoneal, or fallopian-tube cancer**. The study population is exclusively female, with an age range that includes adults and older adults. Participants were selected based on specific inclusion criteria, such as having a confirmed histologic diagnosis of high-grade serous or endometrioid carcinoma, and a life expectancy of at least three months. The trial excludes individuals with primary platinum-refractory disease. Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. The trial population is required to have adequate organ function and must be able to comply with protocol requirements, including the ability to swallow and retain oral medication. Lifestyle considerations such as diet and physical activity are not specified, but participants must not have uncontrolled emesis. The trial does not include male subjects and involves a vulnerable population, as defined by the study criteria. The sponsor has not provided additional information regarding lifestyle factors or other demographic details.

The clinical trial is designed to evaluate the efficacy of **relacorilant** in combination with **nab-paclitaxel** and **bevacizumab** in patients with advanced, epithelial ovarian, primary peritoneal, or fallopian-tube cancer. This is a Phase II, randomized, double-blind, controlled study. The primary endpoint is progression-free survival (PFS), defined as the time from enrollment until the first documented progression of disease (PD) or death from any cause. Secondary endpoints include overall response rate (ORR), duration of response (DoR), clinical benefit rate (CBR) at 24 weeks, and overall survival (OS) assessed at 6, 12, and 18 months. Safety endpoints include the incidence of adverse events (AEs), serious adverse events (SAEs), and treatment-emergent adverse events (TEAEs).

The trial is expected to commence recruitment on July 12, 2025, and conclude by August 25, 2027. Participants will be involved in the study for the duration of their treatment period, which is determined by the progression of their disease or the occurrence of unacceptable toxicity. The study includes an initial screening visit to confirm eligibility based on inclusion criteria such as a confirmed histologic diagnosis, platinum-resistant disease, and adequate organ function. Participants will undergo regular follow-up visits to monitor treatment response and safety, with assessments conducted according to RECIST version 1.1 criteria. The end-of-study visit will occur after the completion of treatment or upon early termination due to disease progression or adverse events.

Participants are expected to remain in the study unless they experience disease progression, unacceptable toxicity, or withdraw consent. Conditions that may lead to early termination include non-compliance with protocol requirements or the investigator's decision based on the participant's best interest. The trial will ensure rigorous monitoring to maintain the integrity of the data and the safety of the participants throughout the study duration.

The clinical trial involves the administration of **relacorilant**, an experimental medication provided in the form of a soft capsule. The active substance, relacorilant, is chemically synthesized and is also known by the synonym CORT125134. The medication is administered orally with a maximum daily dose of 150 mg. The treatment period is extensive, with a maximum allowable duration specified as 999,999 days, although the exact dosing schedule within this period is not detailed. Compliance with the dosing regimen will be monitored throughout the trial.

In addition to relacorilant, the study includes the administration of **bevacizumab**, a non-experimental treatment used as a comparator. Bevacizumab is provided as a concentrate for solution for infusion and is administered via intravenous infusion. The active substance is a protein of non-human origin, and the maximum daily dose is set at 10 mg/kg. The treatment period is similarly extensive, with a maximum duration of 999,999 days, and the study involves specific relabelling for trial purposes.

Another non-experimental treatment used in the study is **paclitaxel albumin-bound**, which is provided as a powder for dispersion for infusion. This medication is also administered through intravenous infusion. The active substance is categorized under Specified Substance Group 1, and the maximum daily dose is 80 mg/m². As with the other treatments, the maximum treatment period is 999,999 days, and the product undergoes study-specific relabelling.

The efficacy of the clinical trial will be assessed primarily through **Progression-Free Survival (PFS)**, which is defined as the time from enrollment until the first documented progression of disease (PD) by RECIST version 1.1, as determined by the Investigator, or death due to any cause, whichever occurs first. Secondary efficacy endpoints include the **Objective Response Rate (ORR)**, which measures the proportion of patients with measurable disease at baseline who achieve a complete response (CR) or partial response (PR) by RECIST version 1.1. Additionally, the **Duration of Response (DoR)** will be evaluated, defined as the time from the first objective response (CR or PR) to the first documented PD or death. The **Clinical Benefit Rate (CBR)** at 24 weeks will also be assessed, representing the proportion of patients who achieve CR, PR, or stable disease (SD) for 24 weeks as per RECIST version 1.1. Overall Survival (OS) will be assessed at 6, 12, and 18 months.