Study of Relacorilant in Combination With Nab-Paclitaxel in Patients With Metastatic Pancreatic Ductal Adenocarcinoma

Study Overview
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Brief Summary
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This is a Phase 3, open-label study to evaluate the objective response rate (ORR), in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with relacorilant in combination with nab-paclitaxel, according to blinded independent central review.

Detailed Description
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Relacorilant is a small-molecule antagonist of the glucocorticoid receptor (GR). The goals of this study are to evaluate the efficacy, safety, and pharmacokinetics (PK) of relacorilant in combination with nab-paclitaxel in the treatment of metastatic pancreatic ductal adenocarcinoma. Eligible patients are those with mPDAC who have received at least 2 prior lines of therapy for pancreatic ductal adenocarcinoma in any setting, including at least 1 prior gemcitabine-based therapy and at least 1 prior fluoropyrimidine-based therapy. Patients will receive treatment until progressive disease (PD) (per RECIST v1.1) as determined by the Investigator, experiencing unmanageable toxicity, or until other treatment discontinuation criteria are met. All patients will be followed for documentation of disease progression and survival information (i.e., date and cause of death) and subsequent treatment.

Official Title
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A Phase 3 Study of Relacorilant in Combination With Nab-Paclitaxel in Patients With Metastatic Pancreatic Ductal Adenocarcinoma (RELIANT)

Conditions
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Metastatic Pancreatic Ductal Adenocarcinoma

Intervention / Treatment
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* Drug: Relacorilant, 100 mg and 25 mg
* Drug: Nab-paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria - Patients must have the following: Histologically confirmed PDAC with metastatic disease Received at least 2 prior lines of therapy for PDAC in any setting, including at least 1 prior gemcitabine-based therapy and at least 1 prior fluoropyrimidine-based therapy Received no more than 4 prior lines of cytotoxic or myelosuppressive therapy for PDAC A measurable lesion at baseline (within 21 days prior to the first dose of relacorilant) per RECIST v1.1, as assessed by the Investigator Willingness to provide blood samples and tumor tissue (primary or metastatic) for research purposes Karnofsky performance status (KPS) score of ≥70 Adequate gastrointestinal absorption. If the patient has undergone gastric bypass surgery and/or surgery of gastrointestinal or hepatobiliary tract, the patient must demonstrate adequate absorption as evidenced by albumin ≥3.0 g/dL, controlled pancreatic insufficiency (if present), and lack of evidence of malabsorption Adequate organ and marrow function (determined through blood and urine tests) Exclusion Criteria - Patients must not have the following: Pancreatic neuroendocrine tumors, lymphoma of the pancreas, acinar pancreatic cancer, or ampullary cancer Known untreated parenchymal brain metastasis or have uncontrolled central nervous system metastases. Patients must not require steroids and must be neurologically stable without corticosteroids for a minimum of 3 weeks prior to Cycle 1 Day 1 Clinically relevant toxicity from prior systemic cytotoxic therapies or radiotherapy that in the opinion of the Investigator has not resolved to Grade 1 or less prior to enrollment, including peripheral neuropathy that is ongoing and greater than Grade 1 in severity, according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 History of hypersensitivity or severe reaction to either relacorilant or nab-paclitaxel, or to similar classes of either drug Taken the following medications prior to enrollment: An investigational product, cytotoxic chemotherapy, or targeted agent within 14 days Radiotherapy within 21 days Palliative radiotherapy within 1 week of Cycle 1 Day 1, or if toxicities from radiotherapy are Grade 2 severity or higher or have not recovered to baseline Systemic or prescription-strength topical corticosteroids for the purposes of treating a chronic nononcologic indication within 21 days. Requirement for treatment with chronic or frequently used oral or inhaled corticosteroids for medical conditions or illnesses (e.g., rheumatoid arthritis, asthma, or immunosuppression after organ transplantation) Taking a concomitant medication that is a strong CYP3A (cytochrome P450 3A) or CYP2C8 inhibitor or inducer, or a substrate of CYP3A or CYP2C8 and has a narrow therapeutic window Concurrent treatment with mifepristone or other GR antagonists Any clinically significant uncontrolled condition(s) or any medical condition which in the opinion of the Investigator places the patient at an unacceptably high risk for toxicities or impair study participation or cooperation Any major surgery within 21 days prior to enrollment Endoscopic retrograde cholangiopancreatography with persistence of any of the following: Bilirubin ≥1.5 × ULN (Upper Limit of Normal) Amylase >2 × ULN and abdominal pain or amylase >3 × ULN (with or without symptoms) Fever or signs of infection Decreasing hemoglobin or signs of blood loss. A history of human immunodeficiency virus (HIV) or current chronic/active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV). (Patients with chronic or active hepatitis B as diagnosed by serologic tests are excluded from the study. In equivocal cases, hepatitis B or C polymerase chain reaction results may be performed and must be negative for enrollment.) A rapid decline in KPS score or serum albumin (≥20%), or have progressive pain symptoms indicative of rapid clinical deterioration, in the opinion of the Investigator, prior to enrollment. These patients will become ineligible if rapid decline is observed during the screening period.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Relacorilant with nab-paclitaxel<br>Patients will be treated with relacorilant, administered orally, once daily in combination with nab-paclitaxel on Days 1, 8, and 15 of each 28-day cycle. | Drug: Relacorilant, 100 mg and 25 mg<br>* Relacorilant is supplied as capsules for oral dosing.<br>* Other names: CORT125134;Drug: Nab-paclitaxel<br>* Nab-paclitaxel is administered as IV infusion over 30 minutes on Days 1, 8, and 15 of each 28-day cycle.<br>* Other names: Abraxane;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) | Percentage of patients with measurable disease at baseline who achieved confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as assessed by Blinded Independent Central Review (BICR). Tumor assessment consisted of computerized tomography (CT) scan or, with Sponsor approval, magnetic resonance imaging (MRI). CR was defined as disappearance of all target lesions; any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 mm. PR was defined as ≥30% decrease in the sum of the diameters (SOD) of target lesions. | Baseline and up to 32 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) Per Investigator Assessment | Percentage of patients with measurable disease at baseline who achieved confirmed CR or PR per RECIST v1.1, as assessed by the Investigator. Tumor assessment consisted of CT scan or, with Sponsor approval, MRI. CR was defined as disappearance of all target lesions; any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 mm. PR was defined as ≥30% decrease in the SOD of target lesions. | Baseline and up to 48 weeks | 
| Best Overall Response (BOR) | To evaluate the best overall response of CR, PR, stable disease (SD), or PD per RECIST v1.1. as assessed by BICR. Tumor assessment consisted of CT scan or, with Sponsor approval, MRI. CR was defined as disappearance of all target lesions; any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 mm. PR was defined as ≥30% decrease in the SOD of target lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD was defined as ≥20% increase in the SOD of target lesions or the appearance of one or more new lesions. | Baseline and up to 32 weeks | 
| Duration of Response (DOR) | To evaluate the duration of response as the time of objective response (CR or PR) to the time of disease progression or death, per RECIST v1.1 as assessed by BICR and the Investigator. Tumor assessment consisted of CT scan or, with Sponsor approval, MRI. CR was defined as disappearance of all target lesions; any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 mm. PR was defined as ≥30% decrease in the SOD of target lesions. PD was defined as ≥20% increase in the SOD of target lesions or the appearance of one or more new lesions. | Time of response up to 32 weeks | 
| Disease Control Rate (DCR) | To evaluate patients disease control rate of CR, PR, or SD at 18 weeks, per RECIST v1.1 as assessed by the Investigator. Tumor assessment consisted of CT scan or, with Sponsor approval, MRI. CR was defined as disappearance of all target lesions; any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 mm. PR was defined as ≥30% decrease in the SOD of target lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. | Enrollment through 18 weeks | 
| Progression-Free Survival (PFS) | To evaluate PFS as median time to disease progression per RECIST v1.1, or death, as assessed by BICR. Tumor assessment consisted of CT scan or, with Sponsor approval, MRI. Disease progression was defined as ≥20% increase in the SOD of target lesions or the appearance of one or more new lesions. | Baseline and up to 31 weeks. | 
| Overall Survival (OS) | To evaluate OS as median time to death by any cause. | Baseline and up to 70 weeks | 
| Progression-Free Survival (PFS) | To evaluate PFS as the percentage of patients who are progression-free at 3, 6, and 12 months per RECIST v1.1, as assessed by BICR. Tumor assessment consisted of CT scan or, with Sponsor approval, MRI. Disease progression was defined as ≥20% increase in the SOD of target lesions or the appearance of one or more new lesions. | Enrollment through 3 months, 6 months, and 12 months | 
| Overall Survival (OS) | To evaluate OS as the percentage of patients surviving at 3, 6, and 12, months. | Enrollment through 3 months, 6 months, and 12 months | 
| Cancer Antigen (CA)19-9 | To assess cancer antigen 19-9 (CA19-9) response at 8 and 16 weeks in patients who have elevated CA19-9 at baseline. Response was defined as ≥50% reduction in CA19-9. | Enrollment through 8 weeks and 16 weeks | 
| Tumor Response Per European Organization for Research and Treatment of Cancer (EORTC) Criteria | To assess tumor response based on changes in fluorodeoxyglucose-positron emission tomography (FDG-PET) scan at 6 weeks per the EORTC criteria, as assessed by BICR. | Enrollment through 6 weeks | 
| Time to Progression (TTP) | To evaluate TTP as median time to disease progression per RECIST v1.1, as assessed by the Investigator. Tumor assessment consisted of CT scan or, with Sponsor approval, MRI. Disease progression was defined as ≥20% increase in the SOD of target lesions or the appearance of one or more new lesions. | Baseline and up to 32 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pancreatic Cancer, mPDAC, Metastatic Pancreatic Ductal Adenocarcinoma, Glucocorticoid Receptor, Nab-paclitaxel, GR Antagonist, Relacorilant, Abraxane