Nutritional and Metabolic Diseases

Gland and Hormone Related Diseases

All Conditions

Neoplasms

Symptoms and General Pathology

Heart and Blood Diseases

Rare Diseases

Diabetes Mellitus, Type 2

Carcinoma

Diabetes Mellitus

Syndrome

Hypertension

Cushing Syndrome

Adrenocortical Hyperfunction

Facies

Glucose Intolerance

Hyperglycemia

Adrenocortical Carcinoma

Endocrine System Diseases

Adrenal Gland Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Adrenal Cortex Neoplasms

Adrenal Gland Neoplasms

Endocrine Gland Neoplasms

Adrenal Cortex Diseases

Cushing's Syndrome

Hyperadrenalism

Anti-Inflammatory Agents

All Drugs and Chemicals

Antineoplastic Agents

Vasoconstrictor Agents

Respiratory System Agents

Hydrocortisone

Hydrocortisone 17-butyrate 21-propionate

Hydrocortisone acetate

Hydrocortisone hemisuccinate

Hormones

Pembrolizumab

Epinephrine

Glucocorticoids

Racepinephrine

Epinephryl borate

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Participants will be treated on Day -3 to Day 1 (Cohort 1 under fasting conditions) or Day -6 to Day 1 (Cohort 2 under fed conditions) for Cycle 1 only. During the lead-in period, 300 mg relacorilant will be administered daily for 4 -7 days. Patients will receive their first pembrolizumab infusion on Cycle 1 Day 1. The participants will then receive combined treatment from Cycle 1 Day 1 until confirmed PD or unacceptable toxicity. Pembrolizumab will be administered every 6 weeks (on Day 1 of each 42-day cycle) and relacorilant will be administered daily. Optional Cohort 3 will lead-in with 400 mg relacorilant once daily for 7 days and combined treatment of relacorilant and pembrolizumab, depending on PD and toxicity.

Relacorilant, 100 mg soft gel capsules orally once daily

Relacorilant

Pembrolizumab 400 mg infusion every 6 weeks

Andreas G Moraitis, MD

This study will investigate the safety and efficacy of Relacorilant in combination with Pembrolizumab for Patients with Adrenocortical Carcinoma which Produces Too Much Stress Hormone (Cortisol).

Relacorilant is a small molecule antagonist of the glucocorticoid receptor (GR).

The goal of this study is to assess the safety and efficacy of relacorilant when given in combination with pembrolizumab in patients with advanced adrenocortical carcinoma (ACC) which produces too much stress hormone (cortisol). Too much stress hormone (cortisol) is also called glucocorticoid (GC) excess.

Eligible patients are those with advanced ACC that produces too much cortisol.

Patients will receive treatment until progressive disease (PD) (per RECIST v1.1) is confirmed, experience unmanageable toxicity, or until other treatment discontinuation criteria are met. All patients will be followed for documentation of disease progression, survival information (i.e., date and cause of death) and subsequent treatment.

Study of Relacorilant in Combination With Pembrolizumab for Patients With Adrenocortical Carcinoma Which Produces Too Much Stress Hormone (Cortisol)

A Phase 1b, Open-Label Study of Relacorilant in Combination With Pembrolizumab for Patients With Adrenocortical Carcinoma With Excess Glucocorticoid Production

Evaluate the percentage of patients with a dose-limiting toxicity

Evaluate the non-progression rate (NPR) per RECIST v1.1

Evaluate progression-free survival (PFS) per RECIST v1.1

Adverse events (AEs) by severity grade using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0)

Plasma concentrations of relacorilant in combination with pembrolizumab will be calculated in patients with advanced ACC and glucocorticoid excess

Corcept Therapeutics

Digestive System Diseases

Pancreatic Neoplasms

Pancreatic Cancer

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

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.

Relacorilant is supplied as capsules for oral dosing.

Relacorilant, 100 mg and 25 mg

Nab-paclitaxel is administered as IV infusion over 30 minutes on Days 1, 8, and 15 of each 28-day cycle.

Nab-paclitaxel

William Guyer, PharmD

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.

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.

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

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

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.

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.

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.

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.

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.

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.

To evaluate OS as median time to death by any cause.

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.

To evaluate OS as the percentage of patients surviving at 3, 6, and 12, months.

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.

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.

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.

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.

Relacorilant, 100 mg and 25 mg: Relacorilant is supplied as capsules for oral dosing.

Nab-paclitaxel: Nab-paclitaxel is administered as IV infusion over 30 minutes on Days 1, 8, and 15 of each 28-day cycle.

Relacorilant With Nab-paclitaxel

Patients were treated with relacorilant, administered orally, once daily in combination with nab-paclitaxel on Days 1, 8, and 15 of each 28-day cycle.

Relacorilant, 100 mg and 25 mg: Relacorilant was supplied as capsules for oral dosing.

Nab-paclitaxel: Nab-paclitaxel was administered as IV infusion over 30 minutes on Days 1, 8, and 15 of each 28-day cycle.

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

The independent data monitoring committee found no safety issues, however the observed response rate did not meet the predefined threshold for continuing the study. The study was terminated by the Sponsor.

Medical Director

Complete response

Partial response

No response

Intent-to-Treat (ITT) Population: Patients enrolled and treated with at least 1 dose of study treatment

Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR)

Objective Response Rate (ORR) Per Investigator Assessment

Evaluable Population: Patients in the ITT population who had at least 1 post-baseline radiographic tumor assessment

Best Overall Response (BOR)

This outcome was not analyzed because the response rate was 0%.

Duration of Response (DOR)

Disease Control Rate (DCR)

Progression-Free Survival (PFS)

Overall Survival (OS)

3 months

6 months

12 months

8 weeks

16 weeks

Patients in the ITT population who had elevated CA19-9 at Baseline

Cancer Antigen (CA)19-9

Complete metabolic response

Partial metabolic response

Stable metabolic disease

Progressive metabolic disease

Patients in the ITT Population with measurable disease at baseline by FDG-PET evaluation

Tumor Response Per European Organization for Research and Treatment of Cancer (EORTC) Criteria

Time to Progression (TTP)

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Kennedy Disease

Androgens

Patients will be treated with enzalutamide monotherapy once daily for 28 days followed by combination treatment with CORT125281 at escalating dose levels and enzalutamide once daily in 28-day dosing cycles.

Patients who have progressed during treatment with abiraterone and no other AR-blocking therapies will be treated with CORT125281 and enzalutamide.

Sub-Cohort (first 10 patients enrolled into Cohort A). Patients enrolled into this subcohort will receive a single dose of CORT125281 at Cycle 1 Day -7 and a single dose of CORT125281 at Cycle 1 Day 1 30 minutes after a standard breakfast to assess the effect of food on PK parameters. Patients will then begin CORT125281 in combination with enzalutamide on Cycle 1 Day 2 and continue in 28-day dosing cycles.

Patients who progressed during treatment with enzalutamide or second-generation AR-blocking therapies will be treated with a daily dose of CORT125281 and enzalutamide.

Patients randomized to this cohort will receive enzalutamide and a titrated dose of CORT125281. Enzalutamide will be continued at the dose currently tolerated by the patient at screening.

Patients randomized to this cohort will receive enzalutamide, placebo, and CORT125281.

CORT125281 is supplied as capsules for oral dosing

CORT125281

Enzalutamide (Xtandi)

Placebo capsules to match the appearance of the CORT125281

Placebo

Grace Mann, PhD

This is an open-label, Phase 1/2a dose escalation study with an expansion phase to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD), and preliminary efficacy of CORT125281 in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) to identify a recommended dose (RD) for Phase 2 studies.

CORT125281 is a selective glucocorticoid receptor (GR) antagonist. In this study, CORT125281 will be administered orally in combination with enzalutamide to patients with metastatic castration-resistant prostate cancer (mCRPC) to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of the regimen. The study consists of two phases: a dose-determination phase and an expansion phase. The dose determination phase is designed to determine dose-limiting toxicities and the RD of CORT125281 plus enzalutamide in patients with mCRPC. Once the recommended dosing regimen has been determined, the following expansion cohorts will be enrolled and treated with CORT125281 plus enzalutamide at the recommended dose level.

Abi-Resistant Cohort: Patients who have progressed during treatment with abiraterone, and have received no other androgen receptor (AR)-blocking therapies

ARant-Resistant Cohort: Patients who have progressed during treatment with enzalutamide or other second-generation AR inhibitors.

The effect of food on CORT125281 PK will be assessed in a portion of the patients enrolled in the Expansion Phase. The two expansion cohorts will be enrolled in parallel.

In each phase of the study, routine assessments of safety and tolerability will be performed and samples will be collected to determine standard PK parameters for CORT125281, enzalutamide, and their major metabolites. PD, quality of life evaluations and preliminary evaluations of anti-tumor activity of CORT125281 with enzalutamide will be performed throughout the study.

Only patients with histologically confirmed metastatic castration-resistant prostate cancer will be considered for the study.

Study to Evaluate CORT125281 in Combination With Enzalutamide in Patients With mCRPC

Phase 1/2a Dose-Escalation and Expansion Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of CORT125281 With Enzalutamide in Patients With Metastatic Castration-Resistant Prostate Cancer

Determine the maximum tolerated dose (MTD) and/or biologically active doses of CORT125281 in combination with enzalutamide to identify the recommended dose (RD) for Phase 2 studies based on the number of patients with dose limiting toxicities (DLTs) of CORT125281 in combination with enzalutamide

The safety of each treatment group will be assessed by evaluating the incidence of treatment-related adverse events according to CTCAE v4.03

Area under the plasma concentration-time curve calculated using linear trapezoidal summation from time 0 to time last, where "last" is the time of the last measurable concentration

Area under the plasma concentration-time curve from 0 to 24 hours, calculated using linear trapezoidal summation

Area under the plasma concentration-time curve from 0 to infinity, calculated using the formula: AUC0-ing = AUC0-last + Clast/ λz, where λz is the apparent terminal elimination rate constant (whenever possible)

Minimum observed plasma concentration, at predose at steady-state

Time of the maximum plasma concentration (obtained without interpolation)

Terminal elimination rate constant (whenever possible)

Comparison of the fed state versus the fasted state comparison for the maximum observed plasma concentration (Cmax)

Comparison of the fed state versus fasted state comparison for area under the plasma concentration-time curve

Comparison of the fed state versus fasted state comparison for area under the plasma concentration-time curve to infinity

Determine the ORR by comparing the proportion of the patients who have either a complete response (CR) or partial response (PR)

Determine the proportion of patients with a reduction in PSA level by \>50%

Determine the time to SSE defined as symptomatic fracture, radiation or surgery to bone, or spinal cord compression

Determine rPFS defined as the time interval from first dose of study drug (CORT125281 and/or enzalutamide) to the date when the first site of disease is found to progress on CT, MRI, or radionucleotide bone scan per PCWG3, or death whichever occurs first; including the proportion of patients progression-free at 4, 6, and 12 months

Assess time to PSA progression, including the proportion of patients progression free at 4, 6, and 12 months

Assess time to clinical progression, including the proportion of patients progression free at 4, 6, and 12 months

Determine the DOR by the time from the first occurrence of a documented objective tumor response to the time of radiographic progression (per investigator using RECIST v1.1) or death from any cause on study, whichever occurs first

Determine OS by the time from the first dose of study drug (CORT125281 and/or enzalutamide) to the date of death from any cause

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Relacorilant in Combination With Pembrolizumab for Patients With Adrenocortical Carcinoma Which Produces Too Much Stress Hormone (Cortisol)	NCT04373265	Adrenocortical ...	Relacorilant Pembrolizumab	18 Years -	Corcept Therapeutics
Study of Relacorilant in Combination With Nab-Paclitaxel in Patients With Metastatic Pancreatic Ductal Adenocarcinoma	NCT04329949	Metastatic Panc...	Relacorilant, 1... Nab-paclitaxel	18 Years -	Corcept Therapeutics
Study of Relacorilant in Combination With Nab-Paclitaxel in Patients With Metastatic Pancreatic Ductal Adenocarcinoma	NCT04329949	Metastatic Panc...	Relacorilant, 1... Nab-paclitaxel	18 Years -	Corcept Therapeutics
Study to Evaluate CORT125281 in Combination With Enzalutamide in Patients With mCRPC	NCT03437941	Metastatic Cast...	CORT125281 Enzalutamide (X... Placebo	18 Years -	Corcept Therapeutics

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