Study 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.

• Relacorilant (Drug), also known as CORT125134: Relacorilant, 100 mg soft gel capsules orally once daily
• Pembrolizumab (Drug), also known as Keytruda: Pembrolizumab 400 mg infusion every 6 weeks

Primary outcomes

• Dose-limiting Toxicity (DLT) [Up to 12 weeks]: Evaluate the percentage of patients with a dose-limiting toxicity

Secondary outcomes

• Non-Progression Rate (NPR) [24 weeks from enrollment]: Evaluate the non-progression rate (NPR) per RECIST v1.1
• Progression-Free Survival (PFS) [From date of first treatment, until the date of first documented progression or date of death from any cause, whichever came first, up to month 24]: Evaluate progression-free survival (PFS) per RECIST v1.1
• Number of Participants with Adverse Events [Up to 37 days post-treatment]: 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 in Patients with Advanced ACC and Glucocorticoid Excess [Up to 24 months]: Plasma concentrations of relacorilant in combination with pembrolizumab will be calculated in patients with advanced ACC and glucocorticoid excess

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Histologically or cytologically confirmed ACC (advanced unresectable and/or metastatic)
* Measurable disease based upon RECIST v1.1 as determined by the Investigator.
* Documented GC excess (too much cortisol).
* For patients who have received mitotane within 3 months prior to screening, mitotane levels must be <4 mg/L at screening.
* Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
* Adequate organ and bone marrow function (determined through blood and urine tests)
* Negative pregnancy test for patients of childbearing potential at the Screening and every 6 weeks (+ or - 7 days) in female patients of childbearing potential.

Exclusion Criteria:

* Major surgery within 4 weeks prior to enrollment. If the participant underwent major surgery, they must have recovered adequately prior to starting study treatment.
* Have received and responded (complete response \[CR\] or partial response \[PR\]) to prior treatment with any prior checkpoint inhibitor or any other agents targeting T-cell stimulation pathways
* Taking a concomitant medication that is a strong Cytochrome P450 3A (CYP3A) inducer, or that is a substrate of CYP3A with a narrow therapeutic index
* Known untreated parenchymal brain metastasis or have uncontrolled central nervous system (CNS) metastases. Patients must not require steroids and must be neurologically stable without corticosteroids for a minimum of 3 weeks prior to the commencement of the study. Patients with neurologic symptoms must undergo a CT/MRI to rule out occult CNS metastases.
* Requirement for chronic systemic GC treatment, such as active autoimmune disease requiring systemic treatment (corticosteroids or other immunosuppressive medication)
* Patients requiring inhaled glucocorticoids but have no other alternative treatment option if their condition deteriorates during the study.
* Clinically relevant toxicity from prior systemic cytotoxic therapies or radiotherapy that in the opinion of the Investigator has not resolved to NCI-CTCAE v5.0 Grade 1 or less prior to the first dose of relacorilant.
* Treated with the following prior to the first dose of relacorilant:

  1. Any investigational product, systemic anticancer therapy, or radiation therapy within 21 days
  2. Antibodies or anticancer vaccines within 60 days
  3. Mifepristone or other GR antagonists within 5 half-lives of these medications
  4. Adrenostatic medications within 5 half-lives of these medications
* History of severe hypersensitivity to another monoclonal antibody
* Other concurrent cancer or a history of another invasive malignancy within the last 3 years that has a likelihood of recurrence of >30% within the next 5 years. Adequately treated basal and squamous skin cancers, ductal carcinoma in situ, cervical cancer, prostate cancer, non-muscle invasive urothelial cancer or other tumors curatively treated with no evidence of disease are permissible.
* Human immunodeficiency virus (HIV) or current chronic/active infection with hepatitis C virus or hepatitis B virus including: Chronic or active hepatitis B as diagnosed by serologic tests. In equivocal cases, hepatitis B or C polymerase chain reaction may be performed and must be negative for enrollment.
* Clinically significant uncontrolled condition(s) or a condition which, in the opinion of the Investigator, may confound the results of the trial or interfere with the patient's participation, including but not limited to:

  1. Unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction 3 months before study entry.
  2. Active infection that requires parenteral antibiotics.
  3. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

• Andreas G Moraitis, MD, Study director, Corcept Therapeutics