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) with
glucocorticoid (GC) excess.
Eligible patients are those with advanced ACC associated with GC excess.
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.
Inclusion Criteria: Patients must have the following:
- Histologically or cytologically confirmed ACC (advanced unresectable and/or
- Measurable disease based upon RECIST v1.1 as determined by the Investigator.
- Tumor accessible for biopsy and consent to biopsies.
- Documented GC excess.
- If received mitotane, have a mitotane level <4mg/L at screening. Note: The mitotane
level may be screened/retested multiple times to confirm that the level is trending
down and reaches the protocol eligibility requirement.
- 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
Cycle 1 Day -3 Visits (before the patient can receive study treatment).
Exclusion Criteria: Patients must not have the following:
- Major surgery within 4 weeks prior to enrollment. If the participant underwent major
surgery, they must have recovered adequately prior to starting study treatment.
- Prior treatment with a programmed cell death protein 1 (anti-PD-1),PD-1 Ligand 1
(anti-PD-L1), or PD-1 Ligand 2 (anti-PD-L2) therapy.
- Prior therapy with anti-Cluster of Differentiation (CD)137, cytotoxic
T-lymphocyte-associated (CTLA) proteinCTLA-4 antibody (including ipilimumab or any
other antibody or drug specifically targeting T-cell stimulation or checkpoint
- Taking a concomitant medication that is a strong Cytochrome P450 (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
- Requirement for chronic systemic GC treatment, such as active autoimmune disease
requiring systemic treatment (corticosteroids or other immunosuppressive medication)
- 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. Systemic (oral or injectable) regular use, or prescription topical
glucocorticoids within 28 days. Short courses (≤5 days) for noncancer-related
reasons are allowed if clinically required (such as prophylaxis for CT).
4. Mifepristone or other GR antagonists within 21 days
5. Adrenostatic medications (e.g., ketoconazole, metyrapone, or fluconazole within
14 days; or etomidate within 7 days)
- 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, nonmuscle 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
6 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.