Two Part Study of Nenocorilant Combined With Nivolumab in Patients With Advanced Solid Malignancies

This is a Phase 1b/2 study that consists of 2 parts.

In the dose-finding Phase 1b part, researchers will evaluate escalating dose levels of nenocorilant (given with a fixed dose and schedule of nivolumab) in patients with advanced solid malignancies. All patients will be treated with the combination of nenocorilant plus nivolumab in 28-day cycles. Nenocorilant will be administered orally once daily using a continuous dosing schedule, under fed conditions. Nivolumab will be initially given at 240 mg administered intravenously (IV) once every 2 weeks. After 3 months of treatment, patients may choose to switch to a fixed dosing regimen of 480 mg IV once every 4 weeks if they tolerate the combination regimen of nenocorilant plus nivolumab.

The proof-of-concept Phase 2 part of this study is optional and may be added to further evaluate combination treatment in patients with advanced solid malignancies.

Inclusion criteria

Part 1

• Signed and dated institutional review board (IRB)/ independent ethics committee (IEC)-approved informed consent form (ICF)
• Has solid malignancies that have received all available standard therapies for the specific tumor type or for which no standard therapy exists, unless patient is intolerant of treatment
• Has a life expectancy of ≥ 3 months
• Has evaluable disease based on RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Has adequate organ function
• Negative serum or urine pregnancy test for female patients of childbearing potential
• Agreement to use appropriate precautions to avoid pregnancy, unless the patient and/or their sole sexual partner is permanently sterilized

Exclusion criteria

Part 1

• Past or current immune-related adverse events (irAEs) due to anti-programmed cell death protein 1 ligand 1 (PD[L]1) therapy that meet any of the following criteria:

• Grade ≥ 3
• Resulted in discontinuation of anti-PD(L)1 therapy
• Medical history of an autoimmune or inflammatory disease requiring immunosuppressive therapy
• Medical history of adrenal insufficiency
• Has had any major surgery within 4 weeks prior to the first dose of study treatment
• Concurrent treatment with mifepristone or another glucocorticoid receptor (GR) modulator
• Unable to swallow, retain, or absorb oral medication
• Concurrent participation in another interventional clinical trial
• Has toxicities due to prior therapies that are reversible and have not resolved
• Requirement for treatment with prohibited medications, including but not limited to systemic corticosteroids and cytochrome P450(CYP)3A inducers or inhibitors
• Has a known history of severe hypersensitivity to any of the study drugs, or other human/humanized monoclonal antibodies
• Pregnant or lactating patients or female patients expecting to conceive children within the projected duration of the trial
• Has clinically significant uncontrolled condition(s) which, in the opinion of the Investigator, may confound the results of the trial or interfere with the patient's safety or participation
• Known psychiatric disorder that would interfere with trial compliance
• Has infection with HIV, hepatitis C virus, or hepatitis B virus
• Has untreated parenchymal brain metastasis or has uncontrolled central nervous system metastases
• Has a history of another malignancy within 2 years prior to study treatment, unless cured
• Has received prior autologous or allogeneic organ or tissue transplantation
• A QTcF interval >450 msec, a family history of long QT syndrome or unexplained sudden death at young age, or a requirement for use of medication that may prolong the QTc interval