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

Official title

A Phase 1b/2, Open-Label, Dose-Finding and Proof of Concept Study of Nenocorilant in Combination With Anti-Programmed Cell Death/(Ligand) 1 in Patients With Advanced Solid Malignancies

Overview

This open-label, dose-finding, and proof of concept study will evaluate the safety, tolerability, maximum-tolerated dose (MTD) and/or optimal dose of nenocorilant when administered in combination with nivolumab in patients with advanced solid malignancies.

Detailed description

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.

Interventions

• Drug Nenocorilant 200 mg
  Nenocorilant 200 mg will be supplied as 50 and/or 100 mg tablets.
• Drug Nenocorilant 300 mg
  Nenocorilant 300 mg will be supplied as 50 and/or 100 mg tablets.
• Drug Nenocorilant 400 mg
  Nenocorilant 400 mg will be supplied as 50 and/or 100 mg tablets.
• Drug Nivolumab
  Nivolumab 240 mg and 480 mg will be supplied as single-dose 120 mg/12 mL (10 mg/mL) vials.

Primary outcome measures

• Number of Patients With 1 or More Adverse Event [Time frame: From first dose of study treatment up to 28 days after final dose, assessed up to 9 months]
• Number of Patients With 1 or More Serious Adverse Events [Time frame: From first dose of study treatment up to 28 days after final dose, assessed up to 9 months]
• Number of Patients With 1 or More Adverse Events Leading to Study Drug Discontinuation [Time frame: From first dose of study treatment up to final dose, assessed up to 9 months]
• Percent of Patients who Experience Dose Limiting Toxicity (DLT) [Time frame: Up to 28 days after initiation of Cycle 1 (each cycle consists of 28 days)]

Secondary outcome measures (8)

• Objective Response Rate (ORR) [Time frame: From date of first dose to progressive disease (PD)/confirmed PD using immune Response Evaluation Criteria in Solid Tumors (iRECIST) (iCPD) or death or start of non-protocol-specified new anticancer therapy, assessed up to 8 months]
• Duration of Response (DoR) [Time frame: Time of first objective response until PD/iCPD or death or start of non-protocol-specified new anticancer therapy, assessed up to 8 months]
• Best Overall Response (BOR) [Time frame: From first dose until PD/iCPD or death or start of non-protocol-specified anticancer therapy, assessed up to 8 months]
• Duration of SD [Time frame: Date of start of combined treatment until the criteria for PD/iCPD are met, assessed up to 8 months]
• Progression-Free Survival (PFS) [Time frame: Date of first dose until PD/iCPD or death or start of non-protocol-specified new anticancer therapy, assessed up to 8 months]
• Change from Baseline of Fridericia-Corrected QT (QTcF) Interval [Time frame: Baseline to End of Treatment, assessed up to 8 months]
• Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24) of Nenocorilant [Time frame: Cycle 1 Day 15 predose and 1, 2, 3, 4, and 6 hours postdose and Cycle 2 Day 1 predose (each cycle consists of 28 days)]
• Maximum Observed Plasma Concentration (Cmax) of Nenocorilant [Time frame: Cycle 1 Day 15 predose and 1, 2, 3, 4, and 6 hours postdose and Cycle 2 Day 1 predose (each cycle consists of 28 days)]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 4 centers

• Site 03 — Los Angeles
• Site 04 — Grand Rapids
• Site 01 — San Antonio
• Site 02 — West Valley City

Identifiers

NCT: NCT07276373 · CORT125236-750

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗