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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Neoplasms
• Intervention / Treatment: Drug: Nenocorilant 200 mg; Drug: Nivolumab; Drug: Nenocorilant 300 mg; Drug: Nenocorilant 400 mg

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.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Corcept Therapeutics; Phone Number: 650-684-0171; Email: corceptstudy750@corcept.com

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90025
      • Recruiting
      • Site 03
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Recruiting
      • Site 04
  • Texas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • Site 01
  • Utah
    • West Valley City, Utah, United States, 84119
      • Recruiting
      • Site 02

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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:

  1. Grade ≥ 3
  2. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1a: Nenocorilant 200 mg and Nivolumab; Cohort 1a: Patients will receive nenocorilant 200 mg orally under fed conditions once daily, and nivolumab 240 mg IV every 2 weeks. After 3 months of treatment, patients may choose to switch the nivolumab regimen to 480 mg IV every 4 weeks if the nenocorilant nivolumab combination is tolerated.	Drug: Nenocorilant 200 mg; Nenocorilant 200 mg will be supplied as 50 and/or 100 mg tablets.; Other Names: CORT125236; Drug: Nivolumab; Nivolumab 240 mg and 480 mg will be supplied as single-dose 120 mg/12 mL (10 mg/mL) vials.
Experimental: Cohort 1b: Nenocorilant 300 mg and Nivolumab; Cohort 1b: Patients will receive nenocorilant 300 mg orally under fed conditions once daily, and nivolumab 240 mg IV every 2 weeks. After 3 months of treatment, patients may choose to switch the nivolumab regimen to 480 mg IV every 4 weeks if the nenocorilant nivolumab combination is tolerated.	Drug: Nivolumab; Nivolumab 240 mg and 480 mg will be supplied as single-dose 120 mg/12 mL (10 mg/mL) vials.; Drug: Nenocorilant 300 mg; Nenocorilant 300 mg will be supplied as 50 and/or 100 mg tablets.; Other Names: CORT125236
Experimental: Cohort 1c: Nenocorilant 400 mg and Nivolumab; Cohort 1c: Patients will receive nenocorilant 400 mg orally under fed conditions once daily, and nivolumab 240 mg IV every 2 weeks. After 3 months of treatment, patients may choose to switch the nivolumab regimen to 480 mg IV every 4 weeks if the nenocorilant nivolumab combination is tolerated.	Drug: Nivolumab; Nivolumab 240 mg and 480 mg will be supplied as single-dose 120 mg/12 mL (10 mg/mL) vials.; Drug: Nenocorilant 400 mg; Nenocorilant 400 mg will be supplied as 50 and/or 100 mg tablets.; Other Names: CORT125236

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Patients With 1 or More Adverse Event	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	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	From first dose of study treatment up to final dose, assessed up to 9 months
Percent of Patients who Experience Dose Limiting Toxicity (DLT)	Up to 28 days after initiation of Cycle 1 (each cycle consists of 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	To evaluate the proportion of patients with measurable disease at baseline who attain a confirmed complete response (CR) or partial response (PR).	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)	To evaluate DoR as the time from the first CR or PR to first documented PD/iCPD or death or start of non-protocol-specified new anticancer therapy, whichever occurs first.	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)	To evaluate BOR as the proportion of patients with a BOR of CR, PR, stable disease (SD), PD, or nonevaluable.	From first dose until PD/iCPD or death or start of non-protocol-specified anticancer therapy, assessed up to 8 months
Duration of SD	To evaluate duration of SD as defined as the time from the start of combination treatment until the criteria for PD/iCPD are met.	Date of start of combined treatment until the criteria for PD/iCPD are met, assessed up to 8 months
Progression-Free Survival (PFS)	To evaluate progression-free survival as the time from the first dose of nenocorilant until PD/iCPD or death or start of non-protocol-specified new anticancer therapy, whichever occurs first.	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		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		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		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)

Collaborators and Investigators

• Sponsor: Corcept Therapeutics
• Investigators: Study Director: Adrian Jubb, MD, Corcept Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2026
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: December 1, 2025
• First Submitted That Met QC Criteria: December 1, 2025
• First Posted (Actual): December 11, 2025

Study Record Updates

• Last Update Posted (Actual): April 3, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Advanced Solid Tumors; Solid Tumors; Solid Malignancies
• Additional Relevant MeSH Terms: Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab
• Other Study ID Numbers: CORT125236-750

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No