Neoplasms
Conditions
Keywords
Advanced Solid Tumors, Solid Tumors, Solid Malignancies
Brief summary
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
DRUGNenocorilant 200 mg
Nenocorilant 200 mg will be supplied as 50 and/or 100 mg tablets.
DRUGNenocorilant 300 mg
Nenocorilant 300 mg will be supplied as 50 and/or 100 mg tablets.
DRUGNenocorilant 400 mg
Nenocorilant 400 mg will be supplied as 50 and/or 100 mg tablets.
DRUGNivolumab
Nivolumab 240 mg and 480 mg will be supplied as single-dose 120 mg/12 mL (10 mg/mL) vials.
Sponsors
Corcept Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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) |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | — |
| Duration of Response (DoR) | Time of first objective response until PD/iCPD or death or start of non-protocol-specified new anticancer therapy, assessed up to 8 months | 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. |
| Objective Response Rate (ORR) | 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 | To evaluate the proportion of patients with measurable disease at baseline who attain a confirmed complete response (CR) or partial response (PR). |
| Best Overall Response (BOR) | From first dose until PD/iCPD or death or start of non-protocol-specified anticancer therapy, assessed up to 8 months | To evaluate BOR as the proportion of patients with a BOR of CR, PR, stable disease (SD), PD, or nonevaluable. |
| Duration of SD | Date of start of combined treatment until the criteria for PD/iCPD are met, assessed up to 8 months | To evaluate duration of SD as defined as the time from the start of combination treatment until the criteria for PD/iCPD are met. |
| Progression-Free Survival (PFS) | Date of first dose until PD/iCPD or death or start of non-protocol-specified new anticancer therapy, assessed up to 8 months | 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. |
Countries
United States
Contacts
CONTACTCorcept Therapeutics
STUDY_DIRECTORCamille Renard
Corcept Therapeutics
Outcome results
None listed