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.
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
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
50
Nenocorilant 200 mg will be supplied as 50 and/or 100 mg tablets.
Nenocorilant 300 mg will be supplied as 50 and/or 100 mg tablets.
Nenocorilant 400 mg will be supplied as 50 and/or 100 mg tablets.
Site 03
Los Angeles, California, United States
RECRUITINGSite 05
Chicago, Illinois, United States
RECRUITINGSite 04
Grand Rapids, Michigan, United States
RECRUITINGNumber 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)
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).
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)
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 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)
To evaluate BOR as the proportion of patients with a BOR of CR, PR, stable disease (SD), PD, or nonevaluable.
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Nivolumab 240 mg and 480 mg will be supplied as single-dose 120 mg/12 mL (10 mg/mL) vials.
Site 01
San Antonio, Texas, United States
RECRUITINGSite 02
West Valley City, Utah, United States
RECRUITINGTime 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
To evaluate duration of SD as defined as the time from the start of combination treatment until the criteria for PD/iCPD are met.
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)
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.
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)