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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 5
- 主要终点
- Number of Patients With 1 or More Adverse Event
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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:
- •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
研究组 & 干预措施
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.
干预措施: Nenocorilant 200 mg (Drug)
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.
干预措施: Nenocorilant 300 mg (Drug)
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.
干预措施: Nenocorilant 400 mg (Drug)
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.
干预措施: Nivolumab (Drug)
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.
干预措施: Nivolumab (Drug)
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.
干预措施: Nivolumab (Drug)
结局指标
主要结局
Number of Patients With 1 or More Adverse Event
时间窗: 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
时间窗: 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
时间窗: From first dose of study treatment up to final dose, assessed up to 9 months
Percent of Patients who Experience Dose Limiting Toxicity (DLT)
时间窗: Up to 28 days after initiation of Cycle 1 (each cycle consists of 28 days)
次要结局
- 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)
- 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)
- 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)
- Duration of SD(Date of start of combined treatment until the criteria for PD/iCPD are met, assessed up to 8 months)
- 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)
- 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))