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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (8)

• Objective Response Rate (ORR) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: From first dose until PD/iCPD or death or start of non-protocol-specified anticancer therapy, assessed up to 8 months]
• Duration of SD [Срок оценки: Date of start of combined treatment until the criteria for PD/iCPD are met, assessed up to 8 months]
• Progression-Free Survival (PFS) [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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)]

Критерии участия

Критерии включения

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

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 4 центра

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

Идентификаторы

NCT: NCT07276373 · CORT125236-750

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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