A Study of HG381 Administered to Patients With Advanced Solid Tumors

Официальное название

Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of HG381 as Monotherapy in Patients With Advanced Solid Tumors

Обзор

This is a Phase I, first in human, open-label, non-randomized, multicenter study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, preliminary efficacy and establish a recommended dose of HG381 administered intravenously (IV) alone in subjects with advanced solid tumors.

Подробное описание

The trial consists of a dose escalation phase and a cohort expansion phase.In dose escalation phase, escalating doses of HG381 will be evaluated as guided by the traditional 3+3 design . In cohort expansion phase, subjects will receive HG381 alone at a single dose level determined based on the data form dose escalation phase. In total, approximately 57 subjects will participate in the study, approximately 42 in the dose-escalation cohort, and approximately 15 in the expansion cohort.

Вмешательства

• Препарат HG381
  HG381 is available as white to off-white cake or powder for solution for injection at a unit dose strength of 5 mg per vial. HG381 will be administered as IV injection.

Первичные конечные точки

• Number of subjects achieving Dose-limiting toxicity (DLT) [Срок оценки: Up to Day 21]
• Maximum Tolerated Dose (MTD) [Срок оценки: Up to 12 months]
• Number of subjects with adverse events (AEs) and serious adverse events (SAEs) [Срок оценки: Up to 24 months]
• Severity of AEs [Срок оценки: Up to 24 months]

Вторичные конечные точки (6)

• Recommended Phase 2 Dose (RP2D) of HG381 [Срок оценки: Up to 12 months]
• Best objective response based on RECIST 1.1 [Срок оценки: Up to 24 months]
• HG381 concentrations in plasma following administration of HG381 alone [Срок оценки: Cycle 1 Days 1, Cycle 2 Days 1 and Cycle 3 Days 1: pre-infusion and at multiple time points (up to 24 hours) post-infusion (Cycle length=21 days)]
• Maximum observed concentration (Cmax) following administration of HG381 alone [Срок оценки: Cycle 1 Days 1, Cycle 2 Days 1 and Cycle 3 Days 1: pre-infusion and at multiple time points (up to 24 hours) post-infusion (Cycle length=21 days)]
• Area under the concentration-time curve (AUC) following administration of HG381 alone [Срок оценки: Cycle 1 Days 1, Cycle 2 Days 1 and Cycle 3 Days 1: pre-infusion and at multiple time points (up to 24 hours) post-infusion (Cycle length=21 days)]
• Apparent terminal phase half-life (t½) following administration of HG381 alone [Срок оценки: Cycle 1 Days 1, Cycle 2 Days 1 and Cycle 3 Days 1: pre-infusion and at multiple time points (up to 24 hours) post-infusion (Cycle length=21 days)]

Критерии участия

Критерии включения

• Capable of giving signed informed consent.
• Life expectancy of at least 3 months.
• Histological or cytological documentation of an advanced solid tumor，subjects with advanced/recurrent solid tumors, who have progressed on, be intolerant of, or ineligible for, all available therapies for which clinical benefit has been established.
• Measurable disease per RECIST version 1.1, there is at least one measurable lesion during the screening period.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
• Adequate organ function : Hematologic system: Hemoglobin ≥9 g/dL, Absolute neutrophil count \[ANC\] ≥1.5x10\^9/L, Platelets ≥100x10\^9/L, INR ≤ 1.5 and APTT ≤1.5 x ULN; Hepatic system: Total bilirubin ≤1.5 x ULN, ALT and AST ≤ 2.5 x ULN; Renal system: serum creatinine ≤1.5×ULN or creatinine clearance ≥50 mL/min (calculated by the Cockcroft-Gault formula); Cardiac system: left ventricular ejection fraction (LVEF) ≥50% ; QT interval (QTcF) ≤470 ms for women, and ≤450 ms for men; Endocrine system: Thyroid-stimulating hormone (TSH) is within the normal limits.
• Subjects with fertility must agree to take medically approved effective contraceptive measures during the entire trial period and at least 3 months after the last medication.

Критерии исключения

• Chemotherapy, radiotherapy, biological therapy, endocrine therapy, immunotherapy and other anticancer therapy within 4 weeks.
• Concurrent medical condition requiring the use of other systemic immunosuppressive treatment within 4 weeks before the first dose of study treatment.
• Receipt of any live vaccine within 4 weeks of the start of study treatment.
• Receipt of unmarketed clinical trial drugs or treatments within 4 weeks of the start of study treatment.
• Receipt of surgery or interventional treatment (excluding tumor biopsy, puncture, etc.) within 4 weeks of the start of study treatment.
• History or evidence of cardiovascular and cerebrovascular diseases risk.
• Subjects with uncontrolled diabetes.
• Symptomatic central nervous system (CNS) metastases or asymptomatic CNS metastases that have required steroids within 2 weeks prior to first dose of study treatment.
• Currently or in the past suffering from malignant tumors.
• Uncontrollable pleural effusion, pericardial effusion or ascites still need to be drained frequently after appropriate intervention.
• Active or suspected autoimmune disease.
• History of idiopathic pulmonary fibrosis, interstitial lung disease, or organizing pneumonia, or evidence of active, non-infectious pneumonitis.
• Toxicity from previous treatment including: Toxicity Grade ≥3 related to prior immunotherapy and that led to study treatment discontinuation; Toxicity related to prior treatment that has not resolved to Grade ≤ 1.
• Subjects who have acute bacterial, viral or fungal infections and require systemic anti-infective treatment.
• Positive test for syphilis antibodies or human immunodeficiency virus (HIV) antibodies.
• Subjects who are allergic to test drugs and excipients.
• Women who are pregnant or breastfeeding.
• Known drug or alcohol abuse.
• Patients with mental or neurological diseases.
• Prior allogeneic or autologous bone marrow transplantation or other solid organ transplantation.
• Subjects who have a history of serious systemic disease or any other reason are not suitable to participate in this trial as judged by the investigator.

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

Китай · 1 центр

• HitGen Inc. — Чэнду

Публикации

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Идентификаторы

NCT: NCT04998422 · HG381CN101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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