A Study of GLB-002 in Patients With Relapsed or Refractory Non-Hodgkin Lymphomas

Официальное название

A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of GLB-002 in Patients With Relapsed or Refractory Non-Hodgkin Lymphomas (R/R NHL)

Обзор

Study GLB-002-01 is a first-in-human (FIH), phase 1, open-label, dose escalation and expansion clinical study, the purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of GLB-002 monotherapy in participants with relapsed or refractory Non-Hodgkin lymphomas (R/R NHL).

Вмешательства

• Препарат GLB-002
  Administered orally according to the assigned treatment schedule.

Первичные конечные точки

• Dose-limiting Toxicity (DLT) [Срок оценки: Up to 35 days after first dose of study treatment in Phase 1a]
• Maximum Tolerated Dose (MTD) [Срок оценки: Up to 2 years (each cycle is 28 days)]
• Recommended Expansion Doses (RED) [Срок оценки: Up to 2 years (each cycle is 28 days)]
• Incidence, Relatedness, Seriousness and Severity of Adverse Events (AEs) [Срок оценки: Up to 2 years]
• Recommended Phase 2 Dose (RP2D) [Срок оценки: Up to 2 years]
• Objective Response Rate (ORR) [Срок оценки: Up to 2 years]
• Time to Response (TTR) [Срок оценки: Up to 2 years]
• Duration of Remission or Response (DOR) [Срок оценки: Up to 2 years]
• Progression-free Survival (PFS) [Срок оценки: Up to 2 years]
• Overall Survival (OS) [Срок оценки: Up to 2 years]

Вторичные конечные точки (12)

• GLB-002 and GLB-A062-A (R-enantiomers of GLB-002) Pharmacokinetics after Single Administration-AUC0-last [Срок оценки: Up to 48 hours after single administration]
• GLB-002 and GLB-A062-A Pharmacokinetics after Single Administration-AUC0-24 [Срок оценки: Up to 48 hours after single administration]
• GLB-002 and GLB-A062-A Pharmacokinetics after Single Administration-AUC0-inf [Срок оценки: Up to 48 hours after single administration]
• GLB-002 and GLB-A062-A Pharmacokinetics after Single Administration-Cmax [Срок оценки: Up to 48 hours after single administration]
• GLB-002 and GLB-A062-A Pharmacokinetics after Single Administration-Tmax [Срок оценки: Up to 48 hours after single administration]
• GLB-002 and GLB-A062-A Pharmacokinetics after Single Administration-T1/2 [Срок оценки: Up to 48 hours after single administration]
• GLB-002 and GLB-A062-A Pharmacokinetics after Single Administration-Vz/F [Срок оценки: Up to 48 hours after single administration]
• GLB-002 and GLB-A062-A Pharmacokinetics after Single Administration-CL/F [Срок оценки: Up to 48 hours after single administration]
• GLB-002 and GLB-A062-A Pharmacokinetics after Single Administration-λz [Срок оценки: Up to 48 hours after single administration]
• GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-Tmax,SS [Срок оценки: Up to 2 years]
• GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-Cav,SS [Срок оценки: Up to 2 years]
• GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-Cmax,SS [Срок оценки: Up to 2 years]

Критерии участия

Критерии включения

• Participants must understand and voluntarily sign a written informed consent form (ICF) prior to any study-related assessments/procedures being performed.
• Participants is ≥18 years of age at the time of signing the ICF.
• Participants with histopathologically or immunohistochemically confirmed NHL according to 2016 World Health Organization (WHO) haematolymphoid tumors criteria classification (CLL/SLL diagnosis according to 2018 IWCLL) who have failed standard of care therapy or lack an effective treatment regimen.
• Participants in Phase Ib screening period with measurable lesion, but no measurable nodal lesion limit for participants in Phase Ia.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2.
• Life expectancy > 3 months.
• Good performance of major organs, including hematology, liver and kidney function, and coagulation. etc.
• Participants are willing and able to adhere to the study visit schedule and other protocol requirements.

Критерии исключения

• Receipt of anticancer medications/therapies such as chemotherapy, targeted therapy, immunotherapy, biologic therapy, or herbal agent ≤ 28 days or 5 half-lives, whichever is shorter, prior to the first dose of GLB-002; or chimeric antigen receptor T cell therapy (CAR-T) within 3 months prior to the first dose of GLB-002.
• Currently enrolled in any other investigational drug study or participation within the last 28 days or 5 half-lives, whichever is shorter, prior to the first dose of GLB-002 (exception of participants who participated in only one investigational drug study with overall survival follow-up).
• Participants with unresolved clinically significant toxicities of > Grade 1 AE or not be recovered to baseline value from prior anticancer therapies with exception of alopecia or hyperpigmentation of the skin.
• Participants who are scheduled to receive other anticancer therapies or other investigational drugs during the study period.
• Participants with active acute or chronic graft versus host disease (GVHD) requiring systemic immunosuppressive therapy, or participants requiring treatment with systemic corticosteroids (>10 mg/day prednisone or equivalent) or other immunosuppressive drugs within the last 7 days prior to the first dose of GLB-002 or during the study period.
• Receipt of Autologous Stem Cell Transplantation (ASCT) within the last 3 months, or allogeneic hematopoietic stem cell transplantation (allo-HSCT) within the last 6 months prior to the first dose of GLB-002.
• Participants with known active leukemic involvement in central nervous system (CNS).
• Participants with peripheral neuropathy ≥ Grade 2 (Graded according to CTCAE version 5.0).
• History of, or current active cancer other malignancy for the past 5 years, with the exception of curatively resected cancer in situ, including cervical carcinoma in situ, basal cell carcinoma of the skin, or prostate cancer in situ, etc
• QT interval interval >470 milliseconds (ms) using electrocardiographic (ECG) at Screening.
• Participants has impaired cardiac function or clinically significant cardiac disease at current or within last 6 months.
• Participants with known active infection of hepatitis B virus (HBV) or hepatitis C virus C (HCV).
• Participants with known human immunodeficiency virus (HIV) infection.
• Participants with known life-threatening or clinical significant uncontrolled active systemic infections unrelated to malignant hematologic diseases
• Participants with a condition that may affects the absorption, distribution, metabolism and excretion of GLB-002.
• Medications or supplements that are known to be strong and moderate inhibitors or inducers of cytochrome P-450 isozyme (CYP)3A4/5 and/or P-glycoprotein (P-gp) within 7 days or 5 half-lives prior to the first dose of GLB-002, whichever is shorter.
• Participants who have undergone major surgery within 28 days prior to the first dose of the GLB-002.
• Pregnant or lactating women.
• Participants who have cognitive impairment due to any psychiatric or neurological condition, including epilepsy and dementia, may limit their understanding, performance, and study compliance with the ICF.
• Participants,in the opinion of the Investigator, who are unsuitable to participate in the study.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 13 центров

• Beijing Cancer Hospital — Пекин
• Peking University Third Hospital — Пекин
• The First Affiliated Hospital of Xiamen University — Xiamen
• Sun Yat-Sen University Cancer Center — Гуанчжоу
• Henan Cancer Hospital — Чжэнчжоу
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Ухань
• Hunan Cancer Hospital — Чанша
• Jiangxi Cancer Hospital — Nanchang
• … и ещё 5 центров

Идентификаторы

NCT: NCT06219356 · GLB-002-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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