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

Official title

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)

Overview

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).

Interventions

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

Primary outcome measures

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

Secondary outcome measures (12)

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

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 13 centers

• Beijing Cancer Hospital — Beijing
• Peking University Third Hospital — Beijing
• The First Affiliated Hospital of Xiamen University — Xiamen
• Sun Yat-Sen University Cancer Center — Guangzhou
• Henan Cancer Hospital — Zhengzhou
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan
• Hunan Cancer Hospital — Changsha
• Jiangxi Cancer Hospital — Nanchang
• … and 5 more centers

Identifiers

NCT: NCT06219356 · GLB-002-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗