Clinical trial NCT06219356: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Non-Hodgkin Lymphoma
Lead sponsor: Hangzhou GluBio Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-01-23
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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).


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.

Primary outcomes:
measure: Dose-limiting Toxicity (DLT)
timeFrame: Up to 35 days after first dose of study treatment in Phase 1a
measure: Maximum Tolerated Dose (MTD)
timeFrame: Up to 2 years (each cycle is 28 days)
measure: Recommended Expansion Doses (RED)
timeFrame: Up to 2 years (each cycle is 28 days)
measure: Incidence, Relatedness, Seriousness and Severity of Adverse Events (AEs)
timeFrame: Up to 2 years
measure: Recommended Phase 2 Dose (RP2D)
timeFrame: Up to 2 years
measure: Objective Response Rate (ORR)
timeFrame: Up to 2 years
measure: Time to Response (TTR)
timeFrame: Up to 2 years
measure: Duration of Remission or Response (DOR)
timeFrame: Up to 2 years
measure: Progression-free Survival (PFS)
timeFrame: Up to 2 years
measure: Overall Survival (OS)
timeFrame: Up to 2 years
Secondary outcomes:
measure: GLB-002 and GLB-A062-A (R-enantiomers of GLB-002) Pharmacokinetics after Single Administration-AUC0-last
timeFrame: Up to 48 hours after single administration
measure: GLB-002 and GLB-A062-A Pharmacokinetics after Single Administration-AUC0-24
timeFrame: Up to 48 hours after single administration
measure: GLB-002 and GLB-A062-A Pharmacokinetics after Single Administration-AUC0-inf
timeFrame: Up to 48 hours after single administration
measure: GLB-002 and GLB-A062-A Pharmacokinetics after Single Administration-Cmax
timeFrame: Up to 48 hours after single administration
measure: GLB-002 and GLB-A062-A Pharmacokinetics after Single Administration-Tmax
timeFrame: Up to 48 hours after single administration
measure: GLB-002 and GLB-A062-A Pharmacokinetics after Single Administration-T1/2
timeFrame: Up to 48 hours after single administration
measure: GLB-002 and GLB-A062-A Pharmacokinetics after Single Administration-Vz/F
timeFrame: Up to 48 hours after single administration
measure: GLB-002 and GLB-A062-A Pharmacokinetics after Single Administration-CL/F
timeFrame: Up to 48 hours after single administration
measure: GLB-002 and GLB-A062-A Pharmacokinetics after Single Administration-λz
timeFrame: Up to 48 hours after single administration
measure: GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-Tmax,SS
timeFrame: Up to 2 years
measure: GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-Cav,SS
timeFrame: Up to 2 years
measure: GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-Cmax,SS
timeFrame: Up to 2 years
measure: GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-Cmin,SS
timeFrame: Up to 2 years
measure: GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-AUC0-tau
timeFrame: Up to 2 years
measure: GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-λz
timeFrame: Up to 2 years
measure: GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-Vz/F
timeFrame: Up to 2 years
measure: GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-CLSS/F
timeFrame: Up to 2 years
measure: GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-T1/2
timeFrame: Up to 2 years
measure: GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-Rac [AUC]
timeFrame: Up to 2 years
measure: GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-Rac [Cmax]
timeFrame: Up to 2 years
measure: GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-DF
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Nanchang
country: China
facility: Jiangxi Cancer Hospital
state: Jiangxi
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Tianjin
country: China
facility: Tianjing Medical University Cancer Institute and Hospital
state: Tianjin
city: Hangzhou
country: China
facility: The First Affilicated Hospital, Zhejiang University School of Medicine
state: Zhejiang
Study officials:
affiliation: Hangzhou GluBio Pharmaceutical Co., Ltd.
name: Gang Lu, Ph.D.
role: STUDY_DIRECTOR
References: