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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
110
Administered orally according to the assigned treatment schedule.
Beijing Cancer Hospital
Beijing, Beijing Municipality, China
RECRUITINGPeking University Third Hospital
Beijing, Beijing Municipality, China
Dose-limiting Toxicity (DLT)
DLT is defined as the treatment emergent adverse events (TEAEs) meeting protocol specified DLT criteria and occurring within the DLT assessment period, except those that are clearly and incontrovertibly due to extraneous causes including disease progression, pre-existing medical condition that has not worsened from baseline, or other causes that are clearly not due to study drug.
Time frame: Up to 35 days after first dose of study treatment in Phase 1a
Maximum Tolerated Dose (MTD)
MTD is defined as the highest dose level at which no more than 1 of 6 DLT-evaluable participants experienced a DLT.
Time frame: Up to 2 years (each cycle is 28 days)
Recommended Expansion Doses (RED)
RED will be decided by safety review committee (SRC) considering the data including safety, tolerability, PK, PD, and preliminary efficacy of GLB-002 in dose escalation. RED will be the dose level below MTD.
Time frame: Up to 2 years (each cycle is 28 days)
Incidence, Relatedness, Seriousness and Severity of Adverse Events (AEs)
AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. AE will be graded according to the National Cancer Institute Common Terminology Criteria for AE (NCI CTCAE) version 5.0.
Time frame: Up to 2 years
Recommended Phase 2 Dose (RP2D)
RP2D based on the totality of data across dosing cohorts in the dose escalation and expansion phases of the study including PK, PD, safety and efficacy outcomes.
Time frame: Up to 2 years
Objective Response Rate (ORR)
ORR is defined as the percent of participants whose best overall response is complete response (CR) or partial response (PR). CR and PR will be assessed by 2014 Lugano for NHL and/or 2018 International Working Group Criteria for Chronic Lymphocyte Leukemia (2018 IWCLL).
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The First Affiliated Hospital of Xiamen University
Xiamen, Fujian, China
RECRUITINGSun Yat-Sen University Cancer Center
Guangzhou, Guangdong, China
RECRUITINGHenan Cancer Hospital
Zhengzhou, Henan, China
RECRUITINGUnion Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, China
RECRUITINGHunan Cancer Hospital
Changsha, Hunan, China
RECRUITINGJiangxi Cancer Hospital
Nanchang, Jiangxi, China
RECRUITINGShengjing Hospital of China Medical University
Shenyang, Liaoning, China
RECRUITINGFudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, China
RECRUITING...and 3 more locations
Time frame: Up to 2 years
Time to Response (TTR)
For participants with objective response, TTR was defined as the time of participants from the first treatment administration to the first incidence of a confirmed CR or PR was reported. CR and PR will be assessed by 2014 Lugano for NHL and/or 2018 IWCLL.
Time frame: Up to 2 years
Duration of Remission or Response (DOR)
For participants with objective response, DOR is measured from the time of any of CR or PR are first met (whichever is first recorded) until the first date at which progressive disease or death from any cause is objectively documented assessment. CR and PR will be assessed by 2014 Lugano for NHL and/or 2018 IWCLL.
Time frame: Up to 2 years
Progression-free Survival (PFS)
PFS is defined as the time from the first dose of GLB-002 to the first occurrence of progressive disease (PD) or death from any cause. PD will be assessed by 2014 Lugano for NHL and/or 2018 IWCLL.
Time frame: Up to 2 years
Overall Survival (OS)
OS is defined as the time from the first dose of GLB-002 to death due to any cause.
Time frame: Up to 2 years
GLB-002 and GLB-A062-A (R-enantiomers of GLB-002) Pharmacokinetics after Single Administration-AUC0-last
Area under the concentration-time curve from zero to the last measurable concentration
Time frame: Up to 48 hours after single administration
GLB-002 and GLB-A062-A Pharmacokinetics after Single Administration-AUC0-24
Area under the concentration-time curve from 0 to 24 hours
Time frame: Up to 48 hours after single administration
GLB-002 and GLB-A062-A Pharmacokinetics after Single Administration-AUC0-inf
Area under the concentration-time curve from 0 to infinity
Time frame: Up to 48 hours after single administration
GLB-002 and GLB-A062-A Pharmacokinetics after Single Administration-Cmax
Maximum plasma concentration
Time frame: Up to 48 hours after single administration
GLB-002 and GLB-A062-A Pharmacokinetics after Single Administration-Tmax
The time to reach maximum concentration
Time frame: Up to 48 hours after single administration
GLB-002 and GLB-A062-A Pharmacokinetics after Single Administration-T1/2
Terminal half-life
Time frame: Up to 48 hours after single administration
GLB-002 and GLB-A062-A Pharmacokinetics after Single Administration-Vz/F
Apparent volume of distribution
Time frame: Up to 48 hours after single administration
GLB-002 and GLB-A062-A Pharmacokinetics after Single Administration-CL/F
Apparent total clearance of the drug from plasma after oral administration
Time frame: Up to 48 hours after single administration
GLB-002 and GLB-A062-A Pharmacokinetics after Single Administration-λz
Terminal rate constant
Time frame: Up to 48 hours after single administration
GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-Tmax,SS
Time of maximum concentration at steady state
Time frame: Up to 2 years
GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-Cav,SS
Average plasma concentration at steady state
Time frame: Up to 2 years
GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-Cmax,SS
Maximum plasma concentration at steady state
Time frame: Up to 2 years
GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-Cmin,SS
Minimum plasma concentration at steady state
Time frame: Up to 2 years
GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-AUC0-tau
Area under the concentration-time curve during the dosing interval
Time frame: Up to 2 years
GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-λz
Terminal rate constant
Time frame: Up to 2 years
GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-Vz/F
Apparent volume of distribution
Time frame: Up to 2 years
GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-CLSS/F
Apparent clearance at steady state
Time frame: Up to 2 years
GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-T1/2
Terminal half-life
Time frame: Up to 2 years
GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-Rac [AUC]
Accumulation index in area under the concentration-time curve
Time frame: Up to 2 years
GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-Rac [Cmax]
Accumulation index in maximum plasma concentration
Time frame: Up to 2 years
GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-DF
Degree of fluctuation index
Time frame: Up to 2 years