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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose Escalation of GLB-002 in Participants with R/R NHL-Phase 1a | Experimental | Part 1a (Dose Escalation) of the study will enroll R/R NHL participants and will evaluate the safety, tolerability, PK, PD and preliminary efficacy of GLB-002 administered orally, and determine the maximum tolerated dose (MTD) and/or recommended expansion doses (RED) in R/R NHL patients who are eligible for dose limiting toxicity (DLT) evaluation. |
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| Dose Expansion of GLB-002 in Participants with R/R FL (Grade 1, 2, 3a)-Phase 1b Cohort 1 | Experimental | Part 1b (Dose Expansion) Cohort 1 will confirm tolerability of the selected doses and schedules and evaluate whether efficacy is in a range that warrants further clinical development for R/R Follicular Lymphoma (Grade 1、2、3a). |
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| Dose Expansion of GLB-002 in Participants with R/R DLBCL and FL (Grade 3b)-Phase 1b Cohort 2 | Experimental | Confirm tolerability of the selected doses and schedules and evaluate whether efficacy is in a range that warrants further clinical development for R/R Diffuse Large B-cell Lymphoma and R/R Follicular Lymphoma (Grade 3b). |
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| Dose Expansion of GLB-002 in Participants with other R/R NHL-Phase 1b Cohort 3 | Experimental | Part 1b (Dose Expansion) Cohort 3 will confirm tolerability of the selected doses and schedules and evaluate whether efficacy is in a range that warrants further clinical development for other R/R NHL, including, but not limited to Mantle-cell Lymphoma (MCL), Marginal Zone Lymphoma (MZL), Small Lymphocytic Lymphoma (SLL) /Chronic Lymphocytic Leukemia (CLL) and Peripheral T-cell Lymphoma (PTCL). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GLB-002 | Drug | Administered orally according to the assigned treatment schedule. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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. | 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. | 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. | Up to 2 years |
| Objective Response Rate (ORR) |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Up to 48 hours after single administration |
| GLB-002 and GLB-A062-A Pharmacokinetics after Single Administration-AUC0-24 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jing Liu, MD | Contact | 86-18616699599 | Jing.Liu@glubiotx.com |
| Name | Affiliation | Role |
|---|---|---|
| Gang Lu, Ph.D. | Hangzhou GluBio Pharmaceutical Co., Ltd. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing Cancer Hospital | Recruiting | Beijing | Beijing Municipality | 100142 | China |
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| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
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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). |
| 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. | 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. | 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. | 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. | Up to 2 years |
Area under the concentration-time curve from 0 to 24 hours |
| 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 | Up to 48 hours after single administration |
| GLB-002 and GLB-A062-A Pharmacokinetics after Single Administration-Cmax | Maximum plasma concentration | Up to 48 hours after single administration |
| GLB-002 and GLB-A062-A Pharmacokinetics after Single Administration-Tmax | The time to reach maximum concentration | Up to 48 hours after single administration |
| GLB-002 and GLB-A062-A Pharmacokinetics after Single Administration-T1/2 | Terminal half-life | Up to 48 hours after single administration |
| GLB-002 and GLB-A062-A Pharmacokinetics after Single Administration-Vz/F | Apparent volume of distribution | 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 | Up to 48 hours after single administration |
| GLB-002 and GLB-A062-A Pharmacokinetics after Single Administration-λz | Terminal rate constant | 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 | Up to 2 years |
| GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-Cav,SS | Average plasma concentration at steady state | Up to 2 years |
| GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-Cmax,SS | Maximum plasma concentration at steady state | Up to 2 years |
| GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-Cmin,SS | Minimum plasma concentration at steady state | 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 | Up to 2 years |
| GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-λz | Terminal rate constant | Up to 2 years |
| GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-Vz/F | Apparent volume of distribution | Up to 2 years |
| GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-CLSS/F | Apparent clearance at steady state | Up to 2 years |
| GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-T1/2 | Terminal half-life | 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 | Up to 2 years |
| GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-Rac [Cmax] | Accumulation index in maximum plasma concentration | Up to 2 years |
| GLB-002 and GLB-A062-A Pharmacokinetics after Multiple Administration-DF | Degree of fluctuation index | Up to 2 years |
| Peking University Third Hospital | Recruiting | Beijing | Beijing Municipality | 100191 | China |
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| The First Affiliated Hospital of Xiamen University | Recruiting | Xiamen | Fujian | 361003 | China |
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| Sun Yat-Sen University Cancer Center | Recruiting | Guangzhou | Guangdong | 510060 | China |
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| Henan Cancer Hospital | Recruiting | Zhengzhou | Henan | 450003 | China |
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| Union Hospital, Tongji Medical College, Huazhong University of Science and Technology | Recruiting | Wuhan | Hubei | 430023 | China |
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| Hunan Cancer Hospital | Recruiting | Changsha | Hunan | 410000 | China |
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| Jiangxi Cancer Hospital | Recruiting | Nanchang | Jiangxi | 330029 | China |
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| Shengjing Hospital of China Medical University | Recruiting | Shenyang | Liaoning | 110004 | China |
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| Fudan University Shanghai Cancer Center | Recruiting | Shanghai | Shanghai Municipality | 200032 | China |
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| Shanxi Cancer hospital | Recruiting | Taiyuan | Shanxi | 030000 | China |
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| Tianjing Medical University Cancer Institute and Hospital | Recruiting | Tianjin | Tianjin Municipality | 300020 | China |
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| The First Affilicated Hospital, Zhejiang University School of Medicine | Recruiting | Hangzhou | Zhejiang | 310003 | China |
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| D008206 |
| Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |