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

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 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 Overview

• Status: Recruiting
• Conditions: Non-Hodgkin Lymphoma
• Intervention / Treatment: Drug: GLB-002

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jing Liu, MD; Phone Number: 86-18616699599; Email: Jing.Liu@glubiotx.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Beijing Cancer Hospital
      • Contact: Yuqing Song, MD; Phone Number: 86-010-88121122; Email: songyuqin622@163.com
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Zhiming Li, MD; Phone Number: 86-020-87343088; Email: lizhm@sysucc.org.cn
  • Henan
    • Zhengzhou, Henan, China, 450003
      • Recruiting
      • Henan Cancer Hospital
      • Contact: Keshu Zhou, MD; Phone Number: 86-0371-65587320; Email: drzhouks77@163.com
  • Jiangxi
    • Nanchang, Jiangxi, China, 330029
      • Recruiting
      • Jiangxi Cancer Hospital
      • Contact: Yuerong Shuang, MD; Phone Number: 86-0791-88315120; Email: shuangyr63@163.com
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Not yet recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Jian Zhang, MD; Phone Number: 86-021-64175590; Email: syner2000@163.com
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Recruiting
      • Tianjing Medical University Cancer Institute and Hospital
      • Contact: Lihua Qiu, MD; Phone Number: 86-022-23109106; Email: JZXQLH@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 (except corticosteroids at a dose equivalent to 12 mg or less of prednisone per day).
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation of GLB-002 in Participants with R/R NHL-Phase 1a; 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.	Drug: GLB-002; Administered orally according to the assigned treatment schedule.; Other Names: GLB-A062-B
Experimental: Dose Expansion of GLB-002 in Participants with R/R FL (Grade 1, 2, 3a)-Phase 1b Cohort 1; 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).	Drug: GLB-002; Administered orally according to the assigned treatment schedule.; Other Names: GLB-A062-B
Experimental: Dose Expansion of GLB-002 in Participants with R/R DLBCL and FL (Grade 3b)-Phase 1b Cohort 2; 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).	Drug: GLB-002; Administered orally according to the assigned treatment schedule.; Other Names: GLB-A062-B
Experimental: Dose Expansion of GLB-002 in Participants with other R/R NHL-Phase 1b Cohort 3; 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).	Drug: GLB-002; Administered orally according to the assigned treatment schedule.; Other Names: GLB-A062-B

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)	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

Secondary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Hangzhou GluBio Pharmaceutical Co., Ltd.
• Investigators: Study Director: Gang Lu, Ph.D., Hangzhou GluBio Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2024
• Primary Completion (Estimated): January 31, 2026
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: December 22, 2023
• First Submitted That Met QC Criteria: January 12, 2024
• First Posted (Actual): January 23, 2024

Study Record Updates

• Last Update Posted (Actual): April 26, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: GLB-002-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No