A Study of GLB-001 in Patients With Myeloid Malignancies

Study Purpose

Study GLB-001-02 is a phase 1, open-label clinical study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of GLB-001 in study participants with relapsed or refractory or intolerant myeloid malignancies including polycythemia vera (PV), essential thrombocythemia (ET), myelofibrosis (MF), lower-risk myelodysplastic syndrome (LR-MDS), higher-risk myelodysplastic syndromes (HR-MDS), and acute myeloid leukemia (AML). This study consists of 3 parts, dose escalation (Phase 1a), dose exploration (Phase 1b) and dose expansion (Phase 1c). Dose escalation (Phase 1a) and dose exploration (Phase 1b) will evaluate the safety, tolerability, PK, PD and preliminary efficacy of GLB-001, administered orally, in study participants with PV/ET, or study participants with MF/LR-MDS/HR-MDS/AML, respectively. Dose expansion (Phase 1c) will be followed to determine the relationships among dose, exposure, toxicity, tolerability and clinical activity, to identify minimally active dose, and to select the recommended dose(s) for phase 2 study. Approximately 108 study participants may be enrolled in the study.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- Study participants must understand and voluntarily sign a written informed consent form (ICF) prior to any study-related assessments/procedures being performed.

- Study participants is ≥18 years of age at the time of signing the ICF.

- Study participants with confirmed diagnosis of relapsed or refractory or intolerant myeloid malignancies including PV, ET, primary myelofibrosis (PMF), MDS and AML according to 2022 World Health Organization (WHO) criteria classification, and post-polycythemia vera myelofibrosis (post-PV MF) and post-essential thrombocythemia myelofibrosis (post-ET MF) according to the 2013 IWG-MRT criteria.

- 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.

- Study participants are willing and able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

- Study participants with acute promyelocytic leukemia (APL).

- Receipt of following anticancer medications/therapies prior to the first dose of GLB-001: (1) study participants with PV or ET who received treatment with hydroxyurea within 2 days prior to the first dose, or any other treatment for PV or ET within 7 days prior to first dose of GLB-001, (2) study participants with MF who received any type of treatment for MF within 14 days prior to the first dose, such as chemotherapy, immunotherapy, radiotherapy and erythropoietin, androgens, thrombopoietin or granulocyte colony-stimulating factor, (3) study participants with LR-MDS who received any type of treatment for MDS within 14 days prior to the first dose, (4) study participants with HR-MDS or AML who received chimeric antigen receptor T cell therapy (CAR-T) or other biologic therapy within 28 days prior to the first dose of GLB-001, or received any other anticancer therapies within 14 days prior to the first dose of GLB-001.

- Receipt of any other investigational drug study within 28 days or 5 half-lives of that study drug before the first dose of GLB-001.

- Study participants with unresolved clinically significant non-hematologic toxicities that were ≥ Grade 1 or failed to recover to baseline levels following prior anticancer therapies (with the exception of alopecia or skin hyperpigmentation).

- Study participants who are scheduled to receive other anticancer therapies or other investigational drugs during the study period.

- Study participants with active acute or chronic graft versus host disease (GVHD) requiring systemic immunosuppressive therapy.

- Receipt of autologous stem cell transplantation (ASCT) within the last 3 months prior to the first dose of GLB-001, or allogeneic hematopoietic stem cell transplantation (allo-HSCT) within the last 6 months prior to the first dose of GLB-001.

- Study participants with known active involvement in central nervous system (CNS).

- Study participants with peripheral neuropathy ≥ Grade 2 (Graded according to CTCAE version 5.0).

- Study participants have a history of known malignancy other than the inclusion diagnosis 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.

- Study participants have impaired cardiac function or clinically significant cardiac disease at current or within last 6 months.

- Study participants with known active infection of hepatitis B virus (HBV) or hepatitis C virus C (HCV).

- Study participants with known human immunodeficiency virus (HIV) infection.

- Study participants with known life-threatening or clinical significant uncontrolled active systemic infections unrelated to malignant hematologic diseases.

- Study participants with a state condition that may alter affects the absorption, distribution, metabolism and excretion of GLB-001 after judgment of the investigator.

- Medications or supplements that are known to be strong and moderate inhibitors or inducers of cytochrome P-450 isozyme 3A (CYP3A) and/or P-glycoprotein (P-gp), or strong inhibitors or inducers of CYP450 isozyme 2C8 (CYP2C8) within 7 days or 5 half-lives prior to the first dose of GLB-001, whichever is shorter prior to the first dose of GLB-001.

- Study participants who have undergone major surgery within 28 days prior to the first dose of the GLB-001, or unability to recover from effects of surgery.

- Pregnant or lactating women.

- Study 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.

- Study participants, in the opinion of the Investigator, who are unsuitable to participate in the study.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06378437
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 1
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Hangzhou GluBio Pharmaceutical Co., Ltd.
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Gang Lu, Ph.D.
Principal Investigator Affiliation	Hangzhou GluBio Pharmaceutical Co., Ltd.
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	China
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Polycythemia Vera, Essential Thrombocythemia, Myelofibrosis, Myelodysplastic Syndromes, Acute Myeloid Leukemia, Myeloid Malignancy

Arms & Interventions

Arms

Experimental: Dose Escalation of GLB-001 in Study Participants with PV and ET-Phase 1a

Phase 1a (Dose Escalation) will evaluate the safety and tolerability of GLB-001 in PV and ET study participants. A standard 3+3 dose-escalation design will be applied to evaluate a set of dose levels to determine and the maximum tolerated dose (MTD) and/or recommended expansion doses (RED) in PV and ET study participants who are eligible for dose limiting toxicity (DLT) evaluation.

Experimental: Dose Exploration of GLB-001 in Study Participants with MF, LR-MDS, AML and HR-MDS-Phase 1b

Phase Ib 1b (Dose Exploration) will utilize a standard 3+3 dose-escalation design to evaluate the safety and tolerability of GLB-001 in MF, LR-MDS, HR-MDS and AML study participants. The starting dose will be selected within the range of tolerated dose levels determined in Phase 1a (Dose escalation).

Experimental: Dose Expansion of GLB-001 in Study Participants with PV, ET, MF, LR-MDS, AML and HR-MDS-Phase 1c

Phase 1c (Dose Expansion) will be conducted to further determine the tolerability, efficacy and the recommended phase 2 dose (RP2D) of GLB-001 in study participants with relapsed or refractory or intolerant myeloid malignancies including PV, ET, MF, LR-MDS, HR-MDS and AML.

Interventions

Drug: - GLB-001

Administered orally according to the assigned treatment schedule

Contact a Trial Team

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