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.
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.
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).
Sequential
GLB-001
DrugAdministered orally according to the assigned treatment schedule
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.
Maximum Tolerated Dose (MTD)
MTD is defined as the highest dose level at which no more than 1 of 6 DLT-evaluable study participants experienced a DLT.
Recommended Expansion Doses (RED)
RED will be determined by the safety review committee (SRC) according to the safety, tolerability, PK, PD, and preliminary efficacy of GLB-001 in dose escalation phase and dose exploration phase.
Incidence, Relatedness, Seriousness and Severity of Adverse Events (AEs)
AE is any untoward medical occurrence in a study 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.
GLB-001 and GLB-C183-A-2 (diastereoisomer of GLB-001) Pharmacokinetics after Single Administration - AUC0-last
Area under the concentration-time curve from zero to the last measurable concentration.
GLB-001 and GLB-C183-A-2 Pharmacokinetics after Single Administration - AUC0-24
Area under the concentration-time curve from 0 to 24 hours.
GLB-001 and GLB-C183-A-2 Pharmacokinetics after Single Administration - AUC0-inf
Area under the concentration-time curve from 0 to infinity.
GLB-001 and GLB-C183-A-2 Pharmacokinetics after Single Administration - Cmax
Maximum plasma concentration.
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