A Study of GLB-001 in Patients With Myeloid Malignancies

Official title

A Phase 1, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of GLB-001 in Patients With Myeloid Malignancies

Overview

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.

Interventions

• Drug GLB-001
  Administered orally according to the assigned treatment schedule

Primary outcome measures

• Dose-limiting Toxicity (DLT) [Time frame: Up to 28 days after first dose of study treatment in Phase 1a and Phase 1b]
• Maximum Tolerated Dose (MTD) [Time frame: Up to 1 year in Phase 1a and Phase 1b]
• Recommended Expansion Doses (RED) [Time frame: Up to 1 year in Phase 1a and Phase 1b]
• Incidence, Relatedness, Seriousness and Severity of Adverse Events (AEs) [Time frame: Up to 3 years in Phase 1a and Phase 1b]
• Recommended Phase 2 Dose (RP2D) [Time frame: Up to 1 year in Phase 1c]
• Response Assessment in Study Participants With PV [Time frame: Up to 3 year in Phase 1c]
• Response Assessment in Study Participants With ET [Time frame: Up to 1 year in Phase 1c]
• Response Assessment in Study Participants With MF [Time frame: Up to 1 year in Phase 1c]
• Response Assessment in Study Participants With LR-MDS [Time frame: Up to 1 year in Phase 1c]
• Response Assessment in Study Participants With HR-MDS [Time frame: Up to 1 year in Phase 1c]

Secondary outcome measures (12)

• GLB-001 and GLB-C183-A-2 (diastereoisomer of GLB-001) Pharmacokinetics after Single Administration - AUC0-last [Time frame: Up to 48 hours after single administration]
• GLB-001 and GLB-C183-A-2 Pharmacokinetics after Single Administration - AUC0-24 [Time frame: Up to 48 hours after single administration]
• GLB-001 and GLB-C183-A-2 Pharmacokinetics after Single Administration - AUC0-inf [Time frame: Up to 48 hours after single administration]
• GLB-001 and GLB-C183-A-2 Pharmacokinetics after Single Administration - Cmax [Time frame: Up to 48 hours after single administration]
• GLB-001 and GLB-C183-A-2 Pharmacokinetics after Single Administration - Tmax [Time frame: Up to 48 hours after single administration]
• GLB-001 and GLB-C183-A-2 Pharmacokinetics after Single Administration - T1/2 [Time frame: Up to 48 hours after single administration]
• GLB-001 and GLB-C183-A-2 Pharmacokinetics after Single Administration - Vz/F [Time frame: Up to 48 hours after single administration]
• GLB-001 and GLB-C183-A-2 Pharmacokinetics after Single Administration - CL/F [Time frame: Up to 48 hours after single administration]
• GLB-001 and GLB-C183-A-2 Pharmacokinetics after Single Administration - λz [Time frame: Up to 48 hours after single administration]
• GLB-001 and GLB-C183-A-2 Pharmacokinetics after Multiple Administration - Tmax,ss [Time frame: Up to 1 year]
• GLB-001 and GLB-C183-A-2 Pharmacokinetics after Multiple Administration - Cav,ss [Time frame: Up to 1 year]
• GLB-001 and GLB-C183-A-2 Pharmacokinetics after Multiple Administration - Cmax,ss [Time frame: Up to 1 year]

Eligibility 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 > 450 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 14 centers

• The First Affiliated Hospital of University of Science and Technology of China (Anhui Prov — Hefei
• China-Japan Friendship Hospital — Beijing
• The First Affiliated Hospital of Chongqing Medical University — Chongqing
• The First Hospital of Hebei Medical Universtiy — Shijiazhuang
• Henan Cancer Hospital — Zhengzhou
• Zhongnan Hospital of Wuhan University — Wuhan
• The First Affiliated Hospital of Soochow University — Suzhou
• The First Affiliated Hospital of Nanchang University — Nanchang
• … and 6 more centers

Identifiers

NCT: NCT06378437 · GLB-001-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗