A First-in-human, Phase 1, Dose Escalation and Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of GLB-001 in Patients With Relapsed or Refractory Acute Myeloid Leukemia or Relapsed or Refractory Higher-risk Myelodysplastic Syndromes
Study GLB-001-01 is a first-in-human (FIH), Phase 1, open-label, dose escalation and expansion clinical study of GLB-001 in participants with relapsed or refractory acute myeloid leukemia (R/R AML) or in participants with relapsed or refractory higher-risk myelodysplastic syndromes (R/R HR-MDS). The dose escalation part (Phase 1a) of the study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of GLB-001 administered orally. Approximately 24 participants (up to 42 participants) may be enrolled in Phase 1a of the study. The dose expansion part (Phase 1b) will be followed to understand 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. Up to 24 participants (12 participants per dose level) may be enrolled in Phase 1b of the study.
• Participants is ≥ 18 years of age at the time of signing the Informed Consent Form (ICF).
• Participants must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
• Participants are willing and able to adhere to the study visit schedule and other protocol requirements.
• Participants with histologically or cytologically confirmed AML including de novo AML or secondary AML transformed from MDS according to 2022 World Health Organization (WHO) criteria classification, or with histologically or cytologically confirmed HR-MDS.
• R/R AML and R/R HR-MDS who have failed or are ineligible for all available therapies which may provide clinical benefit.
• Participants must have the following screening laboratory values:
‣ Total white blood cell count (WBC) \< 25 x 10\^9/L prior to the first dose of the study drug.
⁃ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × upper limit of normal (ULN), unless considered due to extensive leukemic liver involvement, in which case AST and ALT can be ≤ 5.0 x ULN.
⁃ Serum total bilirubin ≤ 1.5 x ULN, unless considered due to Gilbert's syndrome, in which case serum total bilirubin \< 3 x ULN.
⁃ Estimated serum creatinine clearance of ≥ 60 mL/min using the Cockcroft-Gault equation. Measured creatinine clearance from a 24-hour urine collection is acceptable if clinically indicated.
⁃ International normalized ratio (INR) ≤ 1.5 x ULN and active partial thromboplastin time (aPTT) ≤ 1.5 x ULN.
• Life expectancy ≥ 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.
• Female Participants of child-bearing potential must have a negative serum or urine pregnancy test at screening and at pre-dose on Cycle 1 Day 1 (C1D1).