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
Summary
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.
Detailed description
A standard 3+3 dose-escalation design will be applied to evaluate a set of several dose levels to determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) of GLB-001 in R/R AML or R/R HR-MDS patients who are eligible for DLT evaluation. The actual dose-escalation magnitude or dosing frequency may be adjusted based on the available PK and safety data in human. After the MTD or MAD of GLB-001 is defined in Phase 1a, 1 or 2 dose levels will be selected for expansion per safety review committee (SRC) recommendation, approximately 12 patients will be enrolled per dose level. Recommended phase 2 dose (RP2D) will be selected based on the results of PK, PD, safety and efficacy in the dose escalation and expansion study.
Arms & interventions
- DrugGLB-001
Administered orally according to the assigned treatment schedule
Outcome measures
Primary
Dose-limiting Toxicity (DLT)
Dose-limiting toxicity is defined as the treatment emergent adverse events (TEAEs) meeting protocol specified DLT criteria and occurring within the DLT assessment period.
Time frame: Up to 28 days after first dose of study treatment in Phase 1a
Maximum Tolerated Dose (MTD)/Maximum Administered Dose (MAD)
Maximum tolerated dose is defined as the highest dose level at which no more than 1 of 6 DLT-evaluable participants experienced a DLT. If MTD is not established at the end of dose escalation phase, the maximum safety dose will be defined as Maximum administered dose.
Time frame: Up to 2 years
Incidence of Adverse Events (AEs)
Adverse Events will be graded according to the National Cancer Institute Common Terminology Criteria for AE (NCI CTCAE) version 5.0.
Time frame: Up to 2 years
Recommended Phase 2 Dose (RP2D)
Recommended phase 2 dose 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.
Time frame: Up to 2 years
Secondary
GLB-001 Pharmacokinetics-AUC0-last
Time frame: Up to 2 years
GLB-001 Pharmacokinetics-AUC0-24
Time frame: Up to 2 years
GLB-001 Pharmacokinetics-AUC0-∞
Time frame: Up to 2 years
GLB-001 Pharmacokinetics-Cmax
Time frame: Up to 2 years
GLB-001 Pharmacokinetics-Tmax
Time frame: Up to 2 years
GLB-001 Pharmacokinetics-T1/2
Time frame: Up to 2 years
GLB-001 Pharmacokinetics-Vd/F
Time frame: Up to 2 years
GLB-001 Pharmacokinetics-LI
Time frame: Up to 2 years
GLB-001 Pharmacokinetics-CL/F
Time frame: Up to 2 years
GLB-C183-A-2R (Isomer of GLB-001) Pharmacokinetics-AUC0-last
Time frame: Up to 2 years
GLB-C183-A-2R Pharmacokinetics-AUC0-24
Time frame: Up to 2 years
GLB-C183-A-2R Pharmacokinetics-AUC0-∞
Time frame: Up to 2 years
GLB-C183-A-2R Pharmacokinetics-Cmax
Time frame: Up to 2 years
GLB-C183-A-2R Pharmacokinetics-Tmax
Time frame: Up to 2 years
GLB-C183-A-2R Pharmacokinetics-T1/2
Time frame: Up to 2 years
GLB-C183-A-2R Pharmacokinetics-Vd/F
Time frame: Up to 2 years
GLB-C183-A-2R Pharmacokinetics-LI
Time frame: Up to 2 years
GLB-C183-A-2R Pharmacokinetics-CL/F
Time frame: Up to 2 years
Complete Remission Without Minimal Residual Disease (CRMRD-) Rate in Participants with Acute Myeloid Leukemia (AML)
Time frame: Up to 2 years
Complete Remission (CR) Rate in Participants with AML
Time frame: Up to 2 years
CR with Incomplete Hematologic Recovery (CRi) Rate in Participants with AML
Time frame: Up to 2 years
CR with Partial Hematological Recovery (CRh) Rate in Participants with AML
Time frame: Up to 2 years
Morphologic Leukemia-free State (MLFS) Rate in Participants with AML
Time frame: Up to 2 years
Partial Remission (PR) Rate in Participants with AML
Time frame: Up to 2 years
Duration of Remission or Response (DOR) in Participants with AML
Time frame: Up to 2 years
Time to Remission or Response (TOR) in Participants with AML
Time frame: Up to 2 years
Stable Disease (SD) Rate in Participants with AML
Time frame: Up to 2 years
CR Rate in Participants with Higher Risk Myelodysplastic Syndromes (HR-MDS)
Time frame: Up to 2 years
PR Rate in Participants with HR-MDS
Time frame: Up to 2 years
SD Rate in Participants with HR-MDS
Time frame: Up to 2 years
DOR in Participants with HR-MDS
Time frame: Up to 2 years
TOR in Participants with HR-MDS
Time frame: Up to 2 years
Progression-free Survival (PFS) in Participants with AML or HR-MDS
Time frame: Up to 2 years
Overall Survival (OS) in Participants with AML or HR-MDS
Time frame: Up to 2 years
Eligibility criteria
Study locations (8)
City of Hope Medical Center
Duarte, California, 91010
University of California Irvine
Irvine, California, 92697
University of Kansas Medical Center Research Institute, Inc.
Kansas City, Kansas, 66160
Alliance for Multispecialty Research, LLC
Merriam, Kansas, 66204
Roswell Park Comprehensive Cancer Center
Buffalo, New York, 14263
Memorial Sloan Kettering Cancer Center-David H. Koch Center
New York, New York, 10021
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
University of Texas M. D. Anderson Cancer Center
Houston, Texas, 77030