This is a Phase 1a/1b, open-label, dose escalation and expansion study to evaluate the safety, tolerability, PK, pharmacodynamics, and preliminary efficacy of GNTbm-38 in adult patients with advanced solid tumors and R/R PTCL.
This study aims to investigate the maximum tolerated dose, safety, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of GNTbm-38. Phase 1a is the dose escalation phase to firstly determine the MTD of patients with solid tumor. Once MTD for solid tumor patients has been established, the next lower dose of this MTD will serve as an initial dose to determine the MTD for patients with R/R PTCL. Phase 1b is the dose expansion phase in which optimal design is utilized to evaluate the safety, tolerability, and efficacy of GNTbm-38 in R/R PTCL patients.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
70
Phase 1a is the dose escalation phase to firstly determine the MTD of patients with solid tumor. Once MTD for solid tumor patients has been established, the next lower dose of this MTD will serve as an initial dose to determine the MTD for patients with R/R PTCL. Phase 1b is the dose expansion phase to evaluate the safety, tolerability, and efficacy of GNTbm-38 in R/R PTCL patients.
Phase 1a: The MTD and DLT of GNTbm-38
The primary endpoint of the Phase 1a portion of the study was the incidence and severity of dose-limiting toxicities (DLTs) of GNTbm-38 administered orally once daily during the first cycle of evaluation (each cycle is 28 days). The efficacy assessments will be define by RECIST v1.1.
Time frame: At the end of Cycle 1 (each cycle is 28 days)
Phase Ia: To define the safety and tolerability
To evaluate the efficacy of GNTbm-38 via analysis of anti-tumor activity in adult patients with Relapsed or refractory peripheral T-cell lymphoma (R/R PTCL). The efficacy assessments will be define by 2014 Lugano classification.
Time frame: At the end of Cycle 1 (each cycle is 28 days)
Phase Ib: To evaluate the efficacy of GNTbm-38 in patients with R/R PTCL.
Phase 1b dose expansion cohort will be initiated following the MTD from Phase Ia to further evaluate the safety and preliminary efficacy of GNTbm-38 in patients with R/R PTCL, response will be defined by the Lugano criteria.
Time frame: At the end of Cycle 1 (each cycle is 28 days)
Maximum plasma concentration (Cmax)
To characterize the PK of GNTbm-38
Time frame: At the end of Cycle 1 (each cycle is 28 days)
Time to reach maximum concentration (Tmax)
To characterize the PK of GNTbm-38
Time frame: At the end of cycle 1 (each cycle is 28 days)
Area under the plasma concentration-time curve (AUC)
To characterize the PK of GNTbm-38
Time frame: At the end of Cycle 1 (each cycle is 28 days)
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Trough concentration (Ctrough)
To characterize the PK of GNTbm-38
Time frame: From Cycle 1 Day 1 (each cycle is 28 days) until End of Treatment