This is a first-in-human (FIH), exploratory, multicenter, open-label, phase I/II study of ABSK141 in patients with advanced solid tumors to to evaluate safety, tolerability, PK and optimize the dosage.
The study will start with a dose escalation of oral ABSK141 in patients with advanced solid tumors harboring KRAS G12D mutation to evaluate safety, tolerability, and PK. The expansion part will investigate oral ABSK141 at the recommended doses for expansion (RDEs) to evaluate safety and efficacy among selected tumor types harboring KRAS G12D mutation and optimize the dosage. The phase II study will further investigate oral ABSK141 at the recommended phase 2 doses (RP2Ds) to evaluate safety and efficacy among selected tumor types harboring KRAS G12D mutation.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
401
In the escalation part#patients will first orally receive a single dose of ABSK141 on D-3, followed by a three-day run-in period to assess the PK profile of singledose ABSK141 400mg administration. Thereafter, patients will continuously receive ABSK141 400mg once daily (QD).
In the expansion part# patients will orally receive ABSK141 at the recommended dose for expansion (RDE).patients will continuously receive ABSK141 Recommended Dose for Expansion (RDE) once daily (QD).
In the escalation part#patients will first orally receive a single dose of ABSK141 on D-3, followed by a three-day run-in period to assess the PK profile of singledose ABSK141 800mg administration. Thereafter, patients will continuously receive ABSK141 800mg once daily (QD).
Fudan University Shanghai Cancer Center
Shanghai, China
RECRUITINGIncidence of DLTs
dose-limiting toxicities
Time frame: from Run-in to Day28
Incidence and severity of AEs
Adverse events
Time frame: from the time that the patient provides informed consent through and including 30 days after the last administration of ABSK141.
Incidence and severity of SAEs
serious adverse events
Time frame: from the time that the patient provides informed consent through and including 30 days after the last administration of ABSK141.
Cmax
maximum observed concentration
Time frame: From pre-dose to up to 72 hours post-dose
AUC
area under the concentration-time curve
Time frame: From pre-dose to up to 72 hours post-dose
t1/2
elimination half-life
Time frame: From pre-dose to up to 72 hours post-dose
CL/F
apparent oral clearance
Time frame: From pre-dose to up to 72 hours post-dose
tmax
time to maximum observed concentration
Time frame: From pre-dose to up to 72 hours post-dose
ORR
Objective response rate
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In the escalation part#patients will first orally receive a single dose of ABSK141 on D-3, followed by a three-day run-in period to assess the PK profile of singledose ABSK141 1200mg administration. Thereafter, patients will continuously receive ABSK141 1200mg once daily (QD).
Phase II #patients will orally receive ABSK141 at the Recommended Phase 2 Dose (RP2D).
Time frame: From the first dose date to the date of first confirmed response (CR/PR), assessed up to 24 months.
DOR
Duration of response
Time frame: From date of first confirmed response (CR/PR) to date of first documented progression (PD) or death from any cause, whichever comes first, assessed up to 24 months.
PFS
Progression-free survival
Time frame: From the first dose date to the date of first documented progressive disease (PD) or death from any cause, whichever occurs first, assessed up to 24 months.
DCR
Disease control rate
Time frame: From the first dose date to the date of first documented disease status assessment (CR/PR/SD/PD), assessed up to 24 months.
OS
Overall survival
Time frame: From the first dose date to the date of death from any cause, assessed up to24 months