This is an open-label phase 1 study with an escalation part and an expansion part.
The escalation part will evaluate the safety, tolerability, PK and recommended dose of expansion (RDE) of oral ABSK-011 in patients with advanced solid tumors. The expansion part of oral ABSK-011 at RDE will be followed for further evaluating safety and tolerability in patients with FGF19 overexpression advanced HCC. Preliminary antitumor activity will also be assessed.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
200
During the escalation part, the administration of oral ABSK-011 will be guided by "3+3"design based on safety data collected until a maximum tolerated dose (MTD) has been identified. The first dose level will be administered as QD, and different dosing frequencies (e.g., BID) may be explored in subsequent doses depending on emerging safety and pharmacokinetic data. A separate food effect cohort may be conducted. In expansion part, patients will be treated at the selected RDE dose level.
Incidence of DLT
Incidence of dose-limiting toxicities (DLTs) in Cycle 1
Time frame: From the starting dosing of study drug to the end of Cycle 1 (each cycle is 28 days) in escalation Part
Incidence and severity of AEs, AESIs and SAEs
Incidence and severity of adverse events (AEs), adverse events of special interest (AESIs) and serious adverse events (SAEs) (Common Terminology Criteria for Adverse Events, CTCAE 5.0)
Time frame: 30 days after last administration, an average of one half year
dose reduction or discontinuation
dose reduction or discontinuation of study drug due to toxicity
Time frame: through study completion, an average of one half year
physical examinations changes from baseline
BMI
Time frame: through study completion, an average of one half year
ECOG performance status
ECOG performance status
Time frame: through study completion, an average of one half year
electrocardiograms (ECGs)
QTc
Time frame: through study completion, an average of one half year
echocardiograms changes from baseline
EF%
Time frame: through study completion, an average of one half year
vital signs changes from baseline
Temperature
Time frame: through study completion, an average of one half year
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Mayo Clinic
Phoenix, Arizona, United States
RECRUITINGMayo Clinic
Jacksonville, Florida, United States
RECRUITINGMoffitt Cancer Center
Tampa, Florida, United States
RECRUITINGMayo Clinic
Rochester, Minnesota, United States
RECRUITINGIcahn School of Medicine at Mount Sinai
New York, New York, United States
RECRUITINGMD Anderson Cancer Center
Houston, Texas, United States
RECRUITINGThe First Affiliated Hospital of Bengbu Medical College
Bengbu, Anhui, China
COMPLETEDBeijing Tsinghua Changgung Hospital
Beijing, Beijing Municipality, China
RECRUITINGThe Fifth Medical Center of the General Hospital of the Chinese People's Liberation Army
Beijing, Beijing Municipality, China
WITHDRAWNChongqing Cancer Hospital
Chongqing, Chongqing Municipality, China
RECRUITING...and 22 more locations
vital signs changes from baseline
pulse
Time frame: through study completion, an average of one half year
vital signs changes from baseline
blood pressure
Time frame: through study completion, an average of one half year
Cmax
maximum observed concentration (Cmax)
Time frame: the end of Cycle 1 Day15 (each cycle is 28 days)
Tmax
time to maximum observed concentration (Tmax)
Time frame: the end of Cycle 1 Day15 (each cycle is 28 days)
AUC
area under the concentration-time curve (AUC)
Time frame: the end of Cycle 1 Day15 (each cycle is 28 days)
t1/2β
elimination half-life (t1/2β)
Time frame: the end of Cycle 1 Day15 (each cycle is 28 days)
Vz/F
apparent volume of distribution (Vz/F)
Time frame: the end of Cycle 1 Day15 (each cycle is 28 days)
CL/F
apparent oral clearance (CL/F)
Time frame: the end of Cycle 1 Day15 (each cycle is 28 days)
Css_max
maximum observed concentration of steady-state (Css\_max)
Time frame: the end of Cycle 1 Day15 (each cycle is 28 days)
Css_min
minimum observed concentration of steady-state (Css\_min)
Time frame: the end of Cycle 1 Day15 (each cycle is 28 days)
AUCss
area under the concentration-time curve of steady-state (AUCss)
Time frame: the end of Cycle 1 Day15 (each cycle is 28 days)
Rac
accumulation rate (Rac)
Time frame: the end of Cycle 1 Day15 (each cycle is 28 days)
ORR
Evaluate the preliminary antitumor activity in patients with FGF19 overexpression advanced HCC and in patients with other types of advanced solid tumor
Time frame: throughout study completion, on average of half year
DoR
Duration of response (DoR): time from \[PR\] or \[CR\] to disease progression
Time frame: throughout study completion, on average of half year
DCR
Disease control rate (DCR): DCR = \[CR\] +\[PR\] + stable disease \[SD\]
Time frame: throughout study completion, on average of half year
PFS
Progression-free survival (PFS): time from the first day receive study drug to disease progression or death
Time frame: throughout study completion, on average of half year