The study is being conducted to determine the dose limited toxicity(DLT) and maximum tolerated dose(MTD) and recommended Phase 2 dose(RP2D) of HRS2398 in subjects with advanced malignant tumor ; The second objectives is to evaluate safety and preliminary efficacy and PK profile of HRS2398 in subjects with advanced malignant tumor ; Exploratory cohort is to explore the relationship between gene mutation and efficacy and resistance mechanisms.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
28
Take 5mg to 320mg once or twice a day ; Oral administration , 21 days as a cycle.
Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital
Zhengzhou, Henan, China
Dose-limiting toxicity(DLT)
Time frame: up to 21 days
Maximum tolerated dose(MTD)
Time frame: up to 6 months
Recommended Phase II Dose (RP2D)
Time frame: up to 21 days
Number of subjects with adverse events and the severity of adverse events
Time frame: from the first drug administration to within 30 days for the last treatment dose
Cmax of HRS2398 of Single administration
Time frame: Single administration : 30min before administration of Day1, 5min, 0.25 hour, 0.5 hour, 0.75 hour, 1 hour , 2hours, 4hours, 6hours, 8hours, 10hours, 24hours, 48hours, 72hours after administration of Day1
Tmax of HRS2398 of Single administration
Time frame: Single administration : 30min before administration of Day1, 5min, 0.25 hour, 0.5 hour, 0.75 hour, 1 hour , 2hours, 4hours, 6hours, 8hours, 10hours, 24hours, 48hours, 72hours after administration of Day1
AUC0-t of HRS2398 of Single administration
Time frame: ingle administration : 30min before administration of Day1, 5min, 0.25 hour, 0.5 hour, 0.75 hour, 1 hour , 2hours, 4hours, 6hours, 8hours, 10hours, 24hours, 48hours, 72hours after administration of Day1
AUC0-12 of HRS2398 of Single administration
Time frame: Single administration : 30min before administration of Day1, 5min, 0.25 hour, 0.5 hour, 0.75 hour, 1 hour , 2hours, 4hours, 6hours, 8hours, 10hours after administration of Day1
T1/2 of HRS2398 of Single administration
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Time frame: Single administration : 30min before administration of Day1, 5min, 0.25 hour, 0.5 hour, 0.75 hour, 1 hour , 2hours, 4hours, 6hours, 8hours, 10hours, 24hours, 48hours, 72hours after administration of Day1
Cmax of HRS2398 of Multiple doses
Time frame: Multiple administration: Day8, Day15, Day17 of Cycle1, Day1 of Cycle2-4 (each cycle is 21 days)
Tmax of HRS2398 of Multiple administration
Time frame: Multiple administration: Day8, Day15, Day17 of Cycle1, Day1 of Cycle2-4 (each cycle is 21 days)
AUC0-t of HRS2398 of Multiple administration
Time frame: Multiple administration: Day8, Day15, Day17 of Cycle1, Day1 of Cycle2-4 (each cycle is 21 days)
AUC0-12 of HRS2398 of Multiple administration
Time frame: Multiple administration: Day8, Day15, Day17 of Cycle1, Day1 of Cycle2-4 (each cycle is 21 days)
T1/2 of HRS2398 of Multiple administration
Time frame: Multiple administration: Day8, Day15, Day17 of Cycle1, Day1 of Cycle2-4 (each cycle is 21 days)
Bioavailability of fasting state
PK blood samples from subjects were collected for bioavailability ,Postprandial AUC divided by fasting AUC
Time frame: up to 4 months
Objective Response Rate(ORR)
Radiological scans performed at baseline then every 6 weeks until objective radiological disease progression
Time frame: up to 4 months
Disease Control Rate(DCR)
Complete response + Partial response + Stable disease (CR+PR+SD) based on RECIST 1.1
Time frame: up to 4 months
Duration of response (DoR)
Time from documentation of tumor response to disease progression assessed among patients who had an objective response
Time frame: up to 4 months
Progression free survival(PFS)
Defined as Progression free survival per RECIST 1.1 criteria according to Investigator's assessment
Time frame: up to 4 months