Outcome
Type |
Measure |
Description |
Time frame |
Safety issue |
Primary |
Incidence of Adverse Events |
Defined by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE V5.0) |
The period of AE collection starts after the participant receives the investigational drug, until 28±3 days after the EOT/early withdrawal or before the participant starts another anti-tumor treatment (whichever occurs first). |
|
Primary |
Incidence of dose-limiting toxicities(DLT) |
Observe the dose limiting toxicity, and Incidence of dose-limiting toxicities(DLT) will be assessed |
The DLT evaluation period is from the first administration of the investigational drug to the end of the first treatment cycle, lasting for 21 days.(only Ia) |
|
Primary |
Red blood cell count in whole blood sample |
Changes from baseline for Red blood cell count in whole blood |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
White blood cell in whole blood sample |
Changes from baseline for white blood cell count in whole blood |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Hematocrit in whole blood sample |
Changes from baseline for Hematocrit in whole blood |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Neutrophil count in whole blood sample |
Changes from baseline for neutrophil count in whole blood |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Hemoglobin concentration in whole blood sample |
Changes from baseline for hemoglobin concentration in whole blood |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Percentage of lymphocytes (LYM%) |
Changes from baseline for Percentage of lymphocytes (LYM%) in whole blood |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Lymphocyte count |
Changes from baseline for Lymphocyte count in whole blood |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Percentage of neutrophils (NEU%) Percentage of neutrophils (NEU%) |
Changes from baseline for Percentage of neutrophils (NEU%) in whole blood |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Platelet count in whole blood sample |
Changes from baseline for Platelet count in whole blood |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Prothrombin time in whole blood sample |
Changes from baseline for Prothrombin time in whole blood sample |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
International normalized ratio in whole blood sample |
Changes from baseline for international standardized ratio in whole blood sample |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Fibrinogen in whole blood sample |
Changes from baseline for Fibrinogen in whole blood |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Activated partial prothrombin time in whole blood sample |
Changes from baseline for activated partial thromboplastin time in whole blood sample |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Total bilirubin concentration in whole blood sample |
Changes from baseline for total bilirubin concentration in whole blood sample |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
ALT concentration in whole blood sample |
Changes from baseline for alanine aminotransferase(ALT) concentration in whole blood sample |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
AST concentration in whole blood sample |
Changes from baseline for aspartate aminotransferase(AST) concentration in whole blood sample |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Total protein concentration in whole blood sample |
Changes from baseline for total protein concentration in whole blood sample |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Urea concentration in whole blood sample |
Changes from baseline for urea concentration in whole blood sample |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Creatinine concentration in whole blood sample |
Changes from baseline for creatinine concentration in whole blood sample |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Total cholesterol concentration in whole blood sample |
Changes from baseline for total cholesterol concentration in whole blood sample |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Triglycerides concentration in whole blood sample |
Changes from baseline for triglycerides concentration in whole blood sample |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
HDL-C in whole blood sample |
Changes from baseline for high density lipoprotein cholesterol (HDL-C) in whole blood sample |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
LDL-C in whole blood sample |
Changes from baseline for low density lipoprotein cholesterol (LDL-C) in whole blood sample |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Glucose in whole blood sample |
Changes from baseline for Lactic dehydrogenase in whole blood |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Alkaline phosphatase in whole blood sample |
Changes from baseline for Lactic dehydrogenase in whole blood |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Lactic dehydrogenase in whole blood sample |
Changes from baseline for Lactic dehydrogenase in whole blood |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Gamma-glutamyl transferase in whole blood sample |
Changes from baseline for Gamma-glutamyl transferase in whole blood |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Albumin in whole blood sample |
Changes from baseline for Albumin in whole blood |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Direct bilirubin in whole blood sample |
Changes from baseline for Direct bilirubin in whole blood |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Sodium in whole blood sample |
Changes from baseline for Sodium in whole blood |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Potassium in whole blood sample |
Changes from baseline for Potassium in whole blood |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Chloride in whole blood sample |
Changes from baseline for Chloride in whole blood |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Calcium in whole blood sample |
Changes from baseline for Calcium in whole blood |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Phosphate in whole blood sample |
Changes from baseline for Phosphate in whole blood |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Uric acid in whole blood sample |
Changes from baseline for Uric acid in whole blood |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Creatine kinase in whole blood sample |
Changes from baseline for Creatine kinase in whole blood |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Creatine kinase isoenzyme in whole blood sample |
Changes from baseline for Creatine kinase isoenzyme in whole blood |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Troponin-T (TnT) in whole blood sample |
Changes from baseline for Troponin-T in whole blood |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Troponin-I (TnI) in whole blood sample |
Changes from baseline for Troponin-I in whole blood |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Urine protein in urine sample |
Changes from baseline for Urine protein in urine sample |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Red blood cells in urine sample |
Changes from baseline for Red blood cells in urine sample |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
White blood cells in urine sample |
Changes from baseline for White blood cells in urine sample |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
PH in urine sample |
Changes from baseline for pH in urine sample |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Ketone bodies in urine sample |
Changes from baseline for Ketone bodies in urine sample |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Urine glucose in urine sample |
Changes from baseline for Urine glucose in urine sample |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Urine bilirubin in urine sample |
Changes from baseline for Urine bilirubin in urine sample |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Urine occult blood in urine sample |
Changes from baseline for Urine occult blood in urine sample |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Heart Rate in beats per minute in beats per minute of ECG |
Changes from baseline for heart rate in beats per minute |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
RR Interval by ECG |
Changes from baseline for RR interval by ECG |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
PR Interval by ECG |
Changes from baseline for PR interval by ECG |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
QRS Interval by ECG |
Changes from baseline for QRS interval by ECG |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
QT Interval by ECG |
Changes from baseline for QT interval by ECG |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
QTcF by ECG |
Changes from baseline for QTcF interval by ECG |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Left ventricular ejection fraction measured by Echocardiography |
Changes from baseline for Left ventricular ejection fraction measured by Echocardiography |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Body (Ear) Temperature measurement in Vital Signs |
Changes from baseline for Body (Ear) Temperature |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Pulse measurement in Vital Signs |
Changes from baseline for Pulse |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Respiration Rate measurement in Vital Signs |
Changes from baseline for respiration rate in breaths of Vital Signs |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Sitting Systolic Blood Pressure |
Changes from baseline for Sitting Systolic Blood Pressure |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
Sitting Diastolic Blood Pressure |
Changes from baseline for Sitting Diastolic Blood Pressure |
This should be evaluated during the screening period, on Day 1, 8, 15 of each cycle (each cycle is 21 days) , Day 1 of each subsequent cycle, at the EOT/early withdrawal and safety follow-up. |
|
Primary |
The recommended Phase II dose |
Determine the Recommended Phase II Dose(mg/?) of HF158K1 and provide references for dose selection in future clinical studies. |
After the end of the dose Expansion Phase(only Ib) |
|
Primary |
Determine the maximum tolerated dose |
The dose at which the incidence of DLT was closest to the target probability of toxicity (30%). |
The first administration of the investigational drug to the end of the first treatment cycle, lasting for 21 days. |
|
Secondary |
HF158K1 pharmacokinetic parameters with Cmax |
Maximum plasma concentration (Cmax) after administration of HF158K1 |
Within 336 hours after the first and second administration |
|
Secondary |
AUC by plasma concentration of whole blood sample |
Area under plasma concentration -time curve after dose |
Within 336 hours after the first and second administration |
|
Secondary |
Tmax by plasma concentration of whole blood sample |
Peak time (Tmax) after dose |
Within 336 hours after the first and second administration |
|
Secondary |
T1/2 by plasma concentration of whole blood sample |
Elimination half-life (T1/2) after dose |
Within 336 hours after the first and second administration |
|
Secondary |
CL by plasma concentration of whole blood sample |
Clearance (CL) after dose |
Within 336 hours after the first and second administration |
|
Secondary |
Vd by plasma concentration of whole blood sample |
Volume of distribution(Vd) after dose |
Within 336 hours after the first and second administration |
|
Secondary |
AUClast by plasma concentration of whole blood sample |
Ratios of geometric means of AUClast (Area under the plasma concentration-time curve from zero to time of last quantifiable concentration) after dose |
Within 336 hours after the first and second administration |
|
Secondary |
The objective response rate(ORR) of HF158K1 |
ORR is defined as the proportion of participants with complete response or partial response (CR+PR) |
ORR will be calculated for all participants who have received the investigational drug at least once and have undergone at least one tumor evaluation after administration, assessed up to 51 weeks. |
|
Secondary |
disease control rate (DCR) of HF158K1 |
DCR is defined as the proportion of participants with complete response stable disease and partial response (CR+PR+SD) |
DCR will be calculated for all participants who have received the investigational drug at least once and have undergone at least one tumor evaluation after administration, assessed up to 51 weeks. |
|
Secondary |
duration of response(DOR) of HF158K1 |
For duration of response (DOR), the Kaplan-Meier survival curve will be plotted to analyze their maximum, minimum, median and 95% confidence interval descriptively statistically. |
DOR will be calculated for all participants who have received the investigational drug at least once and have undergone at least one tumor evaluation after administration, assessed up to 51 weeks. |
|
Secondary |
Analysis of immunogenicity |
Immunogenicity analyses related to anti-TL01 antibody will be performed based on IMS(Immunogenicity Analysis Set). |
On the first day of the first cycle, on the first day of the fourth cycle, on the 21st day of the eighth cycle |
|