A Phase 1 Clinical Study to Investigate the Safety, Tolerability, and Preliminary Efficacy of HF158K1 in Participants With HER-2 Expressing Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 84
- 试验地点
- 3
- 主要终点
- Hemoglobin concentration in whole blood sample
研究概览
简要总结
HF158K1 is an investigational liposome form of doxorubicin hydrochloride, an anthracycline topoisomerase inhibitor, encapsulated by lipid membranes containing TL01, a HER2-directed Trastuzumab Fab fragment conjugated lipid.
详细描述
This study is a multi-regional, open-label, multiple-dose administration dose-escalation and dose-expansion study, including a Dose-Escalation Phase (Ia) and a Dose-Expansion Phase (Ib).
HF158K1 contains multiple copies of the targeting antibody on liposome surface. It is designed to bind and deliver the chemotherapeutic doxorubicin to tumor cells at even very low HER2 expression levels. The study recruits patients with unresectable or metastatic advanced solid tumors (HER-2 positive (IHC 3+, or IHC 2+ with ISH +) or HER-2 low expression (IHC 2+ with ISH -, or IHC 1+)) who have failed or are intolerant (disease progression, or intolerance to chemotherapy, targeted therapy, etc.) to standard treatment, or currently have no available treatment regimen.
Phase 1a(Dose escalation) will assess the safety，tolerability，pharmacokinetics of HF158K1 in participants to determine the maximum tolerated dose (MTD) of HF158K1 through the incidence of dose-limiting toxicity (DLT).
Phase 1b (Dose bridging) will be conducted in Chinese patients to bridge the safety and pharmacokinetic data between different ethnic populations.
Phase 1c(Dose expansion) will assess safety and preliminary efficacy of HF158K1 in participants with specific tumor types in selected dose groups.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntary to participate and sign ICF.
- •Age ≥ 18 and ≤ 75 years.
- •Unresectable or metastatic advanced solid tumors with HER-2 expression (IHC 3+, 2+, or 1+).
- •ECOG score 0-
- •Expected survival ≥ 6 months.
- •At least one measurable lesion per RECIST v1.
- •Adequate organ function: ANC ≥ 1.5×10⁹/L, LYM ≥ 1.0×10⁹/L, PLT ≥ 90×10⁹/L, HGB ≥ 8.0 g/dL; APTT ≤ 1.5×ULN, INR ≤ 1.5; TBIL ≤ 1.5×ULN, ALT/AST ≤ 2.5×ULN (≤ 5×ULN if liver metastases); CrCl ≥ 30 mL/min; LVEF ≥ 50%.
- •Agreement to use effective contraception.
排除标准
- •Cumulative doxorubicin dose ≥ 350 mg/m² or prior anthracycline-induced cardiotoxicity.
- •Current use of immunosuppressants or systemic corticosteroids (> 10 mg/day prednisone).
- •Prior anti-tumor therapy < 2 weeks (4 weeks for nitrosourea/mitomycin C).
- •Symptomatic CNS metastases.
- •Unresolved AEs from prior therapy > Grade
- •Serious cardiovascular diseases (thromboembolic events within 3 months, NYHA III-IV, ACS within 6 months, or uncontrolled hypertension).
- •Active infection or unexplained fever > 38.5°C.
- •HIV, active HBV or HCV.
- •Pregnant or breastfeeding.
研究组 & 干预措施
Dose escalation: HF158K1 1.4 g lipid dose
Participants in this dose group (1.4 g lipid dose) will receive HF158K1 on D1 of each treatment cycle (3 weeks as a treatment cycle) through intravenous infusion.
干预措施: HF158K1 / 1.4 g lipid dose (Drug)
Dose escalation: HF158K1 2.2 g lipid dose
Participants in this dose group (2.2 g lipid dose) will receive HF158K1 on D1 of each treatment cycle (3 weeks as a treatment cycle) through intravenous infusion.
干预措施: HF158K1 / 2.2 g lipid dose (Drug)
Dose escalation: HF158K1 2.9 g lipid dose
Participants in this dose group (2.9 g lipid dose) will receive HF158K1 on D1 of each treatment cycle (3 weeks as a treatment cycle) through intravenous infusion.
干预措施: HF158K1 / 2.9 g lipid dose (Drug)
结局指标
主要结局
Hemoglobin concentration in whole blood sample
时间窗: 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.
Changes from baseline for hemoglobin concentration in whole blood
Triglycerides concentration in whole blood sample
时间窗: 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.
Changes from baseline for triglycerides concentration in whole blood sample
HDL-C in whole blood sample
时间窗: 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.
Changes from baseline for high density lipoprotein cholesterol (HDL-C) in whole blood sample
Neutrophil count in whole blood sample
时间窗: 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.
Changes from baseline for neutrophil count in whole blood
Incidence of dose-limiting toxicities(DLT)
时间窗: 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）
Observe the dose limiting toxicity, and Incidence of dose-limiting toxicities(DLT) will be assessed
Red blood cell count in whole blood sample
时间窗: 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.
Changes from baseline for Red blood cell count in whole blood
Chloride in whole blood sample
时间窗: 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.
Changes from baseline for Chloride in whole blood
White blood cell in whole blood sample
时间窗: 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.
Changes from baseline for white blood cell count in whole blood
International normalized ratio in whole blood sample
时间窗: 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.
Changes from baseline for international standardized ratio in whole blood sample
ALT concentration in whole blood sample
时间窗: 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.
Changes from baseline for alanine aminotransferase(ALT) concentration in whole blood sample
AST concentration in whole blood sample
时间窗: 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.
Changes from baseline for aspartate aminotransferase(AST) concentration in whole blood sample
Total cholesterol concentration in whole blood sample
时间窗: 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.
Changes from baseline for total cholesterol concentration in whole blood sample
Lactic dehydrogenase in whole blood sample
时间窗: 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.
Changes from baseline for Lactic dehydrogenase in whole blood
Sodium in whole blood sample
时间窗: 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.
Changes from baseline for Sodium in whole blood
Uric acid in whole blood sample
时间窗: 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.
Changes from baseline for Uric acid in whole blood
White blood cells in urine sample
时间窗: 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.
Changes from baseline for White blood cells in urine sample
Incidence of Adverse Events
时间窗: 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).
Defined by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE V5.0)
Hematocrit in whole blood sample
时间窗: 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.
Changes from baseline for Hematocrit in whole blood
Percentage of lymphocytes (LYM%)
时间窗: 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.
Changes from baseline for Percentage of lymphocytes (LYM%) in whole blood
Lymphocyte count
时间窗: 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.
Changes from baseline for Lymphocyte count in whole blood
Percentage of neutrophils (NEU%) Percentage of neutrophils (NEU%)
时间窗: 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.
Changes from baseline for Percentage of neutrophils (NEU%) in whole blood
Activated partial prothrombin time in whole blood sample
时间窗: 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.
Changes from baseline for activated partial thromboplastin time in whole blood sample
LDL-C in whole blood sample
时间窗: 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.
Changes from baseline for low density lipoprotein cholesterol (LDL-C) in whole blood sample
Direct bilirubin in whole blood sample
时间窗: 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.
Changes from baseline for Direct bilirubin in whole blood
Troponin-T (TnT) in whole blood sample
时间窗: 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.
Changes from baseline for Troponin-T in whole blood
Platelet count in whole blood sample
时间窗: 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.
Changes from baseline for Platelet count in whole blood
Prothrombin time in whole blood sample
时间窗: 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.
Changes from baseline for Prothrombin time in whole blood sample
Total protein concentration in whole blood sample
时间窗: 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.
Changes from baseline for total protein concentration in whole blood sample
Creatinine concentration in whole blood sample
时间窗: 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.
Changes from baseline for creatinine concentration in whole blood sample
Calcium in whole blood sample
时间窗: 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.
Changes from baseline for Calcium in whole blood
Phosphate in whole blood sample
时间窗: 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.
Changes from baseline for Phosphate in whole blood
Fibrinogen in whole blood sample
时间窗: 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.
Changes from baseline for Fibrinogen in whole blood
Total bilirubin concentration in whole blood sample
时间窗: 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.
Changes from baseline for total bilirubin concentration in whole blood sample
Urea concentration in whole blood sample
时间窗: 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.
Changes from baseline for urea concentration in whole blood sample
Alkaline phosphatase in whole blood sample
时间窗: 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.
Changes from baseline for Lactic dehydrogenase in whole blood
Potassium in whole blood sample
时间窗: 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.
Changes from baseline for Potassium in whole blood
Glucose in whole blood sample
时间窗: 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.
Changes from baseline for Lactic dehydrogenase in whole blood
Gamma-glutamyl transferase in whole blood sample
时间窗: 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.
Changes from baseline for Gamma-glutamyl transferase in whole blood
Albumin in whole blood sample
时间窗: 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.
Changes from baseline for Albumin in whole blood
Creatine kinase in whole blood sample
时间窗: 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.
Changes from baseline for Creatine kinase in whole blood
PH in urine sample
时间窗: 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.
Changes from baseline for pH in urine sample
Sitting Systolic Blood Pressure
时间窗: 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.
Changes from baseline for Sitting Systolic Blood Pressure
Creatine kinase isoenzyme in whole blood sample
时间窗: 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.
Changes from baseline for Creatine kinase isoenzyme in whole blood
QT Interval by ECG
时间窗: 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.
Changes from baseline for QT interval by ECG
QTcF by ECG
时间窗: 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.
Changes from baseline for QTcF interval by ECG
Body (Ear) Temperature measurement in Vital Signs
时间窗: 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.
Changes from baseline for Body (Ear) Temperature
Determine the maximum tolerated dose
时间窗: The first administration of the investigational drug to the end of the first treatment cycle, lasting for 21 days.
The dose at which the incidence of DLT was closest to the target probability of toxicity (30%).
Troponin-I (TnI) in whole blood sample
时间窗: 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.
Changes from baseline for Troponin-I in whole blood
Urine protein in urine sample
时间窗: 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.
Changes from baseline for Urine protein in urine sample
Red blood cells in urine sample
时间窗: 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.
Changes from baseline for Red blood cells in urine sample
Urine glucose in urine sample
时间窗: 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.
Changes from baseline for Urine glucose in urine sample
Urine bilirubin in urine sample
时间窗: 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.
Changes from baseline for Urine bilirubin in urine sample
Heart Rate in beats per minute in beats per minute of ECG
时间窗: 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.
Changes from baseline for heart rate in beats per minute
PR Interval by ECG
时间窗: 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.
Changes from baseline for PR interval by ECG
Sitting Diastolic Blood Pressure
时间窗: 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.
Changes from baseline for Sitting Diastolic Blood Pressure
The recommended Phase II dose
时间窗: After the end of the dose Expansion Phase（only Ib）
Determine the Recommended Phase II Dose(mg/㎡) of HF158K1 and provide references for dose selection in future clinical studies.
Ketone bodies in urine sample
时间窗: 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.
Changes from baseline for Ketone bodies in urine sample
RR Interval by ECG
时间窗: 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.
Changes from baseline for RR interval by ECG
QRS Interval by ECG
时间窗: 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.
Changes from baseline for QRS interval by ECG
Left ventricular ejection fraction measured by Echocardiography
时间窗: 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.
Changes from baseline for Left ventricular ejection fraction measured by Echocardiography
Pulse measurement in Vital Signs
时间窗: 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.
Changes from baseline for Pulse
Urine occult blood in urine sample
时间窗: 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.
Changes from baseline for Urine occult blood in urine sample
Respiration Rate measurement in Vital Signs
时间窗: 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.
Changes from baseline for respiration rate in breaths of Vital Signs
Red blood cell count in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Red blood cell count in whole blood
White blood cell in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for white blood cell count in whole blood
Hematocrit in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Hematocrit in whole blood
Neutrophil count in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for neutrophil count in whole blood
Hemoglobin concentration in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for hemoglobin concentration in whole blood
Percentage of lymphocytes (LYM%)
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Percentage of lymphocytes (LYM%) in whole blood
Lymphocyte count
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Lymphocyte count in whole blood
Percentage of neutrophils (NEU%) Percentage of neutrophils (NEU%)
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Percentage of neutrophils (NEU%) in whole blood
Platelet count in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Platelet count in whole blood
Prothrombin time in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Prothrombin time in whole blood sample
International normalized ratio in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for international standardized ratio in whole blood sample
Fibrinogen in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Fibrinogen in whole blood
Activated partial prothrombin time in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for activated partial thromboplastin time in whole blood sample
Total bilirubin concentration in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for total bilirubin concentration in whole blood sample
ALT concentration in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for alanine aminotransferase(ALT) concentration in whole blood sample
AST concentration in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for aspartate aminotransferase(AST) concentration in whole blood sample
Total protein concentration in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for total protein concentration in whole blood sample
Urea concentration in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for urea concentration in whole blood sample
Creatinine concentration in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for creatinine concentration in whole blood sample
Total cholesterol concentration in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for total cholesterol concentration in whole blood sample
Triglycerides concentration in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for triglycerides concentration in whole blood sample
HDL-C in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for high density lipoprotein cholesterol (HDL-C) in whole blood sample
LDL-C in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for low density lipoprotein cholesterol (LDL-C) in whole blood sample
Glucose in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Lactic dehydrogenase in whole blood
Alkaline phosphatase in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Lactic dehydrogenase in whole blood
Lactic dehydrogenase in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Lactic dehydrogenase in whole blood
Gamma-glutamyl transferase in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Gamma-glutamyl transferase in whole blood
Albumin in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Albumin in whole blood
Direct bilirubin in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Direct bilirubin in whole blood
Sodium in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Sodium in whole blood
Potassium in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Potassium in whole blood
Chloride in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Chloride in whole blood
Calcium in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Calcium in whole blood
Phosphate in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Phosphate in whole blood
Uric acid in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Uric acid in whole blood
Creatine kinase in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Creatine kinase in whole blood
Creatine kinase isoenzyme in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Creatine kinase isoenzyme in whole blood
Troponin-T (TnT) in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Troponin-T in whole blood
Troponin-I (TnI) in whole blood sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Troponin-I in whole blood
Urine protein in urine sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Urine protein in urine sample
Red blood cells in urine sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Red blood cells in urine sample
White blood cells in urine sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for White blood cells in urine sample
PH in urine sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for pH in urine sample
Ketone bodies in urine sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Ketone bodies in urine sample
Urine glucose in urine sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Urine glucose in urine sample
Urine bilirubin in urine sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Urine bilirubin in urine sample
Urine occult blood in urine sample
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Urine occult blood in urine sample
Heart Rate in beats per minute in beats per minute of ECG
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for heart rate in beats per minute
RR Interval by ECG
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for RR interval by ECG
PR Interval by ECG
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for PR interval by ECG
QRS Interval by ECG
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for QRS interval by ECG
QT Interval by ECG
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for QT interval by ECG
QTcF by ECG
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for QTcF interval by ECG
Left ventricular ejection fraction measured by Echocardiography
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Left ventricular ejection fraction measured by Echocardiography
Body (Ear) Temperature measurement in Vital Signs
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Body (Ear) Temperature
Pulse measurement in Vital Signs
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Pulse
Respiration Rate measurement in Vital Signs
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for respiration rate in breaths of Vital Signs
Sitting Systolic Blood Pressure
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Sitting Systolic Blood Pressure
Sitting Diastolic Blood Pressure
时间窗: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)
Changes from baseline for Sitting Diastolic Blood Pressure
The recommended Phase II dose
时间窗: After the end of the dose Expansion Phase（only Ic）
Determine the Recommended Phase II Dose(mg/㎡) of HF158K1 and provide references for dose selection in future clinical studies.
次要结局
- HF158K1 pharmacokinetic parameters with Cmax(Within 336 hours after the first and second administration)
- Analysis of immunogenicity(On the first day of the first cycle, on the first day of the fourth cycle, on the 21st day of the eighth cycle)
- AUC by plasma concentration of whole blood sample(Within 336 hours after the first and second administration)
- AUClast by plasma concentration of whole blood sample(Within 336 hours after the first and second administration)
- disease control rate (DCR) of HF158K1(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.)
- duration of response(DOR) of HF158K1(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.)
- Tmax by plasma concentration of whole blood sample(Within 336 hours after the first and second administration)
- CL by plasma concentration of whole blood sample(Within 336 hours after the first and second administration)
- Vd by plasma concentration of whole blood sample(Within 336 hours after the first and second administration)
- The objective response rate(ORR) of HF158K1(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.)
- T1/2 by plasma concentration of whole blood sample(Within 336 hours after the first and second administration)