A Clinical Study to Investigate the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Preliminary Efficacy of HF158K1 in Participants With HER-2 Positive or HER-2 Low Expression Advanced Solid Tumors

Solid Tumors, Adult Clinical Trial

Official title:

A Multi-Regional, Open-Label, Dose Escalation and Dose Expansion Phase Ⅰ Clinical Study to Investigate the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Preliminary Efficacy of HF158K1 in Participants With HER-2 Positive or HER-2 Low Expression Advanced Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05861895
• Other study ID #: HF158K1-101
• Status: Recruiting
• Phase: Phase 1
• Start date: December 12, 2023
• Est. completion date: December 22, 2025

Study information

• Verified date: December 2023
• Source: HighField Biopharmaceuticals Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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 expansion) will assess safety and preliminary efficacy of HF158K1 in participants with specific tumor types in selected dose groups.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 84
• Est. completion date: December 22, 2025
• Est. primary completion date: April 23, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 1. Voluntary to participate in the clinical study, sign a written informed consent form, and able to comply with clinical visits and study-related procedures.

2. Male or female participants at least 18 years old when signing the informed consent form.

3. ECOG performance score of 0 to 1 point. 4. Study population: HER-2 positive (IHC 3+, or IHC 2+ with ISH +) or HER-2 low expression (IHC 2+ with ISH -, or IHC 1+) participants with unresectable or metastatic advanced solid tumors (confirmed by histopathology or cytology analysis) 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.

5. Expected survival of at least 3 months. 6. According to the RECIST v1.1 criteria, there is at least one measurable lesion in the dose expansion stage.

7. The functional level of bone marrow reserve and organs must meet the following requirements (without ongoing continuous supportive treatment): Bone marrow reserve: neutrophil count (NE#) = 1.5×109/L, platelet count (PLT) = 90×109/L, and hemoglobin (HGB) > 9.0 g/dL (no blood transfusion or hematopoietic stimulating factor therapy within 14 days). Coagulation function: activated partial prothrombin time (APTT) prolonged to =1.5×ULN, and international normalized ratio (INR) =1.5. Liver function: total bilirubin (TBIL) = 1.5×ULN, and alanine aminotransferase (ALT), and aspartate aminotransferase (AST) = 2.5×ULN, if there is liver metastasis, ALT and AST = 5×ULN and TBIL= 3×ULN. Renal function: creatinine clearance = 50 mL/min or serum creatinine = 1.5×ULN. 8. Eligible Participants with fertility (male and female) must agree to use reliable contraceptive methods with their partners and have no plan to have baby during the study period and at least 6 months after the last administration. female Participants of childbearing age must have a negative serum or urine pregnancy test during screening period and before the first dose.

9. Other participants that can potentially benefit from the investigational drug as assessed by the investigator.

Exclusion Criteria:

• 1. Participants who are known to be allergic to doxorubicin and/or other similar compounds, or to any of excipients of HF158K1, or participants with allergic constitution (multiple drug and food allergies).

2. Participants who have used doxorubicin prior to screening with a total cumulative dose > 350 mg/m2 (other anthracyclines converted by 1 mg doxorubicin equivalence: 2 mg epirubicin, or 2 mg epirubicin, or 2 mg zolpidem, or 0.5 mg demethoxyzolpidem), or who have received anthracyclines and suffered severe cardiotoxicity, or who discontinued doxorubicin liposome therapy due to serious adverse events.

3. Participants who received radiotherapy or chemotherapy (paclitaxel, cyclosporine, dextropropylenol, cytarabine, streptozotocin, etc.) within 4 weeks prior to first dose administration, or received other antitumor therapy such as endocrine therapy, herbal therapy, or local radiation therapy for pain relief within 2 weeks prior to first dose administration, except for the following: Nitrosourea or mitomycin C within 6 weeks prior to the first administration of the investigational drug. Oral fluorouracil-based and small-molecule targeted drugs for 2 weeks prior to the first administration of the investigational drug or within 5 half-lives of the drug (whichever is longer).

4. Participants with brain parenchymal metastases or meningeal metastases with clinical symptoms that, in the judgment of the investigator, are not suitable for enrollment (those who have received prior treatment (radiation or surgery) for systemic, radical brain metastases, have maintained imaging- confirmed stability for at least 28 days, and have discontinued systemic steroid therapy for > 14 days without clinical symptoms will be allowed for enrollment).

5. Participants who have not recovered to < Grade 1 (according to CTCAE 5.0) or to pre-treatment baseline levels from all prior treatment-induced adverse events prior to the first dose (except for adverse events without safety risks as judged by the investigator, such as alopecia, Grade 2 peripheral neurotoxicity, and stabilized hypothyroidism under hormone replacement therapy).

6. Participants who are taking (or are not able to discontinue until at least 1 week before the first dose of the study) any drug known to strongly inhibit or strongly induce CYP3A4, CYP2D6 or P-gp.

7. Participants with a history of serious cardiovascular and cerebrovascular diseases, including but not limited to: Serious heart rhythm or conduction abnormalities, such as ventricular arrhythmia that requires clinical intervention, degree II-III atrioventricular block, etc. Cardiac function: left ventricular ejection fraction (LVEF) = 50%, corrected QT interval (QTcF) > 470 ms. Thromboembolic events requiring therapeutic anticoagulation within 3 months before the first administration, or participants with venous filters. Participants with Class III~IV cardiac insufficiency according to the New York Heart Association (NYHA) criteria. Acute coronary syndrome, congestive heart failure, aortic dissection, stroke or other Grade 3 and above cardiovascular and cerebrovascular events within 6 months before the first administration. Clinically uncontrollable hypertension (systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg), and patients with a history of hypertension were allowed to enroll as long as their blood pressure was controlled below this limitation through antihypertensive therapy. Any factors that increase the risk of QTc prolongation or arrhythmia, such as heart failure, hypokalemia, congenital long QT syndrome, or use of any concomitant drug that are known to or may prolong the QT interval.

8. Participants who have received last dose of any other investigational drug product or treatments within 28 days prior to the first administration of the investigational drug.

9. Participants who have undergone major organ surgery (excluding needle biopsy,tracheotomy, gastrostomy, etc.) or had significant trauma within 28 days before the first administration of investigational drug or need to undergo elective surgery during the study period.

10. Participants with a serious unhealable wound/ulcer/fracture within 28 days before the first administration of the investigational drug.

11. Participants with an active infection within 1 week prior to the first administration of the investigational drug and currently require intravenous anti-infection therapy.

12. Third space effusion that cannot be clinically controlled and is not suitable for enrollment as judged by the investigator.

13. Known history of drug abuse. 14. Participants with mental disorders or poor compliance.

15. HIV infection, active HBV infection (HBV DNA > ULN), or active HCV infection (HCV RNA > ULN).

16. Women who are pregnant or breastfeeding. 17. Participants who cannot tolerate venous blood sampling. 18. The investigator believes that the participant has a history of other serious systemic diseases or is not suitable for participating in this clinical study for other reasons.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumors, Adult

Intervention

Drug:
• HF158K1 /Arm 2 mg/m²
Duration of infusion: HF158K1 is diluted using 5% (50 mg/ml) glucose injection or 0.9% sodium chloride injection (saline) to a total volume of 250 ml and is administered through intravenous infusion for 90 ± 10 min.
• HF158K1 /Arm 6 mg/m²
Duration of infusion: HF158K1 is diluted using 5% (50 mg/ml) glucose injection or 0.9% sodium chloride injection (saline) to a total volume of 250 ml and is administered through intravenous infusion for 90 ± 10 min.
• HF158K1 /Arm 15 mg/m²
Duration of infusion: HF158K1 is diluted using 5% (50 mg/ml) glucose injection or 0.9% sodium chloride injection (saline) to a total volume of 250 ml and is administered through intravenous infusion for 90 ± 10 min.
• HF158K1 /Arm 30 mg/m²
Duration of infusion: HF158K1 is diluted using 5% (50 mg/ml) glucose injection or 0.9% sodium chloride injection (saline) to a total volume of 250 ml and is administered through intravenous infusion for 90 ± 10 min.
• HF158K1 /Arm 45 mg/m²
Duration of infusion: HF158K1 is diluted using 5% (50 mg/ml) glucose injection or 0.9% sodium chloride injection (saline) to a total volume of 250 ml and is administered through intravenous infusion for 90 ± 10 min.
• HF158K1 /Arm 60 mg/m²
Duration of infusion: HF158K1 is diluted using 5% (50 mg/ml) glucose injection or 0.9% sodium chloride injection (saline) to a total volume of 250 ml and is administered through intravenous infusion for 90 ± 10 min.

Locations

Country	Name	City	State
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Zhejiang Xiaoshan Hospital	Hangzhou	Zhejiang
United States	Mary Crowley Cancer Research	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
HighField Biopharmaceuticals Corporation

Countries where clinical trial is conducted

United States,  China, 

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