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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose escalation: HF158K1 1.4 g lipid dose | Experimental | 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. |
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| Dose escalation: HF158K1 2.2 g lipid dose | Experimental | 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. |
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| Dose escalation: HF158K1 2.9 g lipid dose | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HF158K1 / 1.4 g lipid dose | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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). |
| 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） |
| Red blood cell count in whole blood sample | Changes from baseline for Red blood cell count in whole blood | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| White blood cell in whole blood sample | Changes from baseline for white blood cell count in whole blood | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Hematocrit in whole blood sample | Changes from baseline for Hematocrit in whole blood | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Neutrophil count in whole blood sample | Changes from baseline for neutrophil count in whole blood | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Measure | Description | Time Frame |
|---|---|---|
| HF158K1 pharmacokinetic parameters with Cmax | Maximum plasma concentration (Cmax) after administration of HF158K1 | Within 336 hours after the first and second administration |
| AUC by plasma concentration of whole blood sample |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| MINAL BARVE | Mary Crowley Cancer Research | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mary Crowley Cancer Research | Recruiting | Dallas | Texas | 75241 | United States |
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| HF158K1 / 2.2 g lipid dose | Drug | 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. |
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| HF158K1 / 2.9 g lipid dose | Drug | 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. |
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| Hemoglobin concentration in whole blood sample | Changes from baseline for hemoglobin concentration in whole blood | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Percentage of lymphocytes (LYM%) | Changes from baseline for Percentage of lymphocytes (LYM%) in whole blood | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Lymphocyte count | Changes from baseline for Lymphocyte count in whole blood | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Percentage of neutrophils (NEU%) Percentage of neutrophils (NEU%) | Changes from baseline for Percentage of neutrophils (NEU%) in whole blood | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Platelet count in whole blood sample | Changes from baseline for Platelet count in whole blood | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Prothrombin time in whole blood sample | Changes from baseline for Prothrombin time in whole blood sample | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| International normalized ratio in whole blood sample | Changes from baseline for international standardized ratio in whole blood sample | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Fibrinogen in whole blood sample | Changes from baseline for Fibrinogen in whole blood | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Activated partial prothrombin time in whole blood sample | Changes from baseline for activated partial thromboplastin time in whole blood sample | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Total bilirubin concentration in whole blood sample | Changes from baseline for total bilirubin concentration in whole blood sample | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| ALT concentration in whole blood sample | Changes from baseline for alanine aminotransferase(ALT) concentration in whole blood sample | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| AST concentration in whole blood sample | Changes from baseline for aspartate aminotransferase(AST) concentration in whole blood sample | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Total protein concentration in whole blood sample | Changes from baseline for total protein concentration in whole blood sample | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Urea concentration in whole blood sample | Changes from baseline for urea concentration in whole blood sample | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Creatinine concentration in whole blood sample | Changes from baseline for creatinine concentration in whole blood sample | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Total cholesterol concentration in whole blood sample | Changes from baseline for total cholesterol concentration in whole blood sample | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Triglycerides concentration in whole blood sample | Changes from baseline for triglycerides concentration in whole blood sample | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| HDL-C in whole blood sample | Changes from baseline for high density lipoprotein cholesterol (HDL-C) in whole blood sample | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| LDL-C in whole blood sample | Changes from baseline for low density lipoprotein cholesterol (LDL-C) in whole blood sample | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Glucose in whole blood sample | Changes from baseline for Lactic dehydrogenase in whole blood | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Alkaline phosphatase in whole blood sample | Changes from baseline for Lactic dehydrogenase in whole blood | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Lactic dehydrogenase in whole blood sample | Changes from baseline for Lactic dehydrogenase in whole blood | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Gamma-glutamyl transferase in whole blood sample | Changes from baseline for Gamma-glutamyl transferase in whole blood | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Albumin in whole blood sample | Changes from baseline for Albumin in whole blood | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Direct bilirubin in whole blood sample | Changes from baseline for Direct bilirubin in whole blood | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Sodium in whole blood sample | Changes from baseline for Sodium in whole blood | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Potassium in whole blood sample | Changes from baseline for Potassium in whole blood | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Chloride in whole blood sample | Changes from baseline for Chloride in whole blood | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Calcium in whole blood sample | Changes from baseline for Calcium in whole blood | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Phosphate in whole blood sample | Changes from baseline for Phosphate in whole blood | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Uric acid in whole blood sample | Changes from baseline for Uric acid in whole blood | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Creatine kinase in whole blood sample | Changes from baseline for Creatine kinase in whole blood | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Creatine kinase isoenzyme in whole blood sample | Changes from baseline for Creatine kinase isoenzyme in whole blood | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Troponin-T (TnT) in whole blood sample | Changes from baseline for Troponin-T in whole blood | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Troponin-I (TnI) in whole blood sample | Changes from baseline for Troponin-I in whole blood | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Urine protein in urine sample | Changes from baseline for Urine protein in urine sample | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Red blood cells in urine sample | Changes from baseline for Red blood cells in urine sample | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| White blood cells in urine sample | Changes from baseline for White blood cells in urine sample | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| PH in urine sample | Changes from baseline for pH in urine sample | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Ketone bodies in urine sample | Changes from baseline for Ketone bodies in urine sample | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Urine glucose in urine sample | Changes from baseline for Urine glucose in urine sample | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Urine bilirubin in urine sample | Changes from baseline for Urine bilirubin in urine sample | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Urine occult blood in urine sample | Changes from baseline for Urine occult blood in urine sample | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Heart Rate in beats per minute in beats per minute of ECG | Changes from baseline for heart rate in beats per minute | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| RR Interval by ECG | Changes from baseline for RR interval by ECG | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| PR Interval by ECG | Changes from baseline for PR interval by ECG | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| QRS Interval by ECG | Changes from baseline for QRS interval by ECG | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| QT Interval by ECG | Changes from baseline for QT interval by ECG | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| QTcF by ECG | Changes from baseline for QTcF interval by ECG | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Left ventricular ejection fraction measured by Echocardiography | Changes from baseline for Left ventricular ejection fraction measured by Echocardiography | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Body (Ear) Temperature measurement in Vital Signs | Changes from baseline for Body (Ear) Temperature | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Pulse measurement in Vital Signs | Changes from baseline for Pulse | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Respiration Rate measurement in Vital Signs | Changes from baseline for respiration rate in breaths of Vital Signs | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Sitting Systolic Blood Pressure | Changes from baseline for Sitting Systolic Blood Pressure | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| Sitting Diastolic Blood Pressure | Changes from baseline for Sitting Diastolic Blood Pressure | Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year) |
| 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 Ic） |
| 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. |
Area under plasma concentration -time curve after dose
| Within 336 hours after the first and second administration |
| Tmax by plasma concentration of whole blood sample | Peak time (Tmax) after dose | Within 336 hours after the first and second administration |
| 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 |
| CL by plasma concentration of whole blood sample | Clearance (CL) after dose | Within 336 hours after the first and second administration |
| Vd by plasma concentration of whole blood sample | Volume of distribution(Vd) after dose | Within 336 hours after the first and second administration |
| 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 |
| 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. |
| 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. |
| 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. |
| 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 |
| Sun Yat-sen University Cancer Center | Recruiting | Guangzhou | Guangdong | 510060 | China |
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