HF158K1 in Patients With HER-2 Expressing Advanced Solid Tumors

NCT05861895 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: HF158K1-101
• Study Type: interventional
• Target: 84
• Locations: 2 countries
• Sites: 2

Brief 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.

Conditions

Solid Tumors, Adult

Outcome Measures

Primary Outcomes (63)

• 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)

• 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.

Secondary Outcomes (11)

• HF158K1 pharmacokinetic parameters with Cmax

  Within 336 hours after the first and second administration

• AUC by plasma concentration of whole blood sample

  Within 336 hours after the first and second administration

• Tmax by plasma concentration of whole blood sample

  Within 336 hours after the first and second administration

• T1/2 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

Study Arms (3)

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.

Drug: HF158K1 / 1.4 g lipid dose

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.

Drug: HF158K1 / 2.2 g lipid dose

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.

Drug: HF158K1 / 2.9 g lipid dose

Interventions

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.

Also known as: Infusion

Dose escalation: HF158K1 2.9 g lipid dose

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.

Also known as: Infusion

Dose escalation: HF158K1 2.2 g lipid dose

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.

Also known as: Infusion

Dose escalation: HF158K1 1.4 g lipid dose

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 0-1.
• Expected survival ≥ 6 months.
• At least one measurable lesion per RECIST v1.1.
• 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.

You may not qualify if:

• 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 1.
• 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.

Sponsors & Collaborators

• HighField Biopharmaceuticals Corporation: lead

Study Sites (2)

Mary Crowley Cancer Research

Dallas, Texas, 75241, United States

RECRUITING

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Study Officials

• MINAL BARVE

  Mary Crowley Cancer Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2023
• First Posted: May 17, 2023
• Study Start: December 12, 2023
• Primary Completion (Estimated): June 23, 2027
• Study Completion (Estimated): December 23, 2027
• Last Updated: June 26, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); CN (1)