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NCT Number: NCT05861895

HF158K1 in Patients With HER-2 Expressing Advanced Solid Tumors

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.

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Key information

Conditions

Solid Tumors, Adult

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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.

Treatment and study plan

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.

Other names: Infusion

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.

Other names: Infusion

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.

Other names: Infusion

Primary outcomes

  1. Incidence of Adverse Events

    Time frame: 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)

  2. Incidence of dose-limiting toxicities(DLT)

    Time frame: 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

  3. Red blood cell count in whole blood sample

    Time frame: 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

  4. White blood cell in whole blood sample

    Time frame: 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

  5. Hematocrit in whole blood sample

    Time frame: 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

  6. Neutrophil count in whole blood sample

    Time frame: 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

  7. Hemoglobin concentration in whole blood sample

    Time frame: 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

  8. Percentage of lymphocytes (LYM%)

    Time frame: 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

  9. Lymphocyte count

    Time frame: 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

  10. Percentage of neutrophils (NEU%) Percentage of neutrophils (NEU%)

    Time frame: 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

  11. Platelet count in whole blood sample

    Time frame: 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

  12. Prothrombin time in whole blood sample

    Time frame: 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

  13. International normalized ratio in whole blood sample

    Time frame: 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

  14. Fibrinogen in whole blood sample

    Time frame: 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

  15. Activated partial prothrombin time in whole blood sample

    Time frame: 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

  16. Total bilirubin concentration in whole blood sample

    Time frame: 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

  17. ALT concentration in whole blood sample

    Time frame: 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

  18. AST concentration in whole blood sample

    Time frame: 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

  19. Total protein concentration in whole blood sample

    Time frame: 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

  20. Urea concentration in whole blood sample

    Time frame: 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

  21. Creatinine concentration in whole blood sample

    Time frame: 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

  22. Total cholesterol concentration in whole blood sample

    Time frame: 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

  23. Triglycerides concentration in whole blood sample

    Time frame: 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

  24. HDL-C in whole blood sample

    Time frame: 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

  25. LDL-C in whole blood sample

    Time frame: 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

  26. Glucose in whole blood sample

    Time frame: 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

  27. Alkaline phosphatase in whole blood sample

    Time frame: 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

  28. Lactic dehydrogenase in whole blood sample

    Time frame: 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

  29. Gamma-glutamyl transferase in whole blood sample

    Time frame: 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

  30. Albumin in whole blood sample

    Time frame: 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

  31. Direct bilirubin in whole blood sample

    Time frame: 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

  32. Sodium in whole blood sample

    Time frame: 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

  33. Potassium in whole blood sample

    Time frame: 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

  34. Chloride in whole blood sample

    Time frame: 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

  35. Calcium in whole blood sample

    Time frame: 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

  36. Phosphate in whole blood sample

    Time frame: 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

  37. Uric acid in whole blood sample

    Time frame: 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

  38. Creatine kinase in whole blood sample

    Time frame: 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

  39. Creatine kinase isoenzyme in whole blood sample

    Time frame: 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

  40. Troponin-T (TnT) in whole blood sample

    Time frame: 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

  41. Troponin-I (TnI) in whole blood sample

    Time frame: 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

  42. Urine protein in urine sample

    Time frame: 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

  43. Red blood cells in urine sample

    Time frame: 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

  44. White blood cells in urine sample

    Time frame: 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

  45. PH in urine sample

    Time frame: 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

  46. Ketone bodies in urine sample

    Time frame: 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

  47. Urine glucose in urine sample

    Time frame: 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

  48. Urine bilirubin in urine sample

    Time frame: 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

  49. Urine occult blood in urine sample

    Time frame: 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

  50. Heart Rate in beats per minute in beats per minute of ECG

    Time frame: 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

  51. RR Interval by ECG

    Time frame: 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

  52. PR Interval by ECG

    Time frame: 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

  53. QRS Interval by ECG

    Time frame: 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

  54. QT Interval by ECG

    Time frame: 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

  55. QTcF by ECG

    Time frame: 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

  56. Left ventricular ejection fraction measured by Echocardiography

    Time frame: 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

  57. Body (Ear) Temperature measurement in Vital Signs

    Time frame: 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

  58. Pulse measurement in Vital Signs

    Time frame: 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

  59. Respiration Rate measurement in Vital Signs

    Time frame: 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

  60. Sitting Systolic Blood Pressure

    Time frame: 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

  61. Sitting Diastolic Blood Pressure

    Time frame: 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

  62. The recommended Phase II dose

    Time frame: 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.

  63. Determine the maximum tolerated dose

    Time frame: 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%).

Secondary outcomes

  1. HF158K1 pharmacokinetic parameters with Cmax

    Time frame: Within 336 hours after the first and second administration

    Maximum plasma concentration (Cmax) after administration of HF158K1

  2. AUC by plasma concentration of whole blood sample

    Time frame: Within 336 hours after the first and second administration

    Area under plasma concentration -time curve after dose

  3. Tmax by plasma concentration of whole blood sample

    Time frame: Within 336 hours after the first and second administration

    Peak time (Tmax) after dose

  4. T1/2 by plasma concentration of whole blood sample

    Time frame: Within 336 hours after the first and second administration

    Elimination half-life (T1/2) after dose

  5. CL by plasma concentration of whole blood sample

    Time frame: Within 336 hours after the first and second administration

    Clearance (CL) after dose

  6. Vd by plasma concentration of whole blood sample

    Time frame: Within 336 hours after the first and second administration

    Volume of distribution(Vd) after dose

  7. AUClast by plasma concentration of whole blood sample

    Time frame: Within 336 hours after the first and second administration

    Ratios of geometric means of AUClast (Area under the plasma concentration-time curve from zero to time of last quantifiable concentration) after dose

  8. The objective response rate(ORR) of HF158K1

    Time frame: 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.

    ORR is defined as the proportion of participants with complete response or partial response (CR+PR)

  9. disease control rate (DCR) of HF158K1

    Time frame: 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.

    DCR is defined as the proportion of participants with complete response stable disease and partial response (CR+PR+SD)

  10. duration of response(DOR) of HF158K1

    Time frame: 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.

    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.

  11. Analysis of immunogenicity

    Time frame: On the first day of the first cycle, on the first day of the fourth cycle, on the 21st day of the eighth cycle

    Immunogenicity analyses related to anti-TL01 antibody will be performed based on IMS(Immunogenicity Analysis Set).

Sponsors and collaborators

Lead sponsor

HighField Biopharmaceuticals Corporation

Industry

Registry information

Official study title

A Phase 1 Clinical Study to Investigate the Safety, Tolerability, and Preliminary Efficacy of HF158K1 in Participants With HER-2 Expressing Advanced Solid Tumors

Important dates

Study start
2023
Primary completion
2027
Study completion
2027
First posted
May 17, 2023
Registry last updated
Jun 26, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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