HF158K1 in Patients With HER-2 Expressing Advanced Solid Tumors

Official 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

Overview

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.

Detailed 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 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.

Interventions

• Drug HF158K1 / 1.4 g lipid dose
  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.
• Drug HF158K1 / 2.2 g lipid dose
  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.
• Drug HF158K1 / 2.9 g lipid dose
  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.

Primary outcome measures

• 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).]
• 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）]
• 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)]
• 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)]
• 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)]
• 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)]
• 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)]
• 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)]
• Lymphocyte count [Time frame: 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%) [Time frame: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)]

Secondary outcome measures (11)

• HF158K1 pharmacokinetic parameters with Cmax [Time frame: Within 336 hours after the first and second administration]
• AUC by plasma concentration of whole blood sample [Time frame: Within 336 hours after the first and second administration]
• Tmax by plasma concentration of whole blood sample [Time frame: Within 336 hours after the first and second administration]
• T1/2 by plasma concentration of whole blood sample [Time frame: Within 336 hours after the first and second administration]
• CL by plasma concentration of whole blood sample [Time frame: Within 336 hours after the first and second administration]
• Vd by plasma concentration of whole blood sample [Time frame: Within 336 hours after the first and second administration]
• AUClast by plasma concentration of whole blood sample [Time frame: Within 336 hours after the first and second administration]
• 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.]
• 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.]
• 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.]
• 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]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Mary Crowley Cancer Research — Dallas

China · 1 center

• Sun Yat-sen University Cancer Center — Guangzhou

Identifiers

NCT: NCT05861895 · HF158K1-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗