HF158K1 in Patients With HER-2 Expressing Advanced Solid Tumors

Phase 1RecruitingNCT05861895

HighField Biopharmaceuticals Corporation84 enrolled

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Solid Tumors, Adult

Interventions

HF158K1 / 1.4 g lipid doseDRUG

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 / 2.2 g lipid doseDRUG

HF158K1 / 2.9 g lipid doseDRUG

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Voluntary to participate and sign ICF. 2. Age ≥ 18 and ≤ 75 years. 3. Unresectable or metastatic advanced solid tumors with HER-2 expression (IHC 3+, 2+, or 1+). 4. ECOG score 0-1. 5. Expected survival ≥ 6 months. 6. At least one measurable lesion per RECIST v1.1. 7. 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%. 8. Agreement to use effective contraception. Exclusion Criteria: 1. Cumulative doxorubicin dose ≥ 350 mg/m² or prior anthracycline-induced cardiotoxicity. 2. Current use of immunosuppressants or systemic corticosteroids (\> 10 mg/day prednisone). 3. Prior anti-tumor therapy \< 2 weeks (4 weeks for nitrosourea/mitomycin C). 4. Symptomatic CNS metastases. 5. Unresolved AEs from prior therapy \> Grade 1. 6. Serious cardiovascular diseases (thromboembolic events within 3 months, NYHA III-IV, ACS within 6 months, or uncontrolled hypertension). 7. Active infection or unexplained fever \> 38.5°C. 8. HIV, active HBV or HCV. 9. Pregnant or breastfeeding.

Locations (2)

Mary Crowley Cancer Research

Dallas, Texas, United States

RECRUITING

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

RECRUITING

Outcomes

Primary Outcomes

Incidence of Adverse Events

Defined by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE V5.0)

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)

Observe the dose limiting toxicity, and Incidence of dose-limiting toxicities(DLT) will be assessed

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

Changes from baseline for Red blood cell count in whole blood