HF158K1 in Patients With HER-2 Expressing Advanced Solid Tumors

A Phase 1 Clinical Study to Investigate the Safety, Tolerability, and Preliminary Efficacy of HF158K1 in Participants 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.

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.

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.