HF50 in HER-2 Positive and Low-expression Advanced Solid Tumors

An Open-label, Single-arm, Non-randomized, Single-center, Dose-escalation Study to Evaluate the Safety, Tolerability, and Preliminary Antitumor Activity of HF50 in Subjects With HER-2 Positive and HER-2 Low-expression Advanced Solid Tumors

This is an open-label, single-arm, non-randomized, single-center, dose-escalation study designed to evaluate the safety and tolerability of HF50 in patients with HER-2 positive and HER-2 low-expression advanced solid tumors. The primary objectives are to assess the safety, tolerability, and determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of HF50. Secondary objectives include evaluating the pharmacokinetic (PK) profile and preliminary antitumor activity of HF50.

Inclusion Criteria:

• Participants must voluntarily provide written informed consent (ICF) prior to any study-related procedures, and be capable of complying with all protocol requirements.
• Adult participants aged between 18 and 75 years (inclusive) at the time of ICF signing.
• Histologically or cytologically confirmed advanced HER-2 positive or HER-2 low-expression solid tumors that are unresectable, metastatic, or have relapsed after standard therapies, are intolerant to standard therapies (e.g., chemotherapy, targeted therapy), or lack effective treatment options.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy of at least 3 months.
• At least one measurable lesion as defined by RECIST version 1.1.
• Adequate organ and bone marrow function as demonstrated by the following laboratory parameters:Hematologic Function:Absolute neutrophil count (ANC) ≥1.5×10⁹/L、Lymphocyte count ≥1.0×10⁹/L、Platelet count ≥90×10⁹/L、Hemoglobin ≥9.0 g/dL (without transfusion or erythropoietin-stimulating agents within 14 days)； Coagulation Parameters:Activated partial thromboplastin time (aPTT) ≤1.5×ULN、 International normalized ratio (INR) ≤1.5. Hepatic Function:Total bilirubin (TBIL) ≤1.5×ULN、Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN (≤5×ULN for participants with liver metastases, and TBIL ≤3×ULN)； Renal Function:Creatinine clearance (CrCl) ≥50 mL/min (Cockcroft-Gault formula).
• Female participants of childbearing potential must have a negative serum pregnancy test at screening and prior to the first dose. Male and female participants of childbearing potential must agree to use effective contraception during the study and for 6 months after the last dose.

Exclusion Criteria:

• History of active autoimmune disease or autoimmune disease considered unsuitable for study participation, with exceptions for localized skin conditions (e.g., eczema involving <10% of body surface area, vitiligo, psoriasis, alopecia) or childhood asthma resolved without treatment in adulthood.
• Current use of immunosuppressants or systemic corticosteroids (>10 mg/day prednisone or equivalent) within 4 weeks prior to the first dose, except for local steroid use.
• Receipt of systemic chemotherapy, radiotherapy, targeted therapy, or immunotherapy less than 2 weeks (or 4 weeks for nitrosourea or mitomycin C) or within 5 half-lives of the prior therapy before the first dose.
• Symptomatic brain metastases or leptomeningeal disease unless adequately treated (e.g., surgery or radiotherapy) with no evidence of progression for ≥28 days and off systemic steroids for ≥14 days prior to the first dose.
• Unresolved toxicities from prior therapies ≥Grade 2 (CTCAE v5.0) at baseline, except for toxicities deemed by the investigator to pose no safety risk (e.g., alopecia, stable hypothyroidism with hormone replacement).
• Significant cardiovascular or cerebrovascular conditions, including but not limited to:Thromboembolic events requiring therapeutic anticoagulation within 3 months prior to the first dose.NYHA Class III or IV heart failure.Acute coronary syndrome, congestive heart failure, aortic dissection, or stroke within 6 months prior to the first dose.Uncontrolled hypertension (systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg), unless controlled with antihypertensive medication.
• Active infection or unexplained fever >38.5°C within 1 week prior to the first dose (tumor-related fever may be eligible at the investigator's discretion).
• Known HIV infection, active hepatitis B virus (HBV) infection (HBV DNA >ULN), or active hepatitis C virus (HCV) infection (HCV RNA >ULN).
• Gastrointestinal symptoms or other conditions requiring intervention within 4 weeks prior to the first dose that would, in the investigator's judgment, impair study participation.
• Pregnant or breastfeeding women.
• Any other severe systemic disease, psychological condition, or significant clinical abnormality deemed unsuitable for study participation by the investigator.