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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат HF50
  HF50 is a liposomal T-cell engager with an unique design based on the lipid bilayer. It was also named a T cell Redirecting Antibody Fragment-anchored Liposomes (TRAFsome). The liposomal surface carries anti-CD3ε and anti-HER2 antibody-conjugated lipid molecules, enabling T-cell redirection and activation at HER2-positive or HER2-low tumor sites. In addition, the liposome internal space contains a TLR7/8 agonist Resiquimod (R848), which has been shown to help modulate the myeloid cells in the tu

Первичные конечные точки

• Number of Participants with Dose Limiting Toxicities (DLT) [Срок оценки: 28 days after the first dose (C1D1) for each dose cohort.]
• Incidence of Adverse Events (AEs) [Срок оценки: From first dose to 28 days after the last dose.]
• Incidence of Serious Adverse Events (SAEs) [Срок оценки: From first dose to 28 days after the last dose.]
• Recommended Phase II Dose (RP2D) of HF50 [Срок оценки: At the end of dose escalation (assessed up to 1 year)]
• Incidence of Vital Sign Abnormalities [Срок оценки: From first dose to the end of the study (assessed up to 1 year)]
• Laboratory Abnormalities [Срок оценки: From first dose to the end of the study (assessed up to 1 year)]
• Incidence of Electrocardiogram (ECG) Abnormalities [Срок оценки: From first dose to the end of the study (assessed up to 1 year)]
• Incidence of Echocardiography (ECHO) Abnormalities [Срок оценки: From first dose to the end of the study (assessed up to 1 year)]

Вторичные конечные точки (9)

• Pharmacokinetic Parameter - Cmax [Срок оценки: Up to 9 weeks]
• Pharmacokinetic Parameter - Tmax [Срок оценки: Up to 9 weeks]
• Pharmacokinetic Parameter - AUC (Area Under the Curve) [Срок оценки: Up to 9 weeks]
• Pharmacokinetic Parameter - Half-life (t1/2) [Срок оценки: Up to 9 weeks]
• Objective Response Rate (ORR) [Срок оценки: Up to 2 years]
• Duration of Response (DOR) [Срок оценки: Up to 2 years]
• Disease Control Rate (DCR) [Срок оценки: Up to 2 years]
• Progression-Free Survival (PFS) [Срок оценки: Up to 2 years]
• Overall Survival (OS) [Срок оценки: Up to 2 years]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• West China Hospital of Sichuan University — Чэнду

Идентификаторы

NCT: NCT06822998 · HF50-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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