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

Official title

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

Overview

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.

Interventions

• Drug 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

Primary outcome measures

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

Secondary outcome measures (9)

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

Eligibility criteria

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.

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

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• West China Hospital of Sichuan University — Chengdu

Identifiers

NCT: NCT06822998 · HF50-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗