HF50 in HER-2 Positive and Low-expression Advanced Solid... | NCT06822998

NCT06822998

Protocol Section

Identification Module

Results Section

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Annotation Section

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Document Section

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No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Dose Level 1 - 1 mg	Experimental	Participants in this arm will receive HF50 via intravenous infusion once weekly for 3 weeks in a 3-week treatment cycle. The dose is 1 mg, with a lead-in dose on Cycle 1 Day 1 (C1D1) followed by the target dose on C1D8, C1D15, and C1D22.	Drug: HF50
Dose Level 2 - 10 mg	Experimental	Participants in this arm will receive HF50 via intravenous infusion once weekly for 3 weeks in a 3-week treatment cycle. The dose is 10 mg, with a lead-in dose on C1D1 followed by the target dose on C1D8, C1D15, and C1D22.	Drug: HF50
Dose Level 3 - 60 mg	Experimental	Participants in this arm will receive HF50 via intravenous infusion once weekly for 3 weeks in a 3-week treatment cycle. The dose is 60 mg, with a lead-in dose on C1D1 followed by the target dose on C1D8, C1D15, and C1D22.	Drug: HF50
Dose Level 4 - 240 mg	Experimental	Participants in this arm will receive HF50 via intravenous infusion once weekly for 3 weeks in a 3-week treatment cycle. The dose is 240 mg, with a lead-in dose on C1D1 followed by the target dose on C1D8, C1D15, and C1D22.	Drug: HF50

Interventions

Name	Type	Description	Arm Group Labels	Other Names
HF50	Drug	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 tumor micro-environement to complement the immune activation effects.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants with Dose Limiting Toxicities (DLT)	The number of participants experiencing dose-limiting toxicities (DLTs) during the DLT evaluation period to determine the maximum tolerated dose (MTD).	28 days after the first dose (C1D1) for each dose cohort.
Incidence of Adverse Events (AEs)	The number and percentage of participants experiencing adverse events (AEs), graded according to NCI-CTCAE v5.0	From first dose to 28 days after the last dose.
Incidence of Serious Adverse Events (SAEs)	The number and percentage of participants experiencing adverse events (AEs), graded according to NCI-CTCAE v5.0.	From first dose to 28 days after the last dose.
Recommended Phase II Dose (RP2D) of HF50	RP2D will be determined based on safety, tolerability, and pharmacokinetics data collected during the dose escalation phase.	At the end of dose escalation (assessed up to 1 year)
Incidence of Vital Sign Abnormalities	Number of participants who experienced a maximum severity of Grade 3 or higher post-baseline vital sign abnormality, including blood pressure, heart rate, respiratory rate, and body temperature. Grades are defined using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.	From first dose to the end of the study (assessed up to 1 year)
Laboratory Abnormalities	Number of participants who experienced a maximum severity of Grade 3 or higher post-baseline laboratory abnormality, including hematology (complete blood count), blood chemistry, urinalysis, coagulation function, and C-reactive protein (CRP). Grades are defined using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.

Secondary Outcomes

Measure	Description	Time Frame
Pharmacokinetic Parameter - Cmax	Maximum plasma concentration (Cmax) of HF50 will be assessed following single and multiple dosing.	Up to 9 weeks
Pharmacokinetic Parameter - Tmax	Time to maximum plasma concentration (Tmax) of HF50 will be assessed following single and multiple dosing.

Eligibility Module

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.