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Background HF50 is a novel liposomal T-cell engager (TCE) engineered to anchor both anti-CD3ε and anti-HER2 fragments on the surface for interacting with T-cell and encapsulate a TLR7/8 agonist for activating myeloid cells for complementary immune stimulation. Preclinical data suggest a wider therapeutic window and a reduced risk of cytokine release syndrome (CRS) compared to traditional TCEs. This study aims to evaluate the safety and preliminary efficacy of HF50.Methods This is a first-in-human, open-label, Phase I dose-escalation study ( NCT06822998) designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor efficacy of HF50. The trial enrolls patients with advanced HER2-positive or HER2-low (IHC ≥ 1+) solid tumors who have failed, are intolerant to, or lack effective standard treatment options. We utilize a weekly intravenous infusion schedule that incorporates a step-up dosing regimen to mitigate potential CRS.Results As of September 15, 2025, 4 patients with relapsed or metastatic salivary gland cancer (comprising 3 with salivary duct carcinoma [SDC] and 1 with adenoid cystic carcinoma [AdCC]) were enrolled and had received HF-50 across three dose levels, among which 1 patient at the dose of 1 mg, 1 patient at the dose of 10 mg, and 2 patients at the dose of 60 mg.Safety Treatment-related adverse events (TRAEs) were reported in all 4 patients. Patient 1 experienced transient Grade 1 discomfort in the cervical lymph node region. Patient 2 developed a Grade 1 blister at the tumor site and experienced persistent site discharge. Patient 3 experienced Grade 1 CRS (fever), which resolved within 24 hours following acetaminophen. Patient 4 reported Grade 1 rash. No dose-limited toxicity (DLT) was observed.Efficacy As of the abstract submission date, three of the four patients remained on treatment, one achieved PR; one had PD; and two are awaiting efficacy assessment. Serial immune monitoring of patient PBMCs showed that CD3 + T cells exhibited increasing IL-2 IFN-γ, and IL-6 production and reduced IL-4/IL-10, consistent with a sustained effector phenotype and no evidence of exhaustion. Additional longitudinal data from other patients are being collected to define cytokine profile changes associated with clinical response.Conclusions HF-50 demonstrated a manageable safety profile and was well-tolerated at the tested dose levels in this cohort. Preliminary anti-tumor activity was observed, evidenced by a ORR of 50% and tumor shrinkage at a low dose level (1 mg) in a pretreated SDC patient. These findings support continued dose escalation and further investigation of HF-50 in this population.Trial Registration NCT06822998Ethics Approval The Ethical Committee for Research in Human Subjects of West China Hospital approved the study (2025-706). All participants gave informed consent before taking part.Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.