Safety and Activity of HF50 in Patients With Advanced Solid Tumors

A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-tumor Activity of HF50 in Patients With Advanced Solid Tumors

A study to assess the safety, tolerability, and pharmacokinetics of HF50 in participants with advanced solid tumors.

This is an open-label, dose-escalation and dose-expansion, multiple-dose, phase 1 study evaluating HF50 monotherapy in participants with advanced solid tumors. HF50 is an innovative liposome-encapsulated T-cell engager designed to redirect T-cells to tumor cells by presenting both tumor-associated antigen (e.g., HER2) and CD3 targeting moieties on the liposome surface. Simultaneously, HF50 delivers an encapsulated TLR7/8 agonist to activate innate immunity and remodel the tumor immune microenvironment, creating a synergistic anti-tumor immune response.The primary objective is to evaluate the safety and tolerability of HF50 and to determine the recommended Phase 2 dose (RP2D). HF50 will be administered as an intravenous (IV) infusion. The study will also assess the pharmacokinetic (PK) profile, immunogenicity, and preliminary anti-tumor activity of HF50. Additionally, the study will explore the impact of HF50 on the immune microenvironment and changes in peripheral blood cytokines and immune cells to better understand its biological effects.

Inclusion Criteria:

• Voluntary participation: Capable of giving signed informed consent and able to comply with all study-related procedures.
• Age: Adults >= 18 years of age at the time of signing informed consent; male or female.
• Disease Status: Participants with histologically or cytologically confirmed advanced solid tumors that are unresectable or metastatic, who have failed or are intolerant to standard therapies, or for whom no effective therapy currently exists. Examples include HER2-expressing gynecological tumors and recurrent ovarian clear cell carcinoma after failure of platinum-based chemotherapy.
• Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1.
• Life Expectancy: Anticipated survival of no less than 6 months.
• Measurable Disease: At least one measurable lesion according to RECIST v1.1 definitions.
• Organ and Bone Marrow Function:

Bone Marrow Reserve: Absolute neutrophil count (ANC) >= 1.5 x 10^9/L, lymphocyte count >= 1.0 x 10^9/L, platelet count >= 90 x 10^9/L, and hemoglobin >= 9.0 g/dL (no blood transfusion or hematopoietic stimulators within 14 days).

Coagulation Function: Activated partial thromboplastin time (APTT) <= 1.5 x ULN, and International Normalized Ratio (INR) <= 1.5.

Liver Function: Total bilirubin (TBIL) <= 1.5 x ULN, and ALT and AST <= 2.5 x ULN. For participants with liver metastases: ALT and AST <= 5 x ULN, and TBIL <= 3 x ULN.

Renal Function: Creatinine clearance >= 50 mL/min (calculated using the Cockcroft-Gault formula).

• Contraception: Participants of reproductive potential (including males) must agree to use effective contraception from study entry through 6 months after the last dose. Female participants of childbearing potential must have a negative serum pregnancy test during screening and prior to the first dose.

Exclusion Criteria:

• Autoimmune Disease: Any active autoimmune disease or history of autoimmune disease deemed unsuitable by the investigator. Exceptions include skin conditions not requiring systemic treatment (e.g., eczema < 10% of body surface area, vitiligo, psoriasis, alopecia) and resolved childhood asthma.
• Corticosteroids/Immunosuppressants: Current use of immunosuppressants or systemic corticosteroids (> 10 mg/day prednisone or equivalent) within 4 weeks prior to the first dose. Topical steroid use is permitted.
• Prior Anti-tumor Therapy: Receipt of systemic chemotherapy, radiotherapy, targeted therapy, or immunotherapy within 2 weeks prior to dosing (4 weeks for nitrosoureas or mitomycin C); or other therapies (endocrine therapy, TCM, localized palliative radiotherapy) within 2 weeks.
• CNS Metastasis: Clinically symptomatic brain or meningeal metastases. Participants with treated brain metastases are eligible if radiographic stability is maintained for >= 28 days, systemic steroids have been discontinued for > 14 days, and the participant is asymptomatic.
• Toxicity Recovery: Failure to recover from all adverse events of prior therapies to <= Grade 1 (NCI CTCAE v5.0) or baseline, except for alopecia, Grade 2 peripheral neuropathy, or stable hypothyroidism on hormone replacement.
• Cardiovascular History: Including thromboembolic events within 3 months; NYHA Class III to IV congestive heart failure; acute coronary syndrome, aortic dissection, stroke, or other Grade >= 3 cardiovascular events within 6 months; or uncontrolled hypertension (SBP > 160 mmHg or DBP > 100 mmHg).
• Infection: Active infection or unexplained fever > 38.5 degrees C within 1 week prior to the first dose (tumor-related fever is permitted per investigator judgment).
• Viral Infection: HIV infection, active HBV (HBV DNA > ULN), or active HCV (HCV RNA > ULN).
• Gastrointestinal Symptoms: Significant digestive system symptoms or other factors requiring intervention within 4 weeks prior to the first dose.
• Pregnancy/Lactation: Female participants who are pregnant or breastfeeding.
• Other: Any other serious systemic disease or reason that, in the investigator's opinion, makes the participant unsuitable for the study.