A Study of HF1K16 Combined With Bevacizumab in Patients With Recurrent or Progressive Glioma

A Multicenter, Open-Label, Adaptive Phase Ⅱ Clinical Study of HF1K16 Combined With Bevacizumab in Recurrent or Progressive Glioma

The primary purpose of this Phase II study is to evaluate the preliminary anti-tumor efficacy of HF1K16 in combination with Bevacizumab in patients with recurrent or progressive glioma. The study also evaluates the safety and tolerability of the combination therapy.

This multicenter, open-label, adaptive Phase II study evaluates the combination of HF1K16 and Bevacizumab in recurrent or progressive glioma. HF1K16 combines a lipid bilayer structure with all-trans retinoic acid (ATRA). In glioma patients, myeloid-derived suppressor cells (MDSCs) typically accumulate and exert strong immunosuppressive activity. HF1K16 is designed to induce immature MDSCs to differentiate into mature, active immune cells, thereby reversing immune suppression in the tumor microenvironment. The combination of HF1K16 and Bevacizumab is expected to achieve a synergistic anti-tumor effect by simultaneously inhibiting angiogenesis and remodeling the immunosuppressive tumor microenvironment to maximize efficacy.

Inclusion Criteria:

1. The patient and/or guardian must voluntarily sign and date a written informed consent form.

2. Age ≥ 18 years and ≤ 75 years at the time of informed consent signing, male or female.

3. Confirmed diagnosis of glioma by histopathology and molecular pathology, with recurrent or progressive disease following prior therapy, and no available standard treatment or intolerance to standard treatment.

4. Expected survival time of at least 3 months.

5. Karnofsky Performance Status (KPS) score ≥ 60.

6. Adequate organ and bone marrow function as defined by the following criteria:

   • Bone marrow reserve: absolute neutrophil count ≥ 1.5×10⁹/L, platelet count ≥ 90×10⁹/L, and hemoglobin ≥ 9.0 g/dL (without transfusion or hematopoietic growth factor support within 14 days);
   • Coagulation function: activated partial thromboplastin time (APTT) ≤ 1.5×ULN, and international normalized ratio (INR) ≤ 1.5×ULN;
   • Hepatic function: total bilirubin (TBIL) ≤ 1.5×ULN, and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN; in the presence of liver metastases, ALT and AST ≤ 5×ULN and TBIL ≤ 3×ULN;
   • Renal function: creatinine clearance ≥ 60 mL/min (calculated using the Cockcroft-Gault formula);
   • Left ventricular ejection fraction (LVEF) ≥ 50%;
   • QTcF interval on electrocardiogram < 450 ms (males) or < 470 ms (females).

7. Subjects of reproductive potential (including male subjects) must agree to avoid pregnancy and use effective contraceptive measures with their partners during the study period and for 6 months after the last dose. A negative serum pregnancy test must be confirmed between screening and prior to the first dose.

Exclusion Criteria:

1. Any active autoimmune disease, or a history of autoimmune disease requiring systemic steroid therapy, with a daily prednisone dose > 10 mg or equivalent corticosteroid within 2 weeks prior to study treatment.
2. Uncontrolled seizures, hypertension, or psychiatric disorder at screening.
3. Severe infection occurring within 4 weeks prior to the first dose, including but not limited to complicated infection requiring hospitalization, sepsis, or severe pneumonia; active infection requiring systemic anti-infective therapy within 2 weeks prior to the first dose, except for antiviral therapy for hepatitis B or hepatitis C.
4. Third-space effusion that cannot be effectively controlled by drainage or other measures.
5. Participation in another clinical trial of an investigational drug within 4 weeks prior to enrollment.
6. Receipt of any anti-tumor therapy including chemotherapy, targeted therapy, biologic therapy, immunotherapy, radical radiotherapy, or major surgery within 2 weeks prior to enrollment or within 3 half-lives (whichever is shorter).
7. Any other active malignancy within 5 years prior to enrollment. Subjects with other malignancies cured by local therapy (e.g., basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix) are excepted.
8. Patients with hyperthyroidism are excluded. Subjects with hypothyroidism on a stable dose of thyroid hormone replacement therapy with stable thyroid function (TSH ≤ 10 μIU/mL and no clinical manifestations of hypothyroidism) may be enrolled.
9. Failure to recover from all adverse events due to prior therapy to Grade ≤ 1 (per CTCAE v5.0) or to baseline levels, except for toxicities deemed by the investigator to pose no safety risk (such as alopecia, Grade 2 peripheral neuropathy, hypothyroidism stabilized with hormone replacement therapy, etc.).
10. Any active cardiac disease within 6 months prior to the first dose, including New York Heart Association (NYHA) Class II-IV cardiac dysfunction, congestive heart failure, myocardial infarction, unstable angina, and/or stroke or other cardiovascular or cerebrovascular events of Grade 3 or higher, or left ventricular ejection fraction (LVEF) < 50%.
11. HIV infection, active HBV infection (HBV DNA above the upper limit of normal), or active HCV infection (HCV RNA above the upper limit of normal).
12. Any other serious systemic disease or any other condition that, in the opinion of the investigator, would render the subject ineligible for participation in this clinical study.