Phase II Exploratory Study of Sequential Triple Therapy (Temozolomide/Anlotinib/Bemarituzumab) in Combination With Concurrent Radiotherapy With Temozolomide and Anlotinib for the Maintenance Treatment of Diffuse Midline Gliomas in Children

inclusion criteria 1.Age 3-18 years old, gender not limited； 2. Pathological diagnosis of diffuse midline gliomas in children;； 3. Not achieving complete surgical resection； 4. According to the 2021 WHO Classification of Central Nervous System Tumors (Fifth Edition) ； 5. Have not received specialized treatment for diffuse midline gliomas in children in the past;； 6. According to RECIST version 1.1 standard, at least one assessable target lesion is required; 7. ECOG physical fitness status is 0-4 points; 8. The main organ function is normal, which meets the following criteria:

1. The standard for blood routine examination must meet the following criteria: (no blood transfusion within 14 days)

   1. Hb≥90g/L:
   2. ANC≥1.5\*10\^9/L;
   3. PLT≥80\*10\^9／L；
2. Biochemical tests must meet the following standards

   1. BIL\<1.25 times the upper limit of normal (ULN);
   2. ALT and AST\<2.5\*ULN;
   3. Serum Cr ≤ ULN, endogenous creatinine clearance rate\>50ml/min (Cockcroft Gaut formula); 9. Sign a written informed consent form before conducting any experimental activities; 10. Researchers determine that they are able to comply with the research protocol; 11. Negative pregnancy test (for female patients with fertility) during screening; 12. Male patients with fertility and female patients with fertility and pregnancy risk must agree to use two contraceptive methods throughout the study period (at least one of which is considered an effective contraceptive method).

      Female patients who do not have fertility (i.e. meet at least one of the following criteria):
      * Have undergone hysterectomy and/or bilateral oophorectomy with documented records;
      * medically confirmed ovarian dysfunction;
      * Postmenopausal status, defined as a state of continuous cessation of menstruation for at least 12 months without other pathological or physiological reasons, and confirmed by serum follicle stimulating hormone (FSH) levels consistent with postmenopausal status.

      A signed and dated informed consent form indicating that the patient (or legal representative, if permitted by local guidelines/practices) has been informed of all relevant aspects of the study.

      13\. Patients who are willing and able to comply with visit arrangements, treatment plans, laboratory tests, and other research procedures.

      exclusion criteria
      1. Previously received anti-tumor treatment for diffuse midline glioma;
      2. Previous or concurrent malignant tumors (excluding malignant tumors that have been cured and have a cancer free survival of more than 5 years, such as basal cell carcinoma of the skin, cervical carcinoma in situ, and papillary thyroid carcinoma);
      3. Uncontrolled clinical symptoms or diseases of the heart, such as: (1) NYHA grade II or above heart failure (2) unstable angina pectoris (3) myocardial infarction within 1 year (4) clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention in patients;
      4. Active infections that require treatment;
      5. People with congenital or acquired immune deficiency (such as HIV infected people), active hepatitis B (HBV-DNA ≥ 104 copies/ml or 2000IU/ml) or hepatitis C (hepatitis C antibody is positive, and HCV-RNA is higher than the detection limit of the analytical method);
      6. Known history of substance abuse, alcoholism, or drug use;
      7. According to the researcher's judgment, there may be other factors that could force the subject to terminate the study midway, such as suffering from other serious illnesses (including mental illnesses) that require concurrent treatment, severe abnormal laboratory test values, family or social factors that may affect the subject's safety or the collection of trial data;
      8. Patients who the surgeon believes can undergo curative resection;
      9. Active pulmonary tuberculosis;
      10. Serious infections (including but not limited to hospitalization due to infection, bacteremia, or complications of severe pneumonia) that occurred within 4 weeks prior to the start of the study treatment.