A Single-Arm,Multicenter Phase, Phase II Clinical Trial of Adebrelimab Combined With Trametinib in the Treatment of Refractory Recurrent Langerhans Cell Histiocytosis in Children and Adolescents

1. LCH diagnostic criteria: lesion biopsy pathology for LCH, immunohistochemical CD1a and/or CD207 (Langerin) positive [refer to the Chinese Children's Histiocytic Group (CCHG) CCHG-LCH-2019 research protocol];
2. Cases must meet one of the following criteria for refractory or relapsed LCH:

1) Refractory LCH: SS-LCH patients have responded to at least first-line therapy and have not met improvement criteria with second-line treatments based on klatropine or clofarabine; or MS-LCH patients do not achieve improvement after one course of first-line treatment; 2) Recurrent LCH: After complete response in SS-LCH or MS-LCH patients, new lesions reappear or the original lesion enlarges again.

3. Age 1-18 years; 4. All patients must sign informed consent forms. 5. ECOG PS score: 0-1; (Or according to the Karnofsky/Lansky Performance State Scale, performance score >=50%) 6. Expected survival time≥ 6 months; 7. Essential organ functions are basically normal:

1. Good cardiac function: echocardiography shows cardiac ejection fraction ≥50%, ECG shows no obvious abnormalities;
2. Good renal function: serum creatinine ≤2.0×ULN;
3. Good liver function: ALT and AST ≤ 5.0×ULN; Total bilirubin ≤ 2.5× ULN (Gilbert syndrome requires total bilirubin ≤ 3.0× ULN); For patients with liver disease caused by histiocytosis: abnormal levels of bilirubin, aspartate aminotransferase, alanine aminotransferase, and albumin may be observed.
4. Good bone marrow proliferation: absolute neutrophil count (ANC) ≥1.0×109/L, hemoglobin ≥80 g/L (may receive red blood cell transfusion), platelet count ≥ 75×109/L (transfusion-independent, defined as no platelet transfusion within 7 days prior to enrollment).
5. Blood oxygen saturation >91% when not receiving oxygen;

Exclusion Criteria:

1. Those who have used similar anti-PD-1 or anti-PD-L1 monoclonal antibodies or related pathway targeted drugs;
2. Participating in other clinical investigators simultaneously;
3. Previous treatment toxicity has not recovered and remains above grade 1 (CTCAE V5.0 criteria) (excluding alopecia and neurotoxicity);
4. Those allergic to the active ingredients and excipients of the investigational drugs trimetinib and/or adezbelizumab;
5. History of autoimmune diseases, including but not limited to systemic lupus erythematosus, psoriasis, rheumatoid arthritis, inflammatory bowel disease, Hashimoto's thyroiditis, etc.;
6. Individuals with a past or current active tuberculosis infection;
7. Active infections requiring systemic treatment;
8. Complicated by serious diseases, including but not limited to: uncontrolled diabetes, active peptic ulcers, etc.;
9. Positive antibodies against HIV, TP, HCV, HBV Ag, and HBV DNA copy count above the upper limit of normal detection units;
10. Thyroid dysfunction (FT3, FT4, T3, T4);
11. Administering live or attenuated vaccines within 4 weeks before dosing, during treatment, or within 5 months after the last dose;
12. Candidates deemed unsuitable for the trial due to other reasons determined by the investigator;
13. Those who, due to personal reasons, are unable to follow the established plan during treatment;