• Age 2-16 (inclusive)

• Patients with histologically confirmed Langerhans cell histiocytosis (LCH) diagnosed by the central laboratory.

• If sufficient tumor tissue samples and peripheral blood samples are available, central laboratory biomarker testing is required as follows: including but not limited to ERBB3, BRAF, ARAF, HRAS, KRAS, NRAS, MEK (MAP2K1 and MAP2K2), and other MEK upstream genes.If inability to get tissue, the gene testing results from a local laboratory also can be accepted.

• Patients who have received at least prior first-line systemic treatment, defined as treatment including vinblastine (VBL) and glucocorticoids for at least 2 weeks. VBL can be substituted with vincristine (VCR) or vindesine (VDS). Alternatively, patients may be unable to tolerate chemotherapy due to severe chemotherapy toxicity. Inability to tolerate chemotherapy is defined as one of the following: Severe liver impairment (liver enzyme elevation ≥ 5 × upper limit of normal (ULN) and bilirubin elevation ≥ 1.5 × ULN), severe neurotoxicity related to vinca alkaloids, chemotherapy-related intracranial hypertension, or grade 4 bone marrow depression with severe infection (sepsis, severe pneumonia, etc.) after chemotherapy.

• Refractory/relapsed LCH is defined as the presence of one of the following:

∙ Failure of prior treatment, i.e., no regression in risk organs after at least 2 weeks of systemic treatment, or overall evaluation of AD-progression or AD-mix;

‣ Initial response of the disease to first or second-line systemic treatment is NAD or AD-better or AD-stable, followed by disease reactivation after maintenance therapy for more than 3 months. Second-line treatment includes cytarabine and/or cladribine.

‣ Persistent mutated gene positive in plasma free DNA testing during prior treatment (confirmed by 2 consecutive tests) or retest positive after treatment discontinuation;

‣ Lack of regression in the affected central nervous system (including the pituitary gland) after treatment;

‣ Presence of bone marrow involvement and/or hemophagocytic lymphohistiocytosis (HLH);

• Presence of evaluable lesions based on PET response criteria (PRC).

• Patients who have to have recovered from all acute toxic effects of prior anti-tumor therapy, and all relevant toxicities must be ≤ grade 1 (except for alopecia and ototoxicity).

• Expected survival at least ≥ 3 months;

• Lansky (≤ 15 years old) and Karnofsky (≥ 16 years old) performance status scores should be ≥ 50%, as shown in Appendix 4.

⁃ Patients or their legal guardians must be able to understand and willingly sign a written informed consent form.

⁃ For women of childbearing potential, a serum human chorionic gonadotropin (HCG) pregnancy test must be negative within 7 days before starting treatment.

⁃ For female patients of childbearing potential: Patients should agree to use effective contraception methods during the treatment period and for at least 90 days after the last dose of study treatment, using dual barrier contraception methods such as condoms, oral or injectable contraceptives, intra-uterine contraceptive devices, etc. Male patients should agree to refrain from donating sperm for at least 90 days after the last dose of study treatment.

⁃ Adequate bone marrow function: Absolute neutrophil count ≥ 1.0×10\^9/L, hemoglobin ≥ 90g/L, and platelets ≥ 75×10\^9/L without the use of blood transfusions, blood products, or granulocyte colony-stimulating factors. Patients with hematocytopenia below these thresholds due to the underlying disease may be considered for inclusion based on the investigator's comprehensive judgment.

⁃ Adequate hepatic and renal function: Serum total bilirubin ≤ 1.5 × the upper limit of normal (ULN), or ≤ 5× ULN for patients with Gilbert's syndrome or liver involvement; aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (AKP) ≤ 2.5 × ULN, or ≤ 10 × ULN for patients with liver involvement; albumin ≥ 3g/dL; and creatinine clearance or isotopic glomerular filtration rate (GFR) ≥ 50ml/min/1.73㎡or serum creatinine based on age; hepatic and renal impairment caused by the primary disease may be considered for inclusion based on the investigator's comprehensive judgment.

⁃ Coagulation: International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 ULN.