To Evaluate the Efficacy, Safety, and PK Characteristics of FCN-159 in Pediatric Patients With Refractory/Recurrent LCH

Inclusion Criteria:

1. Age 2-16 (inclusive)

2. Patients with histologically confirmed Langerhans cell histiocytosis (LCH) diagnosedby the central laboratory.

3. If sufficient tumor tissue samples and peripheral blood samples are available,central laboratory biomarker testing is required as follows: including but notlimited to ERBB3, BRAF, ARAF, HRAS, KRAS, NRAS, MEK (MAP2K1 and MAP2K2), and otherMEK upstream genes.If inability to get tissue, the gene testing results from a locallaboratory also can be accepted.

4. Patients who have received at least prior first-line systemic treatment, defined astreatment including vinblastine (VBL) and glucocorticoids for at least 2 weeks. VBLcan 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 liverimpairment (liver enzyme elevation ≥ 5 × upper limit of normal (ULN) and bilirubinelevation ≥ 1.5 × ULN), severe neurotoxicity related to vinca alkaloids,chemotherapy-related intracranial hypertension, or grade 4 bone marrow depressionwith severe infection (sepsis, severe pneumonia, etc.) after chemotherapy.

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

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

7. Initial response of the disease to first or second-line systemic treatment isNAD or AD-better or AD-stable, followed by disease reactivation aftermaintenance therapy for more than 3 months. Second-line treatment includescytarabine and/or cladribine.

8. Persistent mutated gene positive in plasma free DNA testing during priortreatment (confirmed by 2 consecutive tests) or retest positive after treatmentdiscontinuation;

9. Lack of regression in the affected central nervous system (including thepituitary gland) after treatment;

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

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

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

13. Expected survival at least ≥ 3 months;

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

15. Patients or their legal guardians must be able to understand and willingly sign awritten informed consent form.

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

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

18. 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, bloodproducts, or granulocyte colony-stimulating factors. Patients with hematocytopeniabelow these thresholds due to the underlying disease may be considered for inclusionbased on the investigator's comprehensive judgment.

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

20. Coagulation: International normalized ratio (INR) and activated partialthromboplastin time (APTT) ≤ 1.5 ULN.

Exclusion Criteria:

1. Patients who have received any of the following prior treatments:

2. Chemotherapy, targeted therapy, immunotherapy, biologic therapy, or herbalanti-tumor therapy for LCH within 4 weeks or < 5 half-lives (whichever isshorter)before the start of the study drug .

3. Strong CYP3A4, CYP2C8, and CYP2C9 inhibitors or inducers within 14 days beforethe start of the study drug, except for topical skin application.

4. Gowth factors that promote platelet or white blood cell count or functionwithin 7 days before the start of the study drug.

5. Radiotherapy or major surgical treatment (including craniotomy, thoracotomy,laparotomy, open bone or joint surgery, etc.) within 4 weeks before the startof the study drug.

6. Participated in other interventional clinical trials within 4 weeks before thestart of the study drug.

7. MEK 1/2 inhibitors (those who have received this treatment for a short periodof ≤ 2 weeks may be included).

8. Anticoagulants within 7 days before the start of the study drug for patientswith brain tumors (intracranial masses).

9. Prednisone treatment < 0.5mg/kg/day (or equivalent dose of othercorticosteroids) is allowed within one month before enrollment, but must bediscontinued 14 days before the start of the study drug. Patients with brainlesions receiving corticosteroid therapy for brain edema must maintain a stabledose for 14 days before enrollment. Hormone replacement therapy is allowed forpatients with hypopituitarism due to primary disease involvement of thepituitary.

10. Patients with a history of other malignant tumors or concurrent other malignanttumors (excluding cured non-melanoma skin basal cell carcinoma, ductal carcinoma insitu of the breast, or cervical carcinoma in situ).

11. Uncontrolled hypertension (with medication treatment): Blood pressure (BP) greaterthan or equal to the 95th percentile for age, height, and sex, as described inAppendix 6.

12. Patients with dysphagia, active gastrointestinal disease, malabsorption syndrome, orother conditions that may affect the absorption of the study drug.

13. Prior or current history of retinal vein obstruction (RVO), retinal pigmentepithelial detachment (RPED), glaucoma, and other clinically significant abnormalophthalmologic examination results.

14. Interstitial pneumonia, including clinically significant radiation pneumonitis.Except for interstitial pneumonia caused by pulmonary involvement of the primarydisease.

15. Patients will be excluded if their cardiac function or comorbidities meet any of thefollowing criteria:

16. During the screening period, 12-lead electrocardiogram (ECG) measurements willbe taken three times at the study center with a mean value calculated using theQTcF formula provided by the instrument; patients with a mean value of QTcF > 470 milliseconds or with risk factors for QTcF prolongation, such asuncorrected hypokalemia, congenital long QT syndrome, or receiving drugs knownto prolong QTcF interval (mainly class Ia, Ic, and III antiarrhythmic drugs)will be excluded from the study. Drugs with the potential to prolong the QTcFinterval are listed in Appendix 7.

17. New York Heart Association (NYHA) Class 2 and above congestive heart failure asshown in Appendix 5.

18. Clinically significant arrhythmias, including but not limited to complete leftbundle branch block, and second-degree atrioventricular block.

19. Known presence of clinically significant coronary heart disease,cardiomyopathy, or severe valvular disease.

20. Echocardiography examination indicating left ventricular ejection fraction (LVEF) < 50%.

21. Patients with active bacterial, fungal, or viral infections, including activehepatitis B (defined as positive hepatitis B surface antigen and hepatitis B virusDNA > 1000IU/ml or meeting the diagnostic criteria for active hepatitis B infectionat the study center) or hepatitis C (positive hepatitis C virus RNA), or humanimmunodeficiency virus (HIV positive) infection.

22. Patients with known allergies to the study drug, other MEK1/2 inhibitors, or theirexcipients.

23. Patients with known tumor tissue genetic testing that indicates the presence ofMAP2K1 exon 3 deletions (del) or deletion-insertion type (delins/indels) mutations.

24. The investigator considers clinically significant cases that will impedeparticipation in the study or prevent compliance with safety requirements.