FCN-159 Monotherapy Versus Chemotherapy by Investigator's Choice in Pediatric Low-grade Glioma Patients With BRAF Alteration

Inclusion Criteria:

1. Pediatric patients aged between ≥ 2 years and < 18 years; regardless of male orfemale.

2. Histologically and/or cytologically confirmed diagnosis of low-grade glioma (pLGGdiagnosis as Grade 1 or 2 according to the 2021 WHO classification of CNS).

3. KIAA1549-BRAF fusion or BRAF V600E mutation-positive.

4. Patients requiring systemic therapy as determined by the investigator, includingpatients having disease recurrence or progression, or residual disease of surgery,or unresectable.

5. At least one intracranial measurable lesion that can be reproducibly measured in twodimensions on T2-FLAIR, with the minimum size of the bi-perpendicular diameter of ≥ 10 mm, and can be visible on two or more imaging slice.

6. Karnofsky performance score or Lansky performance score ≥ 70. 7．Adequate organfunction within 14 days before enrollment.

Exclusion Criteria:

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

2. Patients who have received chemotherapy drugs or traditional Chinese medicinesor herbals with definitive anti-tumor treatment within 4 weeks preceding thefirst dose of investigational drug;

3. Patients who have received growth factors that promote platelet or leukocytecount or function within 14 days preceding the first dose of investigationaldrug;

4. Patients who received radiotherapy, surgery or immunotherapy within 4 weekspreceding the first dose of investigational drug;

5. Patients who have participated in other interventional clinical trials within 4weeks before receiving the first dose of investigational drug;

6. Patients who have received live vaccines within 4 weeks preceding the firstdose of investigational drug, or patients who have received inactivatedvaccines and mRNA vaccines within 14 days preceding the study treatment;

7. Patients who have previously received any other MEK 1/2 inhibitors such asSelumetinib or BRAF inhibitors such as Dabrafenib.

8. Patients with high-grade gliomas, as well as schwannoma, subependymal giant cellastrocytoma (tuberous sclerosis), and diffuse intrinsic pontine gliomas (even if thehistological diagnosis is WHO Grade 1 or 2).

9. Patients who require endotracheal intubation for assisted ventilation or tracheotomyshould be excluded.

10. Patients who have uncontrollable epilepsy as assessed by the investigator.

11. Patients with dysphagia, active GI diseases, malabsorption syndrome, or otherconditions that will interfere with the absorption of the investigational drug.

12. Patients with clinically significant active bacterial, fungal or viral infections,including hepatitis B virus surface antigen positive and hepatitis B virus DNAexceeding 1000 IU/ml. Hepatitis B carriers are allowed to be enrolled. Patients withpositive hepatitis C virus (HCV) antibody test; those who have confirmed humanimmunodeficiency virus (HIV) infection, and are unwilling to undergo HIV testing.

13. Patients with history or current evidence of retinal vein obstruction (RVO), retinalpigment epithelial detachment (RPED), central retinal vein occlusion, glaucoma, andother significant abnormalities in ophthalmological examinations.

14. Interstitial pneumonia, including clinically significant radiation pneumonitis.

15. Grade 3 creatine phosphokinase increased (>5 × ULN - 10 × ULN).