Clinical trial NCT07004075: FCN-159 Monotherapy Versus Chemotherapy by Investigator's Choice in Pediatric Low-grade Glioma Patients With BRAF Alteration
Official title: An Open-label, Randomized, Multi-center Phase III Clinical Study: Aim to Evaluate the Efficacy and Safety of FCN-159 Monotherapy Versus the Treatment by Investigator's Choice in Patients With Pediatric Low-grade Glioma Harboring KIAA1549-BRAF Fusion or BRAF V600E Mutation
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Low-grade Glioma
Pediatric Low-grade Gliomas
pLGG With BRAF Alteration
Lead sponsor: Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.
Sponsor class: INDUSTRY
First posted: 2025-06-04
Enrollment: 102
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: An open-label, randomized, multi-center phase III clinical study: Aim to evaluate the efficacy and safety of FCN-159 monotherapy versus the treatment by investigator's choice in patients with pediatric low-grade glioma harboring KIAA1549-BRAF fusion or BRAF V600E mutation


Eligibility criteria: Inclusion Criteria:

1. Pediatric patients aged between ≥ 2 years and \< 18 years; regardless of male or female.
2. Histologically and/or cytologically confirmed diagnosis of low-grade glioma (pLGG diagnosis 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, including patients 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 two dimensions 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 organ function within 14 days before enrollment.

Exclusion Criteria:

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

   1. Patients who have received chemotherapy drugs or traditional Chinese medicines or herbals with definitive anti-tumor treatment within 4 weeks preceding the first dose of investigational drug;
   2. Patients who have received growth factors that promote platelet or leukocyte count or function within 14 days preceding the first dose of investigational drug;
   3. Patients who received radiotherapy, surgery or immunotherapy within 4 weeks preceding the first dose of investigational drug;
   4. Patients who have participated in other interventional clinical trials within 4 weeks before receiving the first dose of investigational drug;
   5. Patients who have received live vaccines within 4 weeks preceding the first dose of investigational drug, or patients who have received inactivated vaccines and mRNA vaccines within 14 days preceding the study treatment;
   6. Patients who have previously received any other MEK 1/2 inhibitors such as Selumetinib or BRAF inhibitors such as Dabrafenib.
2. Patients with high-grade gliomas, as well as schwannoma, subependymal giant cell astrocytoma (tuberous sclerosis), and diffuse intrinsic pontine gliomas (even if the histological diagnosis is WHO Grade 1 or 2).
3. Patients who require endotracheal intubation for assisted ventilation or tracheotomy should be excluded.
4. Patients who have uncontrollable epilepsy as assessed by the investigator.
5. Patients with dysphagia, active GI diseases, malabsorption syndrome, or other conditions that will interfere with the absorption of the investigational drug.
6. Patients with clinically significant active bacterial, fungal or viral infections, including hepatitis B virus surface antigen positive and hepatitis B virus DNA exceeding 1000 IU/ml. Hepatitis B carriers are allowed to be enrolled. Patients with positive hepatitis C virus (HCV) antibody test; those who have confirmed human immunodeficiency virus (HIV) infection, and are unwilling to undergo HIV testing.
7. Patients with history or current evidence of retinal vein obstruction (RVO), retinal pigment epithelial detachment (RPED), central retinal vein occlusion, glaucoma, and other significant abnormalities in ophthalmological examinations.
8. Interstitial pneumonia, including clinically significant radiation pneumonitis.
9. Grade 3 creatine phosphokinase increased (\>5 × ULN - 10 × ULN).

Primary outcomes:
measure: Compare the progression free survival (PFS) of FCN-159 versus chemotherapy by IRC
timeFrame: up to 48 months
Secondary outcomes:
measure: PFS of FCN-159 versus chemotherapy by INV
timeFrame: up to 48 months
measure: Objective response rate (ORR) of FCN-159 versus chemotherapy
timeFrame: up to 48 months
measure: Clinical benefit rate (CBR) of FCN-159 versus chemotherapy
timeFrame: up to 48 months
measure: Duration of overall response (DOR) of FCN-159 versus chemotherapy
timeFrame: up to 48 months
measure: Time to response (TTR) of FCN-159 versus chemotherapy
timeFrame: up to 48 months
measure: Overall survival (OS) of FCN-159 vesus chemotherapy
timeFrame: up to 48 months
measure: Safety of FCN-159 versus chemotherapy
timeFrame: up to 48 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital, Capital Medical University
state: Beijing
Study officials:
References: