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

NCT07004075 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: FCN-159-010
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

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

Conditions

Low-grade Glioma; Pediatric Low-grade Gliomas; pLGG With BRAF Alteration

Outcome Measures

Primary Outcomes (1)

• Compare the progression free survival (PFS) of FCN-159 versus chemotherapy by IRC

  PFS assessed per RANO-LGG criteria by IRC, and defined as the time from randomization to the first recorded progressive disease or death from any cause, whichever is first

  up to 48 months

Secondary Outcomes (7)

• PFS of FCN-159 versus chemotherapy by INV

  up to 48 months

• Objective response rate (ORR) of FCN-159 versus chemotherapy

  up to 48 months

• Clinical benefit rate (CBR) of FCN-159 versus chemotherapy

  up to 48 months

• Duration of overall response (DOR) of FCN-159 versus chemotherapy

  up to 48 months

• Time to response (TTR) of FCN-159 versus chemotherapy

  up to 48 months

Study Arms (2)

Experimental arm: Luvometinib

EXPERIMENTAL

FCN-159, 5 mg/m\^2, once daily, continuous oral administration

Drug: Luvometinib

Comparator: investigator's choice of chemotherapy

ACTIVE COMPARATOR

Chemotherapeutic Agent COG-V/C, intravenous solution for injection Carboplatin + Vindesine, intravenous solution for injection Carboplatin, intravenous solution for injection Temozolomide, orally Day 1 to Day 5 of each 28 days as a cycle

Biological: Chemotherapeutic Agent COG-V/C Carboplatin + Vindesine, Carboplatin, Temozolomide

Interventions

Luvometinib DRUG

Luvometinib oral tablet

Experimental arm: Luvometinib

Chemotherapeutic Agent COG-V/C Carboplatin + Vindesine, Carboplatin, Temozolomide BIOLOGICAL

Investigator's choice of chemotherapy administered IV or orally

Comparator: investigator's choice of chemotherapy

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Pediatric patients aged between ≥ 2 years and \< 18 years; regardless of male or female.
• 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).
• KIAA1549-BRAF fusion or BRAF V600E mutation-positive.
• Patients requiring systemic therapy as determined by the investigator, including patients having disease recurrence or progression, or residual disease of surgery, or unresectable.
• 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.
• \. Karnofsky performance score or Lansky performance score ≥ 70. 7．Adequate organ function within 14 days before enrollment.

You may not qualify if:

• Patients who have previously received any of the following treatments:
• 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;
• Patients who have received growth factors that promote platelet or leukocyte count or function within 14 days preceding the first dose of investigational drug;
• Patients who received radiotherapy, surgery or immunotherapy within 4 weeks preceding the first dose of investigational drug;
• Patients who have participated in other interventional clinical trials within 4 weeks before receiving the first dose of investigational drug;
• 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;
• Patients who have previously received any other MEK 1/2 inhibitors such as Selumetinib or BRAF inhibitors such as Dabrafenib.
• 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).
• Patients who require endotracheal intubation for assisted ventilation or tracheotomy should be excluded.
• Patients who have uncontrollable epilepsy as assessed by the investigator.
• Patients with dysphagia, active GI diseases, malabsorption syndrome, or other conditions that will interfere with the absorption of the investigational drug.
• 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.
• 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.
• Interstitial pneumonia, including clinically significant radiation pneumonitis.
• Grade 3 creatine phosphokinase increased (\>5 × ULN - 10 × ULN).

Sponsors & Collaborators

• Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.: lead

Study Sites (1)

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100070, China

Location

MeSH Terms

Interventions

Vindesine; Carboplatin; Temozolomide

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Coordination Complexes; Organic Chemicals; Dacarbazine; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Central Study Contacts

Wenbin Li

CONTACT

+86 1530137799; neure55@126.com

Zhuang Kang

CONTACT

+86 15011281069; kzhaoren1984@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2025
• First Posted: June 4, 2025
• Study Start: June 30, 2025
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2029
• Last Updated: June 4, 2025

Record last verified: 2025-05

Locations

CN (1)