Reference Detail

Ref Type

Abstract

PMID

Authors

W. Li Y. Mao Z. Kang W. Hua S. Li Z. Wu H. Liu J. Hu J. Guo W. Zhong X. Wang

Title

499O A phase II study to explore the efficacy and safety of FCN-159 in recurrent or progressive pediatric low-grade glioma (pLGG) with MAPK pathway-activated

Journal	Vol	Issue	Date	Pages	Journal Short Title
Annals of Oncology	34	Supplement 2	Oct 2023

URL

https://www.annalsofoncology.org/article/S0923-7534(23)02530-9/fulltext

Abstract Text

The MAPK pathway over-activation is the primary driver in most of pLGG, mainly including BRAFV600E, KIAA1549-BRAF fusion and NF1mut with limited therapeutic options available. FCN-159 is an oral inhibitor of MEK1/2 with highly potent selectivity, and is expected to be an efficacious targeted therapy of pLGG. A multi-center, single-arm phase II study was designed to evaluate safety and efficacy of FCN-159 in pediatric patients (pts) with recurrent or progressive LGG. Methods Pediatric pts with recurrent or progressive LGG were enrolled and received FCN-159 monotherapy continuously 5mg/m2 once daily based on body surface area (BSA). The primary endpoint was to assess preliminary efficacy of FCN-159 by RANO criteria. Results As the cut-off date of July 31th, 2023, 23 subjects have been enrolled. Median age is 8 years (range: 3-17) at study entry, 56.5% were female. All pts were identified as BRAF or NF1 alterations (BRAFV600E 12/23, 52.2%, KIAA1549-BRAF fusion 8/23, 34.8% and NF1mut 3/23, 13.0%). At a median follow-up of 7.79 months, 22 pts were evaluated for efficacy: 6 partial response (PR, 27.3%, unconfirmed PR 3), 9 minor response (MR, 40.9%, unconfirmed MR 2), and 7 stable disease (SD, 31.8%). Among 23 pts, 22 pts (95.7%) experienced treatment-emergent adverse events (TEAEs), which were reported to be drug-related. Most common TEAEs (incidence ≥ 20%) included blood lactate dehydrogenase increased, α-hydroxybutyrate dehydrogenase increased, blood creatine phosphokinase increased, upper respiratory tract infection, paronychia and rash. Majority were grade 1 or 2, and 2 pts reported grade 3, no grade 4 or above reported. One pt experienced serious adverse event as liver function test abnormal. TEAEs leading to drug interruption were reported in 16 pts, and 10 pts were related to study drug. No TEAEs leading to drug dose reduction, discontinuation or death were reported. Conclusions The preliminary study results showed that treatment of FCN-159 was remarkably efficacious for pLGG pts. FCN-159 is well tolerated and easily manageable, without new safety signal observed. Long-term efficacy and safety follow-up are ongoing.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
BRAF V600E	low grade glioma	predicted - sensitive	FCN-159	Phase II	Actionable	In a Phase II trial, FCN-159 treatment was well tolerated and resulted in 6 partial responses, 9 minor responses, and 7 with stable disease in 22 pediatric patients with low-grade glioma harboring BRAF V600E (12/23), KIAA1549-BRAF (8/23), or NF1 mutations (3/23) (Ann Oncol (2023) 34 (suppl_2): S391-S392).	detail...