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

Background

The MAPK pathway over-activation is the primary driver in most of pLGG, mainly including BRAF^V600E, KIAA1549-BRAF fusion and NF1^mut 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 31^th, 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 (BRAF ^V600E 12/23, 52.2%, KIAA1549-BRAF fusion 8/23, 34.8% and NF1 ^mut 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.

Clinical trial identification

ChiCTR2300069156.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Shanghai Fosun Pharmaceutical Development Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.