Discussion
cancers, tumor, fatigue, NF1-related, NF1
MALIGNANCIES, TUMOR, CANCERS
This phase I trial demonstrated that FCN-159 had low rates of DLT in adults with inoperable NF1-related PN and was associated with sustained reduction in PN tumor volumes. The MTD and RP2D were determined to be 8 mg daily with good tolerability and sustainable antitumor activity.In the phase 1a study of FCN-159 in patients with advanced On the basis of this phase I trial, FCN-159 appears to have a favorable safety profile among similar drugs in its class. The first-in-human study of selumetinib had up to 71.4% of patients reporting AEs of CTCAE grade 3 or above, of which fatigue was the most common [Of the 16 patients whose tumor responses were evaluable, 37.5% had PRs. A previous study of mirdametinib showed a response rate of 42% in adults with NF1-related PN [The RP2D of FCN-159 was determined as 8 mg daily, while it was 25 mg/mThis study is limited by its small study size and the narrow ethnic backgrounds of the trial patients. Although an NF1 mutation test was not mandatory according to the protocol, all patients underwent one genetic test after enrollment; these results are presented in Table This study has taken a robust 3 + 3 approach to determining the RP2D for FCN-159. It included a cohort of adults with PN for whom there are currently no treatment options, suggesting that FCN-159 will be of great benefit for adults with NF-1-related PN, for whom there is currently no approved drug. As FCN-159 is a MEK inhibitor, it is hoped that these results may contribute to the understanding of treatment to numerous cancers, not only NF-1-related malignancies. The RP2D is being taken forward to an ongoing trial, and additionally, these data are being used to inform a phase I pediatric study.