FCN-159, a MEK1/2 inhibitor, in patients with advanced melanoma harboring NRAS or NF1mutations: A phase 1B dose-expansion study.

• DOI: 10.1200/jco.2024.42.16_suppl.3095
• Publication Date: 2024-06-17T14:03:51Z
• Authors: Junjie Gu; Lili Mao; Jun Guo; Yu Jiang; Lingjun Zhu; Xiaoshi Zhang; Wangjun Yan; Yu Chen; Chang Tan; Weiyou Zhu; Jian Zhang; Jie Liu; Jing Lin; Zhuli Wu; Xingli Wang; Yuchen Yang; Ben Li; Lu Si
• Keywords: 03 medical and health sciences; 0302 clinical medicine

3095 Background: In phase 1A dose-escalation study, preliminary anti-tumor activity of FCN-159 was observed in advanced melanoma patients harboring NRAS mutations (ORR: 19.0%, mPFS: 3.8 months) with tolerable safety profile, which posted during AACR 2022 (No.: 22-LB-7398-AACR). Here, we report the results from 1B dose-expansion study NRAS- or NF1-mutant at RP2D predetermined 12 mg. Methods: This open-label, dose-expansion, (NCT03932253) consists two cohorts, enrolled unresectable stage III/IV NF1 mutations, respectively. Patients received orally mg once daily (QD) continuously 28-day cycles. The primary endpoint activity. Results: As July 17, 2023, 46 (32 NRASmutations Cohort 1 and 14 NF1mutations 2) were QD. median follow-up time 8.6 months. Among 25 who failed previous anti-PD-1 therapy 1, 6 had confirmed partial responses (ORR, 24.0%; 95% confidence interval [CI], 9.4–45.1). Median DOR 6.5 months (95% CI, 2.7–NE). progression-free survival (mPFS) 3.6 1.8–5.5). 2, PR 7.1%; 0.2-33.9) mPFS 2.8 1.8-5.5) (Table). Grade≥3 FCN-159-related treatment-emergent adverse events (TEAEs) reported 10 (21.7%) both cohorts; most common blood creatine phosphokinase increased (13.0%). FCN-159–related serious AEs (SAEs) 3 (6.5%) patients, edema lower limb, cellulitis pneumonia. Two (4.3%) discontinued treatment due to related TEAEs, including serous retinal detachment herpes zoster. No TEAEs led death. Conclusions: showed encouraging efficacy data well tolerated profile NRAS-mutant melanoma, especially those therapy. Clinical trial information: NCT03932253 . [Table: see text]