Meeting
2024 ASCO Annual Meeting
FCN-159, a MEK1/2 inhibitor, in patients with advanced melanoma harboring NRAS or NF1mutations: A phase 1B dose-expansion study.
Authors
Junjie Gu
Department of Melanoma and Sarcoma, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China
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
Organizations
Department of Melanoma and Sarcoma, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China, Beijing Cancer Hospital, Beijing, China, West China Hospital, Sichuan University, Chengdu, China, Jiangsu Province Hospital, Nanjing, Jiangsu, China, Sun Yat-Sen University Cancer Center, Guangzhou, China, Fudan University Shanghai Cancer Center; Shanghai Medical College, Fudan University, Shanghai, China, Fujian Cancer Hospital, Fuzhou, China, Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China, Fudan University Shanghai Cancer Center, Shanghai, China, West China Hospital of Sichuan University, Chengdu, China, Shanghai Fosun Pharmaceutical Industrial Development CO., Ltd., Shanghai, China
Research Funding
No funding sources reported
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 was posted during AACR 2022 (No.: 22-LB-7398-AACR). Here, we report the results from phase 1B dose-expansion study in advanced NRAS- or NF1-mutant melanoma patients at RP2D predetermined at 12 mg. Methods: This open-label, dose-expansion, phase 1B study (NCT03932253) consists of two cohorts, which enrolled patients with unresectable stage III/IV melanoma harboring NRAS or NF1 mutations, respectively. Patients received FCN-159 orally at 12 mg once daily (QD) continuously in 28-day cycles. The primary endpoint was anti-tumor activity. Results: As of July 17, 2023, 46 patients (32 patients with NRASmutations in Cohort 1 and 14 patients with NF1mutations in Cohort 2) were enrolled and received 12 mg FCN-159 QD. The median follow-up time was 8.6 months. Among 25 patients who failed in previous anti-PD-1 therapy in Cohort 1, 6 had confirmed partial responses (ORR, 24.0%; 95% confidence interval [CI], 9.4–45.1). Median DOR was 6.5 months (95% CI, 2.7–NE). Median progression-free survival (mPFS) was 3.6 months (95% CI, 1.8–5.5). Among 14 patients in Cohort 2, 1 had PR (ORR, 7.1%; 95% CI, 0.2-33.9) and mPFS was 2.8 months (95% CI, 1.8-5.5) (Table). Grade≥3 FCN-159-related treatment-emergent adverse events (TEAEs) were reported in 10 (21.7%) patients in both cohorts; the most common was blood creatine phosphokinase increased (13.0%). FCN-159–related serious AEs (SAEs) were reported in 3 (6.5%) patients, which were edema lower limb, cellulitis and pneumonia. Two (4.3%) patients discontinued treatment due to FCN-159 related TEAEs, including serous retinal detachment and herpes zoster. No FCN-159-related TEAEs led to death. Conclusions: FCN-159 showed encouraging efficacy data with well tolerated safety profile in patients with NRAS-mutant advanced melanoma, especially those who failed in previous anti-PD-1 therapy. Clinical trial information: NCT03932253.
| Confirmed best overall response. | ||||
|---|---|---|---|---|
| Cohort 1 | Cohort 1 | Cohort 2 | Total | |
| NRAS-Mutant (n = 32) | NRAS-Mutant and Failed in Previous Anti-PD-1 (n=25) | NF1-Mutant (n = 14) | (N = 46) | |
| Confirmed BOR, n (%) | ||||
| CR | 0 | 0 | 0 | 0 |
| PR | 6 (18.8) | 6 (24.0) | 1 (7.1) | 7 (15.2) |
| SD | 14 (43.8) | 9 (36.0) | 6 (42.9) | 20 (43.5) |
| PD | 10 (31.3) | 8 (32.0) | 6 (42.9) | 16 (34.8) |
| NE | 2 (6.3) | 2 (8.0) | 1 (7.1) | 3 (6.5) |
| ORR, n (%), 95% CI | 6 (18.8), 7.2–36.4 | 6 (24.0), 9.4-45.1 | 1 (7.1), 0.2–33.9 | 7 (15.2), 6.3–28.9 |
| CBR, n (%), 95% CI | 20 (62.5), 43.7–78.9 | 15 (60.0) 38.7-78.9 | 7 (50.0), 23.0–77.0 | 27 (58.7), 43.2–73.0 |
| Median DOR (95% CI), months | 6.5 (2.7–NE) | 6.5 (2.7-NE) | NR (NE–NE) | 6.5 (2.7–NE) |
| Median PFS (95% CI), months | 3.7 (1.8-5.5) | 3.6 (1.8-5.5) | 2.8 (1.8-5.5) | 3.6 (1.9-3.8) |
| Median OS (95% CI), months | 11.5 (8.2-NE) | 12.7 (7.6-NE) | NR (4.1-NE) | 12.7 (8.3-NE) |
NE, not evaluable; NR, not reached.
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Abstract Details
Session Type
Poster Session
Session Title
Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
Track
Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
Sub Track
Small Molecules
Clinical Trial Registration Number
NCT03932253
Citation
J Clin Oncol 42, 2024 (suppl 16; abstr 3095)
DOI
10.1200/JCO.2024.42.16_suppl.3095
Abstract #
3095
Poster Bd #
240
Abstract Disclosures
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