Abstract 1832
Background
Gain of function mutations in NRAS occurs in 15-25% of patients with melanoma, leading to activation of Ras/Raf/MEK/ERK signaling pathway results in unconstrained cell growth and cell transformation. The MEK inhibitor targets this signaling pathway, inhibiting cell proliferation and inducing apoptosis. NRAS mutation status was identified as an independent poor prognostic factor in stage IV melanoma. It is also reported that the survival of patients with high copy number (>4) was significantly worse than that of NRAS patients with 2-4 copy number (P = 0.002). No drug was approved to treat melanoma patients with NRAS mutation or amplification until now. FCN-159, an oral and potent MEK1/2 inhibitor, has more than 10 folds higher selectivity against activated MEK1 and MEK2 compared with trametinib, and has demonstrated significant antitumor growth inhibition in two patient-derived xenograft (PDX) models with NRAS mutation. This is the first in human study to evaluate the safety and anti-tumor activity of FCN-159 in patients.
Trial design
This is a phase Ia/Ib, open label, dose-escalation study with expansion cohort that will evaluate the safety, pharmacokinetics (PK), and preliminary anti-tumor activity of FCN-159 in up to 37 patients with locally advanced or metastatic melanoma harboring NRAS-aberrant including both NRAS amplification and mutation (Ia) and NRAS-mutation only (Ib). In this study, the dose escalation utilizes 3 + 3, accelerated titration design with starting dose of 0.2 mg, QD, orally; the dose will be escalated until Maximum-Tolerated Dose (MTD) or the Recommended phase II dose (RP2D) being identified. The dose level will be considered to expand up to 6 patients if an objective response is observed, intending to collect more clinical data to support the RP2D determination. Once the MTD or RP2D is identified, an expansion cohort will be followed to further evaluate the safety and efficacy of FCN-159 in patients with NRAS-mutant melanoma. As of April 22, 2019, one patient has been dosed.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Shanghai Fosun Pharmaceutical Development Co, Ltd.
Funding
Shanghai Fosun Pharmaceutical Development Co, Ltd.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2927 - Singapore Caregiver Quality Of Life Scale (SCQOLS): Turkish Validity and Reliability Study
Presenter: Nur Basak
Session: Poster Display session 3
Resources:
Abstract
5066 - Screening for Psicosocial Distress in recently diagnosed cancer patients
Presenter: Eva Baillès
Session: Poster Display session 3
Resources:
Abstract
6074 - Socio-demographic characteristics and quality of life analysis of cancer survivors followed at a Primary Care Center.
Presenter: Begona Grana Suarez
Session: Poster Display session 3
Resources:
Abstract
5129 - The adhesion in the screening measures in carrying patients of breast cancer and ovary hereditary and the relationship with the psychological aspects
Presenter: Melinda Concepcion
Session: Poster Display session 3
Resources:
Abstract
5635 - Assessment of emotional discomfort of oncological patients in the first nursing visit at Donostia University Hospital
Presenter: Elena Uranga
Session: Poster Display session 3
Resources:
Abstract
858 - A systematic review and meta-analysis of the distress thermometer for the screening of distress in Chinese patients with cancer
Presenter: Hui Hui Sun
Session: Poster Display session 3
Resources:
Abstract
4475 - Pharmacist and Nurse (PN) Led Melanoma Immunotherapy Clinic: Patient Experience Survey
Presenter: Dharmisha Chauhan
Session: Poster Display session 3
Resources:
Abstract
1871 - Phone Triage & Acute Review Clinics: The emerging role of the Oncology Specialist Nurse
Presenter: Fiona Barrett
Session: Poster Display session 3
Resources:
Abstract
5193 - Patient reported outcomes during immunotherapy: symptom burden in daily clinical practice
Presenter: José Koldenhof
Session: Poster Display session 3
Resources:
Abstract
2453 - Factors related to hospital length of stay, re-admissions and unplanned care for patients with cancer, an on-going study
Presenter: Helena Ullgren
Session: Poster Display session 3
Resources:
Abstract