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
3628 - Predictive model for survival in advanced non-small-cell lung cancer (NSCLC) treated with frontline pembrolizumab
Presenter: Xabier Mielgo Rubio
Session: Poster Display session 3
Resources:
Abstract
5705 - External validation and longitudinal extension of the LIPI (Lung Immune Prognostic Index) for immunotherapy outcomes in advanced non-small cell lung cancer.
Presenter: Jakob Riedl
Session: Poster Display session 3
Resources:
Abstract
5758 - Changes of TCR Repertoire in Metastatic Renal Cell Carcinoma and Metastatic Melanoma Patients Treated with Nivolumab
Presenter: Martin Klabusay
Session: Poster Display session 3
Resources:
Abstract
1743 - Expression of MHC class I, HLA-A and HLA-B identifies immune activated breast tumors with favorable outcome
Presenter: María Del Mar Noblejas López
Session: Poster Display session 3
Resources:
Abstract
2219 - Prognostic Significance of Tumor Tissue NeuGcGM3 Ganglioside Expression and Predictive Value of Circulating Tumor Cell Count Monitoring in Patients Receiving Racotumomab Immunotherapy
Presenter: Necdet Üskent
Session: Poster Display session 3
Resources:
Abstract
2996 - Evolution of Myeloid-Derived Suppressor Cells and Objective Response Rate in Relapsed/Refractory Diffuse Large B Cell Lymphoma (R/R DLBCL) patients after receiving immunotherapy
Presenter: Carlos Jiménez Cortegana
Session: Poster Display session 3
Resources:
Abstract
2110 - A Phase Ia/Ib trial of the anti-programmed death-ligand 1 (PD-L1) human monoclonal antibody (mAb), CS1001, in patients (pts) with advanced solid tumors or lymphomas
Presenter: Lin Shen
Session: Poster Display session 3
Resources:
Abstract
3515 - Results from a randomised Phase 1/2 trial evaluating the safety and antitumour activity of anti-PD-1 (MEDI0680)/anti-PD-L1 (durvalumab) vs anti-PD-1 (nivolumab) alone in metastatic clear cell renal cell carcinoma (ccRCC)
Presenter: Martin Voss
Session: Poster Display session 3
Resources:
Abstract
3566 - Pembrolizumab in Advanced Rare Cancers
Presenter: Aung Naing
Session: Poster Display session 3
Resources:
Abstract
3567 - High clinical benefit rates of pembrolizumab in very rare sarcoma histotypes: first results of the AcSé Pembrolizumab study
Presenter: Jean-Yves Blay
Session: Poster Display session 3
Resources:
Abstract