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    Association details:
    Biomarker:NRAS mutation
    Cancer:Melanoma
    Drug:Mekinist (trametinib) (MEK inhibitor)
    Direction:Sensitive
    Evidence:
    Evidence Level:
    Sensitive: C2 – Inclusion Criteria
    Source:
    clinicaltrials.gov
    Title:

    A Phase 1B Clinical Trial of Trametinib Plus Digoxin in Patients With Unresectable or Metastatic BRAF Wild-type Melanoma

    Excerpt:
    ...BRAF wild-type confirmed, and NRAS mutation assessed....
    Trial ID:
    NCT02138292
    Evidence Level:
    Sensitive: C2 – Inclusion Criteria
    Source:
    clinicaltrials.gov
    Title:

    MEK and Autophagy Inhibition in Metastatic/Locally Advanced, Unresectable Neuroblastoma RAS (NRAS) Melanoma

    Excerpt:
    ...Histologically confirmed metastatic or locally advanced unresectable malignant melanoma with an activating NRAS mutation....
    Trial ID:
    CHLOROTRAMMEL
    More C2 evidence
    Evidence Level:
    Sensitive: C2 – Inclusion Criteria
    Source:
    clinicaltrialsregister.eu
    Title:

    MEK and Autophagy Inhibition in Metastatic/Locally Advanced, Unresectable NRAS Melanoma: A Phase Ib/II Trial of Trametinib plus Hydroxychloroquine in Patients with NRAS Melanoma. CHLORO TRAM MEL Etude de phase I/II évaluant la tolérance d’un traitement par hydroxychloroquine associé au tramétinib dans le mélanome NRAS muté métastatique ou localement avancé non résécable après échec d’une immunothérapie. CHLORO TRAM MEL

    Excerpt:
    ...Histologically confirmed metastatic or locally advanced unresectable malignant melanoma with an activating NRAS mutation.2. ...
    Trial ID:
    2019-001399-13
    Less C2 evidence
    Evidence Level:
    Sensitive: C3 – Early Trials
    Source:
    Eur J Cancer
    Title:

    PACMEL: A phase 1 dose escalation trial of trametinib (GSK1120212) in combination with paclitaxel

    Excerpt:
    Six (40%) partial responses were reported, including four of eight patients with NRAS mutations. Median progression free survival was 5.5 months (95% confidence interval (CI) 1.8-7.8 months) and overall survival, 14.1 months....Trametinib can safely be given with weekly paclitaxel at the full monotherapy dose.
    DOI:
    10.1016/j.ejca.2014.11.018
    Evidence Level:
    Sensitive: C3 – Early Trials
    Source:
    Lancet Oncol
    Title:

    Activity of the MEK Inhibitor Trametinib (GSK1120212) in Advanced Melanoma in a Phase I, Dose-escalation Trial

    Excerpt:
    The best response observed in seven patients with an NRAS mutation was SD (n=2), one of whom received treatment for 48 weeks.
    DOI:
    10.1016/S1470-2045(12)70269-3
    Trial ID:
    NCT00687622
    Evidence Level:
    Sensitive: D – Preclinical
    Source:
    Pediatr Blood Cancer
    Title:

    Combinatorial effects of azacitidine and trametinib on NRAS-mutated melanoma

    Published date:
    12/06/2021
    Excerpt:
    Correspondingly, concomitant exposure to trametinib and azacitidine prevented development of trametinib resistance in NRAS-mutated human melanoma cells in vitro....These observations suggest that azacitidine enhances trametinib monotherapy and may represent a promising candidate drug for combination therapies to enhance the efficacy of MEK inhibitors in RAS-driven diseases.
    Secondary therapy:
    azacitidine
    DOI:
    10.1002/pbc.29468
    Evidence Level:
    Sensitive: D – Preclinical
    Source:
    Cancer Res
    Title:

    A Functional Landscape of Resistance to MEK1/2 and CDK4/6 Inhibition in NRAS-Mutant Melanoma

    Excerpt:
    NRAS-mutant melanoma cell lines are NRAS-dependent and sensitive to trametinib and palbociclib….NRAS mutant melanoma cell line sensitivity, after 72 and 144 hours, to each single agent varied ranging from 1 to 10 nmol/L GI50 for trametinib and 1 to 10 μmol/L GI50 for palbociclib (Supplementary Fig. S1E).
    DOI:
    10.1158/0008-5472.CAN-18-2711