^
    3d
    IM-BATTLE-2 Program: Trametinib and Pembrolizumab in Treating Patients With Recurrent Non-small Cell Lung Cancer That Is Metastatic, Unresectable, or Locally Advanced (clinicaltrials.gov)
    P1/2, N=37, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027
    Trial completion date • Trial primary completion date
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    ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4)
    |
    EGFR T790M • ALK fusion
    |
    Keytruda (pembrolizumab) • Mekinist (trametinib)
    3d
    MIRV: Phase 1/2 Study of Mirdametinib + Vinblastine for Newly Diagnosed/Previously Untreated PLGG + Activation of MAPK (clinicaltrials.gov)
    P1/2, N=50, Recruiting, St. Justine's Hospital | Not yet recruiting --> Recruiting
    Enrollment open
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    BRAF (B-raf proto-oncogene) • NF1 (Neurofibromin 1) • KIAA1549
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    BRAF V600E • BRAF V600 • BRAF fusion
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    Gomekli (mirdametinib) • vinblastine
    4d
    Exploratory Analysis of Biomarkers and Treatment Outcomes From the COLUMBUS Study in BRAF V600E/K-Mutant Advanced or Metastatic Melanoma. (PubMed, Clin Cancer Res)
    The greatest benefits of encorafenib plus binimetinib were observed in patients with evidence of high TMB and/or tumor immune infiltration, suggesting potential immune contributions to efficacy, which were not observed with vemurafenib. BRAF V600 detectability in ctDNA appears to have utility as a marker of prognosis and response in this population.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • IFNG (Interferon, gamma)
    |
    PD-L1 expression • BRAF V600E • TMB-H • BRAF V600 • BRAF V600K
    |
    Zelboraf (vemurafenib) • Mektovi (binimetinib) • Braftovi (encorafenib)
    5d
    Tumor-Macrophage-Nerve interactions drive neuroinflammation and neuropathic pain in prostate cancer perineural invasion. (PubMed, Brain Behav Immun)
    This model provides insight into neuroinflammatory tumor-macrophage-nerve interactions associated with neuronal hyperexcitability. Although focused in scope, it enables stepwise investigation of tumor-induced neuronal responses and offers a useful platform for evaluating neuroinflammatory mechanisms of tumor invasion and for identifying potential therapeutic targets.
    Journal
    |
    TNFA (Tumor Necrosis Factor-Alpha) • TIMP1 (Tissue inhibitor of metalloproteinases 1) • IL1B (Interleukin 1, beta) • IL1R1 (Interleukin 1 receptor, type I)
    |
    PD98059
    6d
    NCI-2013-02103: Testing the Addition of Navitoclax to the Combination of Dabrafenib and Trametinib in People Who Have BRAF Mutant Melanoma (clinicaltrials.gov)
    P1/2, N=75, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027
    Trial completion date • Trial primary completion date • IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2)
    |
    BRAF V600E • BRAF V600 • BRAF V600K
    |
    THXID® BRAF Kit • cobas® 4800 BRAF V600 Mutation Test
    |
    Mekinist (trametinib) • Tafinlar (dabrafenib) • navitoclax (ABT 263) • omipalisib (GSK2126458)
    7d
    RAMP 203: Phase 1/2 Study of Avutometinib (VS-6766) + Sotorasib With or Without Defactinib in KRAS G12C NSCLC Patients (clinicaltrials.gov)
    P1/2, N=153, Active, not recruiting, Verastem, Inc. | Recruiting --> Active, not recruiting | Trial primary completion date: Sep 2025 --> Jun 2026
    Enrollment closed • Trial primary completion date
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Lumakras (sotorasib) • Avmapki (avutometinib) • Fakzynja (defactinib)
    7d
    Panitumumab With or Without Trametinib in Treating Patients With Stage IV Colorectal Cancer (clinicaltrials.gov)
    P2, N=59, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2026 --> Jan 2027
    Trial completion date • Trial primary completion date
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MAP2K1 (Mitogen-activated protein kinase kinase 1)
    |
    KRAS mutation • BRAF mutation • NRAS mutation • KRAS wild-type • RAS wild-type • NRAS wild-type
    |
    Mekinist (trametinib) • Vectibix (panitumumab)
    8d
    NCI-2018-01218: Neratinib and Everolimus, Palbociclib, or Trametinib in Treating Participants With Refractory and Advanced or Metastatic Solid Tumors With EGFR Mutation/Amplification, HER2 Mutation/Amplification, or HER3/4 Mutation or KRAS Mutation (clinicaltrials.gov)
    P1, N=93, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Oct 2025 --> Oct 2028 | Trial primary completion date: Oct 2025 --> Oct 2028
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • ERBB4 (erb-b2 receptor tyrosine kinase 4)
    |
    KRAS mutation • EGFR mutation • HER-2 amplification • EGFR amplification
    |
    Mekinist (trametinib) • Ibrance (palbociclib) • everolimus • Nerlynx (neratinib)
    8d
    RAS/MEK/PI3K pathway inhibition augments response to CD40 agonism by targeting CD11b+ Bregs thereby overcoming melanoma PD1-resistance. (PubMed, Nat Commun)
    Here, we show that combined treatment with a RAS/PI3K/AKT-pathway inhibitor rigosertib (RGS), and/or a MEK1/2 inhibitor trametinib (T), plus aCD40, overcomes the ICB resistance of BRAFwtNRASwt and BRAFwtNRASmut melanoma tumors growing in C57BL/6 mice. scRNA-Seq analyses confirm CD40-associated CD11b+ Bregs across cancer types in patients. Our data demonstrate that addition of RAS/PI3K/AKT and MEK inhibitors to aCD40 resolves the issue of aCD40 induction of CD11b+PD-L1+ Bregs and provides alternative therapeutic options for ICB-resistant BRAFwtNRASwt or BRAFwtNRASmut metastatic melanoma.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • ITGAM (Integrin, alpha M) • CD40 (CD40 Molecule)
    |
    NRAS wild-type
    |
    Mekinist (trametinib) • Estybon (rigosertib)
    12d
    SARC031: A Phase 2 Trial of Selumetinib and Sirolimus for Patients with Unresectable or Metastatic Malignant Peripheral Nerve Sheath Tumors (MPNST). (PubMed, Clin Cancer Res)
    The combination was safe with manageable and expected AEs, but did not meet study parameters for further evaluation in MPNST. Correlative studies were informative and may guide future therapeutic trials of MPNST.
    P2 data • Journal
    |
    NF1 (Neurofibromin 1)
    |
    Koselugo (selumetinib) • sirolimus
    12d
    A Window of Opportunity Trial of Mirdametinib Plus Vorinostat for NF1 Associated, H3K27 Trimethylation Deficient Malignant Peripheral Nerve Sheath Tumor [MPNST] (clinicaltrials.gov)
    P1, N=8, Recruiting, University of Minnesota | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2026 --> Jan 2027
    Trial completion date • Trial primary completion date
    |
    Gomekli (mirdametinib) • Zolinza (vorinostat)