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    DRUG:

    naporafenib (ERAS-254)

    i
    Other names: ERAS-254, LXH254, LXH 254, LXH-254, ERAS 254, ERAS254
    Company:
    Erasca, Novartis
    Drug class:
    BRAF inhibitor, pan-RAF inhibitor, cRAF inhibitor
    Related drugs:
    1m
    Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma (clinicaltrials.gov)
    P2, N=134, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Oct 2025 --> Mar 2026 | Trial primary completion date: Oct 2025 --> Mar 2026
    Trial completion date • Trial primary completion date
    |
    BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    NRAS mutation • BRAF V600
    |
    Mekinist (trametinib) • Kisqali (ribociclib) • naporafenib (ERAS-254) • rineterkib (LTT462)
    3ms
    Study of EGF816 in Combination With Selected Targeted Agents in EGFR-mutant NSCLC (clinicaltrials.gov)
    P1, N=105, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Oct 2025 --> Mar 2026 | Trial primary completion date: Oct 2025 --> Mar 2026
    Trial completion date • Trial primary completion date
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR exon 20 insertion • EGFR exon 20 mutation
    |
    Mekinist (trametinib) • gefitinib • Kisqali (ribociclib) • Tabrecta (capmatinib) • naporafenib (ERAS-254) • nazartinib (EGF816)
    4ms
    Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma (clinicaltrials.gov)
    P2, N=134, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jul 2025 --> Oct 2025 | Trial primary completion date: Jun 2025 --> Oct 2025
    Trial completion date • Trial primary completion date
    |
    BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    NRAS mutation • BRAF V600
    |
    Mekinist (trametinib) • Kisqali (ribociclib) • naporafenib (ERAS-254) • rineterkib (LTT462)
    7ms
    SEACRAFT-1: A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With RAS Q61X Mutations (clinicaltrials.gov)
    P1, N=86, Active, not recruiting, Erasca, Inc. | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    RAS mutation
    |
    Mekinist (trametinib) • naporafenib (ERAS-254)
    7ms
    Targeting the MAPK Pathway for NRAS Mutant Melanoma: From Mechanism to Clinic. (PubMed, Br J Dermatol)
    In recent years, significant clinical advancements have been achieved by targeting the NRAS-MAPK pathway, with novel therapies such as the MEK inhibitor tunlametinib and the combination therapy of the pan-RAF inhibitor naporafenib with trametinib leading the way. In this review, we will systematically summarize the recent advances in the direct targeting of mutant NRAS proteins and their downstream RAF and MEK proteins, as well as targeting the MAPK pathway in combination with other therapeutic targets, including the immunotherapy, to treat NRAS mutant melanoma. Additionally, we will further discuss the current issues and emerging countermeasures related to targeted therapy for NRAS mutant melanoma.
    Journal • IO biomarker
    |
    NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    NRAS mutation
    |
    Mekinist (trametinib) • Kolupin (tunlametinib) • naporafenib (ERAS-254)
    8ms
    Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma (clinicaltrials.gov)
    P2, N=134, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Mar 2025 --> Jul 2025 | Trial primary completion date: Feb 2025 --> Jun 2025
    Trial completion date • Trial primary completion date
    |
    BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    NRAS mutation • BRAF V600
    |
    Mekinist (trametinib) • Kisqali (ribociclib) • naporafenib (ERAS-254) • rineterkib (LTT462)
    9ms
    Study of EGF816 in Combination With Selected Targeted Agents in EGFR-mutant NSCLC (clinicaltrials.gov)
    P1, N=105, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Apr 2025 --> Oct 2025 | Trial primary completion date: Apr 2025 --> Oct 2025
    Trial completion date • Trial primary completion date
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR exon 20 insertion • EGFR exon 20 mutation
    |
    Mekinist (trametinib) • gefitinib • Kisqali (ribociclib) • Tabrecta (capmatinib) • naporafenib (ERAS-254) • nazartinib (EGF816)
    12ms
    Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma (clinicaltrials.gov)
    P2, N=134, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Dec 2024 --> Mar 2025
    Trial completion date • Metastases
    |
    BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    NRAS mutation • BRAF V600
    |
    Mekinist (trametinib) • Kisqali (ribociclib) • naporafenib (ERAS-254) • rineterkib (LTT462)
    1year
    A Study of Select Drug Combinations in Adult Patients With Advanced/Metastatic BRAF V600 Colorectal Cancer (clinicaltrials.gov)
    P1, N=122, Terminated, Novartis Pharmaceuticals | Trial completion date: Jan 2025 --> Sep 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Jan 2025 --> Sep 2024; The decision of early termination was made due to business reasons, and was not based on any safety concerns for any of the treatment combinations.
    Trial completion date • Trial termination • Trial primary completion date
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF mutation • BRAF V600
    |
    Mekinist (trametinib) • Tafinlar (dabrafenib) • Tevimbra (tislelizumab-jsgr) • spartalizumab (PDR001) • naporafenib (ERAS-254) • batoprotafib (TNO155) • rineterkib (LTT462)
    1year
    A phase Ib study of the combination of naporafenib with rineterkib or trametinib in patients with advanced and metastatic KRAS- or BRAF-mutant non-small cell lung cancer. (PubMed, Lung Cancer)
    Both naporafenib combinations had acceptable safety profiles. Antitumor activity was limited in patients with NSCLC, despite the observed on-target pharmacodynamic effect.
    P1 data • Journal • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • DUSP6 (Dual specificity phosphatase 6)
    |
    KRAS mutation • BRAF mutation • NRAS mutation
    |
    Mekinist (trametinib) • naporafenib (ERAS-254) • rineterkib (LTT462)
    1year
    Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma (clinicaltrials.gov)
    P2, N=134, Active, not recruiting, Novartis Pharmaceuticals | Trial primary completion date: Aug 2024 --> Nov 2024
    Trial primary completion date • Metastases
    |
    BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    NRAS mutation • BRAF V600
    |
    Mekinist (trametinib) • Kisqali (ribociclib) • naporafenib (ERAS-254) • rineterkib (LTT462)
    1year
    Study of EGF816 in Combination With Selected Targeted Agents in EGFR-mutant NSCLC (clinicaltrials.gov)
    P1, N=105, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Dec 2024 --> Apr 2025 | Trial primary completion date: Dec 2024 --> Apr 2025
    Trial completion date • Trial primary completion date • Combination therapy
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR exon 20 insertion • EGFR exon 20 mutation
    |
    Mekinist (trametinib) • gefitinib • Kisqali (ribociclib) • Tabrecta (capmatinib) • naporafenib (ERAS-254) • nazartinib (EGF816)