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Therapy Name | LXH 254 + Trametinib |
Synonyms | |
Therapy Description | |
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
---|---|---|---|---|
LXH 254 | LXH254|LXH-254|Naporafenib | BRAF Inhibitor 25 CRAF Inhibitor 12 | LXH 254 is a RAF inhibitor that selectively inhibits monomeric and dimerized BRAF and CRAF, which may lead to anti-tumor activity in RAF-mutant tumors and better tolerability (AACR Annual Meeting 2019, Abstract LB-114, PMID: 31059256). | |
Trametinib | Mekinist | GSK1120212 | MEK inhibitor (Pan) 26 MEK1 Inhibitor 26 MEK2 Inhibitor 24 | Mekinist (trametinib) inhibits MEK 1 and 2, which potentially leads to reduced tumor cell proliferation (PMID: 27956260). Mekinist (trametinib) is FDA approved for melanoma patients harboring BRAF V600E or BRAF V600K mutations, and in combination with Tafinlar (dabrafenib) for BRAF V600E/K-mutant melanoma, BRAF V600E- mutant non-small cell lung cancer, BRAF V600E-mutant anaplastic thyroid cancer, for adult and pediatric patients of 6 years or older with unresectable or metastatic solid tumors harboring BRAF V600E, and for pediatric patients of 1 year or older with low-grade glioma harboring BRAF V600E (FDA.gov). |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF N486_P490del | ovarian cancer | predicted - sensitive | LXH 254 + Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, combination of Mekinist (trametinib) and LXH 254 resulted in enhanced inhibition of metabolic activity in an ovarian cancer cell line harboring BRAF N486_P490del in culture (PMID: 37656784). | 37656784 |
BRAF L485_P490delinsY | lung non-small cell carcinoma | predicted - sensitive | LXH 254 + Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, combination of Mekinist (trametinib) and LXH 254 resulted in enhanced inhibition of metabolic activity in a non-small cell lung cancer cell line harboring BRAF L485_P490delinsY in culture (PMID: 37656784). | 37656784 |
BRAF V487_P492delinsA | pancreatic carcinoma | predicted - sensitive | LXH 254 + Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, combination of Mekinist (trametinib) and LXH 254 resulted in enhanced inhibition of metabolic activity in a pancreatic carcinoma cell line harboring BRAF V487_P492delinsA in culture (PMID: 37656784). | 37656784 |
NRAS mutant | melanoma | predicted - sensitive | LXH 254 + Trametinib | Phase I | Actionable | In a Phase Ib trial, treatment with the combination of LXH 254 and Mekinist (trametinib) demonstrated safety and resulted in an overall response rate of 30% (9/30, all partial responses), a disease control rate of 73.3% (22/30), with stable disease in 13 patients, and a median progression-free survival of 5.03 months in patients with melanoma harboring NRAS mutations (PMID: 36947734; NCT02974725). | 36947734 |
NRAS Q61R | urinary bladder cancer | sensitive | LXH 254 + Trametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, LXH 254 and Mekinist (trametinib) combination treatment decreased tumor volume and weight compared to vehicle in a cell line xenograft model of bladder cancer harboring NRAS Q61R (PMID: 34554931). | 34554931 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
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NCT06346067 | Phase III | LXH 254 + Trametinib Trametinib Dacarbazine Temozolomide | A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With NRAS-mutant Melanoma (SEACRAFT-2) | Recruiting | USA | NLD | GBR | FRA | ESP | CZE | CAN | AUS | 0 |
NCT05907304 | Phase I | LXH 254 + Trametinib | A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With RAS Q61X Mutations (SEACRAFT-1) | Recruiting | USA | GBR | CAN | AUS | 1 |
NCT02974725 | Phase I | LXH 254 + Ribociclib LXH 254 + Trametinib LTT462 + LXH 254 | A Phase Ib Study of LXH254-centric Combinations in NSCLC or Melanoma | Terminated | USA | SWE | POL | ITA | ISR | FRA | ESP | DEU | BEL | AUS | 1 |