Therapy Detail

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Therapy Name LXH 254 + Trametinib
Synonyms
Therapy Description

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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) 24 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).

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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
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
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 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
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

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Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries
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
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 0
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 | ITA | FRA | ESP | DEU | BEL | AUS 4


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