Therapy Detail
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| Therapy Name | LXH 254 |
| Synonyms | |
| Therapy Description |
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). |
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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). |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| BRAF L485_P490delinsF | Advanced Solid Tumor | predicted - sensitive | LXH 254 | Preclinical - Biochemical | Actionable | In a preclinical study, LXH 254 inhibited Mek and Erk phosphorylation in cells expressing BRAF L485_P490delinsF in culture (PMID: 37656784). | 37656784 |
| BRAF mutant | Advanced Solid Tumor | predicted - sensitive | LXH 254 | Case Reports/Case Series | Actionable | In a Phase I trial, LXH 254 treatment resulted in partial response in 2.6% (2/75) and stable disease in 33% (25/75) of patients with advanced solid tumors harboring MAPK pathway alterations, one of the patient achieved partial response harbored a BRAF mutation (J Clin Oncol 36, no. 15_suppl (May 20 2018) 2586-2586; NCT02607813). | detail... |
| BRAF D287H NRAS Q61K | melanoma | predicted - sensitive | LXH 254 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a melanoma cell line harboring BRAF D287H and NRAS Q61K was sensitive to treatment with LXH254, demonstrating inhibition of cell proliferation in culture, and inhibition of tumor growth in a cell line xenograft model of melanoma (PMID: 33355204). | 33355204 |
| BRAF V487_P492delinsA | pancreatic carcinoma | sensitive | LXH 254 | Preclinical - Cell culture | Actionable | In a preclinical study, LXH 254 inhibited MAPK signaling and colony formation in a pancreatic carcinoma cell line harboring BRAF V487_P492delinsA in culture (PMID: 37656784). | 37656784 |
| BRAF G469A | lung adenocarcinoma | sensitive | LXH 254 | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF G469A were sensitive to treatment with LXH 254 in culture, demonstrating inhibition of cell growth (PMID: 32540409). | 32540409 |
| BRAF N486_P490del | pancreatic ductal adenocarcinoma | sensitive | LXH 254 | Preclinical - Patient cell culture | Actionable | In a preclinical study, LXH 254 inhibited growth of organoids derived from pancreatic ductal adenocarcinoma patients harboring BRAF N486_P490del in culture (PMID: 37656784). | 37656784 |
| BRAF L597V | lung adenocarcinoma | sensitive | LXH 254 | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were sensitive to treatment with LXH 254 in culture, demonstrating inhibition of cell growth (PMID: 32540409). | 32540409 |
| BRAF N486_P490del | ovarian cancer | sensitive | LXH 254 | Preclinical - Cell culture | Actionable | In a preclinical study, LXH 254 inhibited MAPK signaling and colony formation in an ovarian cancer cell line harboring BRAF N486_P490del in culture (PMID: 37656784). | 37656784 |
| BRAF V487_P492delinsA | Advanced Solid Tumor | predicted - sensitive | LXH 254 | Preclinical - Biochemical | Actionable | In a preclinical study, LXH 254 inhibited Mek and Erk phosphorylation in cells expressing BRAF V487_P492delinsA in culture (PMID: 37656784). | 37656784 |
| BRAF L485_P490delinsFS | Advanced Solid Tumor | predicted - sensitive | LXH 254 | Preclinical - Biochemical | Actionable | In a preclinical study, LXH 254 inhibited Mek and Erk phosphorylation in cells expressing BRAF L485_P490delinsFS in culture (PMID: 37656784). | 37656784 |
| BRAF V600E | melanoma | predicted - sensitive | LXH 254 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E was sensitive to treatment with LXH254, demonstrating inhibition of cell proliferation in culture, and inhibition of tumor growth and tumor regression in a cell line xenograft model of melanoma (PMID: 33355204). | 33355204 |
| NRAS Q61R | urinary bladder cancer | sensitive | LXH 254 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, LXH 254 treatment decreased Mek signaling, colony formation and viability, and increased apoptosis in a bladder cancer cell line harboring NRAS Q61R in culture and decreased tumor weight and volume in a cell line xenograft model (PMID: 34554931). | 34554931 |
| BRAF L485_P490delinsY | Advanced Solid Tumor | predicted - sensitive | LXH 254 | Preclinical - Biochemical | Actionable | In a preclinical study, LXH 254 inhibited Mek and Erk phosphorylation in cells expressing BRAF L485_P490delinsY in culture (PMID: 37656784). | 37656784 |
| HRAS G12V | urinary bladder cancer | sensitive | LXH 254 | Preclinical - Cell culture | Actionable | In a preclinical study, LXH 254 treatment decreased viability of a bladder cancer cell line harboring HRAS G12V in culture (PMID: 34554931). | 34554931 |
| BRAF L485_T488delinsF | Advanced Solid Tumor | predicted - sensitive | LXH 254 | Preclinical - Biochemical | Actionable | In a preclinical study, LXH 254 inhibited ERK and MEK signaling in cells expressing BRAF L485_T488delinsF in culture (PMID: 37656784). | 37656784 |
| BRAF N486_P490del | Advanced Solid Tumor | predicted - sensitive | LXH 254 | Preclinical - Biochemical | Actionable | In a preclinical study, LXH 254 inhibited Mek and Erk phosphorylation in cells expressing BRAF N486_P490del in culture (PMID: 37656784). | 37656784 |
| BRAF loss NRAS Q61K | melanoma | decreased response | LXH 254 | Preclinical - Cell culture | Actionable | In a preclinical study, CRISPR-Cas9 mediated knockout of BRAF in a melanoma cell line harboring NRAS Q61K led to decreased sensitivity to LXH254 treatment compared to parental cells harboring BRAF D287H and NRAS Q61K in culture (PMID: 33355204). | 33355204 |
| BRAF L485_P490delinsY | lung non-small cell carcinoma | sensitive | LXH 254 | Preclinical - Cell culture | Actionable | In a preclinical study, LXH 254 inhibited MAPK signaling and colony formation in a non-small cell lung cancer cell line harboring BRAF L485_P490delinsY in culture (PMID: 37656784). | 37656784 |
Filtering
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- Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
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- Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")
Sorting
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- Click on any column header arrows to sort by that column
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| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|---|---|---|---|---|---|
| NCT02607813 | Phase I | LXH 254 + Spartalizumab LXH 254 | Phase I Study of LXH254 in Patients With Advanced Solid Tumors Haboring MAPK Pathway Alterations | Terminated | USA | NLD | ITA | FRA | ESP | DEU | CAN | 3 |
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