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Therapy Name | PLX8394 |
Synonyms | |
Therapy Description |
PLX8394 is a RAF inhibitor that inhibits wild-type and mutant BRAF, as well as CRAF, and does not paradoxically activate MAPK signaling, potentially resulting in decreased proliferation of BRAF-mutant tumor cells (PMID: 26466569, PMID: 24283590, PMID: 28659148, PMID: 30559419). |
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
---|---|---|---|---|
PLX8394 | PLX 8394|PLX-8394|FORE8394|FORE-8394|FORE 8394|Plixorafenib | BRAF Inhibitor 25 CRAF Inhibitor 12 | PLX8394 is a RAF inhibitor that inhibits wild-type and mutant BRAF, as well as CRAF, and does not paradoxically activate MAPK signaling, potentially resulting in decreased proliferation of BRAF-mutant tumor cells (PMID: 26466569, PMID: 24283590, PMID: 28659148, PMID: 30559419). |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF V600E | Advanced Solid Tumor | sensitive | PLX8394 | Preclinical | Actionable | In a preclinical study, PLX8394 had been shown to block survival and growth of vemurafenib/PLX4720-resistant cells harboring distinct BRAF V600E splice variants (PMID: 24422853). | 24422853 |
BRAF G466V | lung cancer | predicted - sensitive | PLX8394 | Preclinical - Cell culture | Actionable | In a preclinical study, lung cancer cells harboring BRAF G466V demonstrated sensitivity to PLX8394 treatment in culture (PMID: 30559419). | 30559419 |
BRAF G469A | melanoma | sensitive | PLX8394 | Preclinical - Cell culture | Actionable | In a preclinical study, PLX8394 treatment inhibited Erk signaling and reduced proliferation of melanoma cells harboring BRAF G469A in culture (PMID: 30559419). | 30559419 |
BRAF G469A | lung adenocarcinoma | sensitive | PLX8394 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PLX8394 decreased growth of lung adenocarcinoma cell lines harboring BRAF G469A in culture, and reduced tumor growth in xenograft models (PMID: 27834212). | 27834212 |
BRAF L597R | prostate cancer | sensitive | PLX8394 | Preclinical - Cell culture | Actionable | In a preclinical study, PLX8394 treatment inhibited Erk signaling and reduced proliferation of prostate cancer cells harboring BRAF L597R in culture (PMID: 30559419). | 30559419 |
NRAS Q61R | melanoma | resistant | PLX8394 | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring NRAS Q61R demonstrated resistance to PLX8394 treatment in culture (PMID: 30559419). | 30559419 |
BRAF V600E BRAF over exp | melanoma | sensitive | PLX8394 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PLX8394 treatment inhibited Erk signaling and reduced tumor growth in a Zelboraf (vemurafenib)-resistant cell line xenograft model of melanoma overexpressing BRAF V600E (PMID: 30559419). | 30559419 |
BRAF G596R | colorectal cancer | predicted - sensitive | PLX8394 | Preclinical - Cell culture | Actionable | In a preclinical study, colorectal cancer cells harboring BRAF G596R demonstrated sensitivity to PLX8394 treatment in culture (PMID: 30559419). | 30559419 |
BRAF L485F | Advanced Solid Tumor | predicted - resistant | PLX8394 | Preclinical - Biochemical | Actionable | In a preclinical study, cells expressing BRAF L485F were resistant to treatment with PLX8394 in culture (PMID: 34108213). | 34108213 |
BRAF G466V | lung adenocarcinoma | sensitive | PLX8394 | Preclinical - Cell culture | Actionable | In a preclinical study, PLX8394 decreased growth of lung adenocarcinoma cell lines harboring BRAF G466V in culture (PMID: 27834212). | 27834212 |
BRAF L505H | Advanced Solid Tumor | predicted - resistant | PLX8394 | Preclinical - Biochemical | Actionable | In a preclinical study, cells expressing BRAF L505H were resistant to treatment with PLX8394 in culture (PMID: 34108213). | 34108213 |
BRAF act mut | Advanced Solid Tumor | sensitive | PLX8394 | Preclinical | Actionable | In a preclinical study, PLX8394 had been shown to block survival and growth of vemurafenib/PLX4720-resistant cells harboring distinct BRAF activating mutations (PMID: 24422853). | 24422853 |
BRAF mutant | melanoma | sensitive | PLX8394 | Preclinical | Actionable | In a preclinical study, PLX8394 blocked survival and growth of vemurafenib/PLX4720-resistant melanoma cells harboring BRAF V600E splice variants in culture (PMID: 24422853). | 24422853 |
BRAF V600E | glioblastoma | predicted - sensitive | PLX8394 | Case Reports/Case Series | Actionable | In a clinical case study, PLX8394 treatment resulted in a radiographic partial response and complete resolution of symptoms for 7 months in a patient with glioblastoma harboring BRAF V600E, CDKN2A/B loss and CHEK2 T367fs were also identified in the tumor (PMID: 32923904; NCT02428712). | 32923904 |
BRAF V504_R506dup | Advanced Solid Tumor | resistant | PLX8394 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, cells expressing BRAF V504_R506dup were resistant to treatment with PLX8394 in culture and cell line xenograft models (PMID: 34108213). | 34108213 |
BRAF V600X | Advanced Solid Tumor | predicted - sensitive | PLX8394 | Phase Ib/II | Actionable | In a Phase I/II trial, PLX8394 treatment resulted in a partial response in 39% (9/23) of patients with MAPK inhibitor-naive advanced solid tumors (excluding colorectal cancer) harboring BRAF V600X with a median duration of response of 32 months, and resulted in a partial response in 18% (3/17) and stable disease in 29% of patients previously treated with a MAPK inhibitor (J Clin Oncol 41, 2023 (suppl 16; abstr 3006); NCT02428712). | detail... |
NRAS Q61K | melanoma | resistant | PLX8394 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PLX8394 treatment did not inhibit Erk signaling or reduce tumor growth in a Zelboraf (vemurafenib)-resistant cell line xenograft model of melanoma harboring NRAS Q61K (PMID: 30559419). | 30559419 |
BRAF fusion | Advanced Solid Tumor | predicted - sensitive | PLX8394 | Phase Ib/II | Actionable | In a Phase I/II trial, PLX8394 treatment resulted in stable disease in 46% of patients with advanced solid tumors harboring BRAF fusions and a complete response with a duration of response of at least 51.8 months in a patient with melanoma harboring AGK-BRAF (J Clin Oncol 41, 2023 (suppl 16; abstr 3006); NCT02428712). | detail... |
BRAF V600K | colon cancer | sensitive | PLX8394 | Preclinical - Cell culture | Actionable | In a preclinical study, PLX8394 treatment inhibited Erk signaling and reduced proliferation of colon cancer cells harboring BRAF V600K in culture (PMID: 30559419). | 30559419 |
BRAF L514V BRAF V600E | melanoma | decreased response | PLX8394 | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells expressing BRAF L514V in cis with V600E demonstrated decreased response to PLX8394-induced inhibition of Erk phosphorylation and colony formation compared to cells expressing BRAF V600E in culture (PMID: 29880583). | 29880583 |
BRAF R506_K507insLLR | Advanced Solid Tumor | resistant | PLX8394 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, cells expressing BRAF R506_K507insLLR were resistant to treatment with PLX8394 in culture and cell line xenograft models (PMID: 34108213). | 34108213 |
BRAF V600E | melanoma | sensitive | PLX8394 | Preclinical - Cell culture | Actionable | In a preclinical study, PLX8394 treatment inhibited Erk phosphorylation and reduced proliferation of melanoma cells harboring either monomeric BRAF V600E or dimeric isoform (p61) of V600E in culture (PMID: 30559419). | 30559419 |
BRAF K601E | colorectal cancer | predicted - sensitive | PLX8394 | Preclinical - Pdx | Actionable | In a preclinical study, PLX8394 treatment resulted in partial inhibition of tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF K601E (PMID: 30559419). | 30559419 |
BRAF K601N | chronic lymphocytic leukemia | sensitive | PLX8394 | Preclinical - Cell culture | Actionable | In a preclinical study, PLX8394 treatment inhibited Erk signaling and reduced proliferation of chronic lymphocytic leukemia cells harboring BRAF K601N in culture (PMID: 30559419). | 30559419 |
BRAF G466V | colorectal cancer | resistant | PLX8394 | Preclinical - Pdx | Actionable | In a preclinical study, PLX8394 treatment did not inhibit Erk signaling or reduce tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF G466V (PMID: 30559419). | 30559419 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
---|---|---|---|---|---|---|
NCT05503797 | Phase II | Cobicistat + PLX8394 PLX8394 | A Study to Assess the Efficacy and Safety of FORE8394 in Participants With Cancer Harboring BRAF Alterations | Recruiting | USA | SWE | ITA | GBR | FRA | ESP | DEU | CAN | 1 |
NCT02428712 | Phase Ib/II | PLX8394 | A Study of FORE8394 as a Single Agent in Patients With Advanced Unresectable Solid Tumors | Completed | USA | 0 |
NCT06610682 | Phase I | PLX8394 | Feasibility of CSF and Plasma ctDNA in BRAF-altered Glioma During Treatment With Plixorafenib | Not yet recruiting | USA | 0 |
NCT02012231 | Phase Ib/II | PLX8394 | Phase I/IIa Study to Evaluate the Safety, PK, PD, and Preliminary Efficacy of PLX8394 in Patients With Advanced Cancers. | Terminated | USA | 0 |