Therapy Detail

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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).

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Drug Name Trade Name Synonyms Drug Classes Drug Description
PLX8394 PLX 8394|PLX-8394|FORE8394|FORE-8394|FORE 8394 BRAF Inhibitor 21 CRAF Inhibitor 11 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).

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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 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 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 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 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
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 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 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 V600X Advanced Solid Tumor predicted - sensitive PLX8394 Phase Ib/II Actionable In a Phase I/IIa trial, PLX8394 resulted in an objective response rate of 20.8% and a clinical benefit rate (CBR) of 35.4% at 24 weeks in advanced solid tumor patients harboring BRAF V600X, and in patients with no prior BRAF/MEK inhibitor therapy (excluding colorectal cancer), resulted in 31.6% (6/19) confirmed partial responses, a CBR of 63.2% (12/19), a median response time of 12.1 weeks, and a median response duration of 13.5 mo (Ann Oncol (2022) 33 (suppl_7): S197-S224; 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 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 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
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 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 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 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 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 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 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
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 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 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 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 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

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Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries
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
NCT02428712 Phase Ib/II PLX8394 A Study of FORE8394 as a Single Agent in Patients With Advanced Unresectable Solid Tumors Recruiting USA 0


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