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Therapy Name	LY3214996
Synonyms
Therapy Description	LY3214996 inhibits ERK1/2, potentially resulting in decreased growth of tumors with alterations in the RAS/MAPK pathway (AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4973, PMID: 31744895).

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Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
LY3214996		Temuterkib\|LY-3214996\|LY 3214996	ERK Inhibitor (pan) 21	LY3214996 inhibits ERK1/2, potentially resulting in decreased growth of tumors with alterations in the RAS/MAPK pathway (AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4973, PMID: 31744895).

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Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
BRAF L597Q FGFR2 H167_N173del FGFR2 L618F	intrahepatic cholangiocarcinoma	no benefit	LY3214996	Case Reports/Case Series	Actionable	In a clinical case study, LY3214996 treatment led to progressive disease after 2 months in an intrahepatic cholangiocarcinoma patient harboring BRAF L597Q, FGFR2 H167_N173del, and FGFR2 L618F (PMID: 33926920).	33926920
BRAF L597Q FGFR2 H167_N173del FGFR2 N550K FGFR2 L618F NRAS Q61K	intrahepatic cholangiocarcinoma	predicted - resistant	LY3214996	Case Reports/Case Series	Actionable	In a clinical case study, acquired NRAS Q61K and FGFR2 N550K mutations were identified following progression on LY3214996 in an intrahepatic cholangiocarcinoma patient harboring BRAF L597Q, FGFR2 H167_N173del, and FGFR2 L618F (PMID: 33926920).	33926920
NRAS Q61K	lung carcinoma	sensitive	LY3214996	Preclinical - Pdx & cell culture	Actionable	In a preclinical study, patient-derived lung carcinoma cells harboring NRAS Q61K were sensitive to LY3214996 treatment in culture, and LY3214996 treatment led to reduction of tumor growth in a patient-derived xenograft (PDX) model (PMID: 33536188).	33536188
BRAF V600E	melanoma	sensitive	LY3214996	Preclinical - Cell line xenograft	Actionable	In a preclinical study, LY3214996 treatment in a melanoma cell line harboring BRAF V600E led to decreased cell proliferation in culture, and inhibition of tumor growth in a cell line xenograft model (PMID: 31744895).	31744895
MAP2K1 Q56P MAP2K1 H119Y MAP2K1 D351G	colorectal cancer	predicted - sensitive	LY3214996	Preclinical - Cell line xenograft	Actionable	In a preclinical study, LY3214996 treatment in a colorectal cancer cell line harboring MAP2K1 Q56P, MAP2K1 H119Y, and MAP2K1 D351G led to decreased cell proliferation in culture, and inhibition of tumor growth in a cell line xenograft model (PMID: 31744895).	31744895
BRAF G469A	lung adenocarcinoma	resistant	LY3214996	Preclinical - Patient cell culture	Actionable	In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF G469A were resistant to treatment with LY3214996 in culture (PMID: 32540409).	32540409
BRAF L597V	lung adenocarcinoma	resistant	LY3214996	Preclinical - Patient cell culture	Actionable	In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were resistant to treatment with LY3214996 in culture (PMID: 32540409).	32540409
BRAF T119S BRAF V600E	colorectal cancer	predicted - sensitive	LY3214996	Preclinical - Cell culture	Actionable	In a preclinical study, a colorectal cancer cell line harboring BRAF V600E and BRAF T119S was sensitive to treatment with LY3214996 in culture, demonstrating decreased cell proliferation (PMID: 31744895).	31744895
BRAF V600E	colorectal cancer	predicted - sensitive	LY3214996	Preclinical - Cell culture	Actionable	In a preclinical study, a lung cancer cell line harboring BRAF V600E and NF1 T2805I was sensitive to treatment with LY3214996 in culture, demonstrating decreased cell viability (PMID: 31744895).	31744895
MAP2K1 Q56P	lung cancer	predicted - sensitive	LY3214996	Preclinical - Cell culture	Actionable	In a preclinical study, a lung cancer cell line harboring MAP2K1 Q56P was sensitive to treatment with LY3214996 in culture, demonstrating decreased cell proliferation (PMID: 31744895).	31744895
NRAS Q61L	melanoma	predicted - sensitive	LY3214996	Preclinical - Cell culture	Actionable	In a preclinical study, a melanoma cell line harboring NRAS Q61L was sensitive to treatment with LY3214996 in culture, demonstrating decreased cell proliferation (PMID: 31744895).	31744895

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Clinical Trial	Phase	Therapies	Title	Recruitment Status	Covered Countries	Other Countries
NCT02857270	Phase I	LY3214996 Gemcitabine + LY3214996 + Nab-paclitaxel LY3214996 + Midazolam Abemaciclib + LY3214996	A Study of LY3214996 Administered Alone or in Combination With Other Agents in Participants With Advanced/Metastatic Cancer	Completed	USA \| FRA \| AUS	1
NCT04081259	Phase I	LY3214996	LY3214996 in Patients With AML Who Are Not Candidates for Standard Therapy	Completed	USA	0
NCT04386057	Phase II	Hydroxychloroquine + LY3214996 LY3214996	LY3214996 +/- HCQ in Pancreatic Cancer	Completed	USA	0

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