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Therapy Name	Ravoxertinib
Synonyms
Therapy Description	Ravoxertinib (GDC-0994) is a small molecule inhibitor of ERK1 and ERK2, which may decrease tumor growth (Cancer Res October 1, 2014 74:DDT02-03, PMID: 32311798, PMID: 31848189).

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Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
Ravoxertinib		GDC-0994	ERK Inhibitor (pan) 21	Ravoxertinib (GDC-0994) is a small molecule inhibitor of ERK1 and ERK2, which may decrease tumor growth (Cancer Res October 1, 2014 74:DDT02-03, PMID: 32311798, PMID: 31848189).

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Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
BRAF V600E	colorectal cancer	predicted - sensitive	Ravoxertinib	Case Reports/Case Series	Actionable	In a Phase I trial, two colorectal cancer patients harboring BRAF V600E achieved partial responses lasting 21 and 73 weeks following treatment with Ravoxertinib (GDC-0994) (PMID: 31848189; NCT01875705).	31848189
BRAF V600E	anaplastic thyroid carcinoma	sensitive	Ravoxertinib	Preclinical - Cell line xenograft	Actionable	In a preclinical study, Ravoxertinib (GDC-0994) inhibited viability and colony formation and induced cell cycle arrest in an anaplastic thyroid carcinoma cell line harboring BRAF V600E in culture, and inhibited tumor growth in a cell line xenograft model (PMID: 38728872).	38728872
BRAF G469A	lung adenocarcinoma	resistant	Ravoxertinib	Preclinical - Patient cell culture	Actionable	In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF G469A were resistant to treatment with Ravoxertinib (GDC-0994) in culture (PMID: 32540409).	32540409
BRAF L597V	lung adenocarcinoma	resistant	Ravoxertinib	Preclinical - Patient cell culture	Actionable	In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were resistant to treatment with Ravoxertinib (GDC-0994) in culture (PMID: 32540409).	32540409
BRAF V600E	papillary thyroid carcinoma	sensitive	Ravoxertinib	Preclinical - Cell culture	Actionable	In a preclinical study, Ravoxertinib (GDC-0994) inhibited viability and colony formation in papillary thyroid carcinoma cell lines harboring BRAF V600E in culture (PMID: 38728872).	38728872
BRAF V600E	melanoma	sensitive	Ravoxertinib	Preclinical - Cell culture	Actionable	In a preclinical study, Ravoxertinib (GDC-0994) inhibited viability and colony formation in melanoma cell lines harboring BRAF V600E in culture (PMID: 38728872).	38728872
BRAF V600E MAP2K1 D67N	melanoma	decreased response	Ravoxertinib	Preclinical - Cell culture	Actionable	In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 D67N was less responsive to Ravoxertinib (GDC-0994) compared to cells expressing wild-type MAP2K1 in culture (PMID: 36442478).	36442478
BRAF V600E MAP2K1 E203K	melanoma	decreased response	Ravoxertinib	Preclinical - Cell culture	Actionable	In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 E203K was less responsive to Ravoxertinib (GDC-0994) compared to cells expressing wild-type MAP2K1 in culture (PMID: 36442478).	36442478
BRAF V600E MAP2K1 I99_K104del	melanoma	decreased response	Ravoxertinib	Preclinical - Cell culture	Actionable	In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 I99_K104del was less responsive to Ravoxertinib (GDC-0994) compared to cells expressing wild-type MAP2K1 in culture (PMID: 36442478).	36442478
BRAF V600E MAP2K1 P124S	melanoma	decreased response	Ravoxertinib	Preclinical - Cell culture	Actionable	In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P124S was less responsive to Ravoxertinib (GDC-0994) compared to cells expressing wild-type MAP2K1 in culture (PMID: 36442478).	36442478
NRAS Q61K	anaplastic thyroid carcinoma	sensitive	Ravoxertinib	Preclinical - Cell culture	Actionable	In a preclinical study, Ravoxertinib (GDC-0994) inhibited viability of an anaplastic thyroid carcinoma cell line harboring NRAS Q61K in culture (PMID: 38728872).	38728872

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Clinical Trial	Phase	Therapies	Title	Recruitment Status	Covered Countries	Other Countries
NCT01875705	Phase I	Ravoxertinib	A Dose-Escalation Study of GDC-0994 in Patients With Locally Advanced or Metastatic Solid Tumors	Completed	USA \| FRA	0
NCT02457793	Phase I	Cobimetinib Ravoxertinib	A Study of the Safety, Tolerability, and Effects of Cobimetinib and GDC-0994 in Patients With Locally Advanced or Metastatic Solid Tumors	Completed	USA	0

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