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Ref Type | Journal Article | ||||||||||||
PMID | (35551160) | ||||||||||||
Authors | Wolfe Z, Friedland JC, Ginn S, Blackham A, Demberger L, Horton M, McIntosh A, Sheikh H, Box J, Knoerzer D, Federowicz B, Stuhlmiller TJ, Shapiro M, Nair S | ||||||||||||
Title | Case report: response to the ERK1/2 inhibitor ulixertinib in BRAF D594G cutaneous melanoma. | ||||||||||||
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Abstract Text | Melanoma is characterized by oncogenic mutations in pathways regulating cell growth, proliferation, and metabolism. Greater than 80% of primary melanoma cases harbor aberrant activation of the mitogen-activated protein kinase kinase/extracellular-signal-regulated kinase (MEK/ERK) pathway, with oncogenic mutations in BRAF, most notably BRAF V600E, being the most common. Significant progress has been made in BRAF-mutant melanoma using BRAF and MEK inhibitors; however, non-V600 BRAF mutations remain a challenge with limited treatment options. We report the case of an individual diagnosed with stage III BRAF D594G-mutant melanoma who experienced an extraordinary response to the ERK1/2 inhibitor ulixertinib as fourth-line therapy. Ulixertinib was obtained via an intermediate expanded access protocol with unique flexibility to permit both single-agent and combination treatments, dose adjustments, breaks in treatment to undergo surgery, and long-term preventive treatment following surgical resection offering this patient the potential for curative treatment. |
Molecular Profile | Treatment Approach |
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Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
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Gene | Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
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Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
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BRAF D594G | melanoma | predicted - sensitive | Ulixertinib | Case Reports/Case Series | Actionable | In a clinical case study, Ulixertinib (BVD-523) treatment resulted in a histologic response allowing for surgical resection in a patient with metastatic melanoma harboring BRAF D594G (PMID: 35551160; NCT04566393). | 35551160 |