Ulixertinib in Treating Patients with Stage IV Uveal Melanoma

Inclusion Criteria

• Participants must have histologically or cytologically confirmed stage IV uveal melanoma
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
• Patients can have received any number of prior therapies for treatment of their uveal melanoma excluding prior treatment with an ERK inhibitor; patients who have received prior MEK inhibition or other MAPK targeted agents will be allowed on study
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Life expectancy of greater than 6 months
• Leukocytes >= 3,000/mcL
• Hemoglobin >= 9.0 g/dL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Total bilirubin =< 1.5 x institutional upper limit of normal
• Alanine aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/aspartate aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal, unless there is known liver involvement in which case =< 5.0 x institutional upper limit of normal
• Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal
• Participants must have adequate cardiac function, e.g. left ventricular ejection fraction (LVEF) of > 50% as assessed by multi-gated acquisition (MUGA) or ultrasound/echocardiography (ECHO); corrected QT interval (QTc) < 470ms
• Presence of metastatic disease that would be amenable to the required biopsies; ideally pre and post biopsies should be from the same lesion and otherwise from lesions in the same organ; if not possible, then biopsy of the lesions in different organs will be permitted. Archival tissue from a biopsy taken within 6 months prior to the first study treatment may be used in place of a pre-treatment biopsy at the discretion of the principal investigator
• The effects of BVD-523 on the developing human fetus are unknown; for this reason and because ERK inhibitors could potentially be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 4 months after completion of BVD-523 administration; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of BVD-523 administration
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C), small molecule targeted therapy (i.e. – kinase inhibitors) within 3 weeks or the last dose of antibody therapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Participants who are receiving any other investigational agents
• Major surgery within 4 weeks of the first dose of BVD-523; tumor embolization procedure or ablation procedure within 2 weeks of first dose of BVD-523
• Participants with known brain metastases or evidence of leptomeningeal involvement are eligible only if these lesions are treated and both clinically and radiographically stable for at least four weeks; patients are eligible if they are being treated with a stable dosage of steroids/anticonvulsants, requiring no dose increase for 4 weeks
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to BVD-523
• Participants receiving any medications or substances that are known to be strong inhibitors of CYP1A2, CYP2D6, and CYP3A4 or strong inducers of CYP3A4 are ineligible
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because BVD-523 is an ERK with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with BVD-523 breastfeeding should be discontinued if the mother is treated with BVD-523
• Gastrointestinal (GI) condition which could impair absorption of study medication or inability to ingest study medication
• A history of current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)
• Concomitant malignancies or previous malignancies with less than 2 years of disease-free interval at the time of enrollment (except non-melanoma skin cancer, cervical cancer in situ, prostate cancer with undetectable prostate specific antigen [PSA]); other concurrent malignancies must be discussed with the medical monitor prior to enrollment
• Patients with melanoma of cutaneous, mucosal or acral-lentiginous origin or of unknown primary