Ibrutinib in Treating Patients With Refractory Metastatic Cutaneous Melanoma

PRIMARY OBJECTIVES: I. Estimate rate of objective response (OR: complete response \[CR\] + partial response \[PR\]) to ibrutinib administered as single agent in patients with immune checkpoint inhibitor-refractory, or immune checkpoint inhibitor ineligible and mitogen-activated protein kinase (MAPK) inhibitor-refractory (if B-Raf proto-oncogene, serine/threonine kinase \[BRAF\]V600-mutant) or MAPK inhibitor-intolerant distant metastatic cutaneous melanoma. SECONDARY OBJECTIVES: I. Estimate progression-free survival (PFS) rate at 6 months after initiation of ibrutinib in patients with immune checkpoint inhibitor-refractory or immune checkpoint ineligible and MAPK inhibitor-refractory (if BRAFV600-mutant) or MAPK inhibitor-intolerant distant metastatic cutaneous melanoma. II. Estimate overall survival (OS) after initiation of ibrutinib in patients with immune checkpoint inhibitor-refractory or immune checkpoint ineligible and MAPK inhibitor-refractory (if BRAFV600-mutant) or MAPK inhibitor-intolerant distant metastatic cutaneous melanoma. III. Explore the association of ITK protein expression with OR and PFS. TERTIARY OBJECTIVES: I. Explore association between other putative targets of ibrutinib (e.g. Tec, ErbB4, Hck, Yes, BTK) in melanoma cells, as assessed by 2-color immunofluorescence (IF) in representative tissue sections obtained from pretreatment archived formalin-fixed paraffin-embedded (FFPE) tumor blocks or FFPE blocks obtained from fresh tissue biopsy from enrolled patients, with overall response (OR) and PFS. II. Explore ibrutinib-mediated effect(s) on immune cell subsets associated with immunomodulation by performing multiparameter flow cytometric analysis in peripheral blood mononuclear cell (PBMC) obtained prior to treatment, on day 29 (i.e., predose day 1 of cycle 2) following initiation of treatment with ibrutinib, and at the time of disease progression (3 time points). III. Determine pharmacokinetics (PK) of ibrutinib following daily dosing at 840 mg on day 8 of cycle 1 (Css). OUTLINE: Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for up to 2 years.