Anti-CSF1R Monoclonal Antibody IMC-CS4, Vemurafenib, and Cobimetinib in Treating Patients with Melanoma That is Metastatic or Cannot Be Removed by Surgery

Inclusion Criteria

• For enrollment to the phase I portion: participants must have a histologically confirmed melanoma with a BRAF V600E or BRAF V600K mutation (identified via next generation [NextGen] sequencing using the Dana-Farber Cancer Institute [DFCI]/Brigham and Women's Hospital [BWH] OncoPanel or any Clinical Laboratory Improvement Act [CLIA]-certified method) that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective
• For enrollment to the phase II portion: participants must have a histologically confirmed melanoma with a BRAF V600E or BRAF V600K mutation (identified via NextGen sequencing using the DFCI/BWH OncoPanel or any CLIA-certified method) and cannot have received prior BRAF or MEK inhibitor therapy
• Participants enrolling to the phase I portion of the trial must have evaluable or measurable disease
• Participants enrolling to the phase II portion of the trial 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 >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1
• Absolute neutrophil count >= 1.5 K/uL
• Platelets >= 100 K/uL
• Hemoglobin >= 9 g/dL
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN
• Serum creatinine =< 1.5 x institutional ULN
• Prothrombin time (PT)-international normalized ratio (INR) =< 1.5 x institutional ULN (for participants on anticoagulation therapy, =< 1.5 x their baseline value)
• Activated partial thromboplastin time (aPTT) =< 1.5 x institutional ULN (for participants on anticoagulation therapy, =< 1.5 x their baseline value)
• Participants must have a left ventricular ejection fraction (LVEF) >= 50%
• Participants must have a corrected QT (QTc) of =< 470 msec on the screening electrocardiography (EKG)
• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; 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 LY3022855 administration
• Ability to understand and the willingness to sign a written informed consent document
• Participants must have archival tumor tissue available; participants without archival tissue may be enrolled at the discretion of the principal investigator

Exclusion Criteria

• Participants who have had chemotherapy, radiotherapy, biologic therapy, major surgery, or another investigational agent within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
• For enrollment to the phase I portion: there is no required washout period for BRAF or MEK inhibitor therapy
• Participants who have not recovered to =< Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or baseline from toxicity as a result of previous cancer treatment prior to entering the study (with the exception of alopecia and peripheral neuropathy which can be =< grade 2)
• For enrollment to the phase II portion: participants who have received prior BRAF or MEK inhibitor therapy
• Participants with known untreated brain metastases should be excluded from this clinical trial; participants with a history of brain metastases that have been treated, are no longer taking corticosteroids, and have been stable on imaging for >= 4 weeks following the last date of treatment are permitted
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to LY3022855, vemurafenib, or cobimetinib
• 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; breastfeeding should be discontinued if the mother is treated with LY3022855; these potential risks may also apply to the other agents used in this study
• Participants with a known history of human immunodeficiency virus (HIV) are ineligible; appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated
• Participants with a personal or family history of long QT syndrome
• Participants with a history of a second primary malignancy; exceptions include: patients with a history of malignancies that were treated curatively and have not recurred within 3 years prior to study entry; resected basal and squamous cell carcinomas of the skin, and completely resected carcinoma in situ of any type
• Participants with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of vemurafenib and cobimetinib in the opinion of the treating investigator (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
• Participants who are unable to swallow or retain oral medication
• Participants that require co-administration of strong or moderate CYP3A inhibitors, as these medications may alter vemurafenib and cobimetinib concentrations
• Participants who require treatment with medications that are strong or moderate CYP3A inducers, as these medications may alter the concentration of cobimetinib
• Participants with evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration