Patients must have BRAF V600E or BRAF V600K mutation identified by a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory; acceptable analytic techniques include but are not restricted to deoxyribonucleic acid (DNA) sequencing, pyrosequencing, polymerase chain reaction (PCR), melting point assays, and immunohistochemistry
Patients must have BRAF V600 mutation, identified by a Food and Drug Administration (FDA)-approved test at a Clinical Laboratory Improvement Act (CLIA)-certified lab; if test at CLIA-certified lab used a non-FDA approved method, information about the assay must be provided (FDA approved tests for BRAF V600 mutations in melanoma include: THxID BRAF Detection Kit and Cobas 4800 BRAF V600 Mutation Test)
Histologically proven papillary craniopharyngioma as documented by central pathology review with positive BRAF V600E mutation by IHC
Group 2: Melanoma: All patients must have been tested for BRAF mutations. Patients with V600 mutation positive melanoma must have clinical or radiological evidence of disease progression during or after treatment with a BRAF inhibitor alone or in combination with other agents.
Patients must have histologically confirmed diagnosis of stage IV metastatic melanoma positive for BRAF V600E by a Clinical Laboratory Improvement Amendments (CLIA) approved assay
If BRAF mutation status is unknown, before randomization the subject must have BRAF testing performed using an approved assay method.
No known activating mutations in KRAS, NRAS, HRAS and BRAF
Patients with melanoma should have unresectable or metastatic disease; melanoma patients with BRAF V600E or V600K mutation-positive melanoma who have previously received a BRAF inhibitor with or without a MEK inhibitor) are eligible
Tumors harboring known activating KRAS, NRAS, HRAS, BRAF or PTPN11 (SHP2) mutations.
Malignancy of non-squamous histology that carries a BRAF, KRAS, NRAS or HRAS mutation(s).
BRAF mutation in loci other than V600 (BRAF nonV600 MUT) or BRAF fusion detected by genetic testing of the primary tumor or regional/distant metastasis
BRAF mutation-positive (V600 E or K) melanoma for Parts 1, 2 and 3, or for Parts 1, 2, 4 and 5 only BRAF mutation-negative (wild type) melanoma with documented progression of >=1 measurable lesion after prior therapy (if prior therapy was received). The inclusion criterion does not apply to participants with solid tumors in Parts 4 and 5 (dose confirmation only).
Prior systemic therapy (for participants who are BRAF mutation-positive), or BRAF mutation-negative and has received >1 prior systemic therapy for metastatic melanoma
BRAF mutation-positive and has received prior systemic therapy with ipilimumab or other anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) blocking antibodies. The BRAF exclusion criterion does not apply to participants with solid tumor in Parts 4 and 5 (dose confirmation only).
Patients must have histologically confirmed, BRAF-mutant (V600E/K) melanoma (molecularly confirmed using validated, commercially available assay performed in a Clinical Laboratory Improvement Act [CLIA]-approved laboratory) that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective\r\n* If test at CLIA-certified lab used a non-Food and Drug Administration (FDA) approved method, information about the assay must be provided; (FDA approved tests for BRAF V600 mutations in melanoma include: THxID BRAF Detection Kit and Cobas 4800 BRAF V600 Mutation Test)
BRAF V600 mutation-positive malignancy
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 have had progression of disease on prior BRAF and MEK inhibitor therapy
Has testing for a BRAF mutation prior to study entry
Have documentation of V600-activating BRAF mutation status or consent to BRAF V600 mutation testing during the screening period.
Patients whose melanomas harbor a BRAF V600E or V600K mutation must have progressed on a RAF inhibitor; patients who had to discontinue RAF inhibitor therapy because of toxicity but who did not progress will be eligible unless they responded to therapy; in that case, they will not be eligible unless they progress
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
Negative result of BRAFV600E and BRAF Ins T screening test
Only patients with v-raf murine sarcoma viral oncogene homolog B (BRAF) V600E or V600K mutated tumors will be enrolled
Patients whose BRAF V600E mutation status is unknown, have the BRAF V600E mutation and are responding to a BRAF inhibitor or MEK inhibitor therapy, or have the BRAF V600E mutation and have not been offered the option of receiving a BRAF inhibitor or MEK inhibitor therapy for the treatment of their melanoma
Participant is willing to sign a screening consent and provide pre-trial tumor material for BRAF testing (both for BRAF V^600E mutation and BRAF KIAA1549 fusion assessments)\r\n* All patients who are candidates for enrollment in stratum 5 based on their tumor histology must be pre-screened\r\n* Screening may be applied to potential stratum 1 and 2 patients
Patients whose prior BRAF testing was performed at another lab (Clinical Laboratory Improvement Amendments [CLIA]/College of American Pathologist [CAP] certified or otherwise) must send additional tumor material to Brigham and Women's Hospital (BWH) for confirmation; however, to preserve available tumor material, patients whose tumor material has previously undergone BRAF analysis at the Lindeman and Ligon Labs at Brigham and Women’s Hospital using the same procedures as described in this protocol, will not be required to submit additional tumor material for analysis; these patients must have both the BRAFV600E mutation and BRAF KIAA1549 fusion assessments done and if only one test was previously conducted; additional tissue will be required for the second test
For Dose-Escalation Phase: Patients must have histologically confirmed, BRAF-mutant (V600E/K) malignancy molecularly confirmed using Cobas assay or a comparable Food and Drug Administration (FDA)-approved assay (for exceptions, see below*) that is metastatic or unresectable, have received and tolerated prior BRAF or BRAF and MEK inhibitor (BRAF targeted) therapy or not previously received BRAF targeted therapy, and for which standard curative or palliative measures do not exist or are no longer effective.\r\n* If test at Clinical Laboratory Improvement Act (CLIA)-certified lab used a non-FDA approved method, information about the assay must be provided to the overall principal investigator (PI) for approval. (FDA approved tests for BRAF V600 mutations in melanoma include: THxID BRAF detection kit and Cobas 4800 BRAF V600 mutation test).
For Dose-Expansion Phase: Patients must have histologically confirmed, BRAF-mutant (V600E/K) melanoma (molecularly confirmed using Cobas assay or a comparable FDA-approved assay (for exceptions, see below*) that is metastatic or unresectable, have received and tolerated prior BRAF or BRAF and MEK inhibitor (BRAF targeted) therapy at full dose or not previously received BRAF targeted therapy.\r\n* If test at CLIA-certified lab used a non-FDA approved method, information about the assay must be provided to the overall principal investigator (PI) for approval. (FDA approved tests for BRAF V600 mutations in melanoma include: THxID BRAF detection kit and Cobas 4800 BRAF V600 mutation test).
Participants must have BRAFV600-mutation status known (molecularly confirmed using validated, commercially available assay performed in a Clinical Laboratory Improvement Act [CLIA] approved laboratory)\r\n* If test at CLIA-certified lab used a non-Food and Drug Administration (FDA) approved method, information about the assay must be provided; (FDA approved tests for BRAF V600 mutations in melanoma include: THxID BRAF Detection Kit and Cobas 4800 BRAF V600 Mutation Test)
Harboring a mutation in the BRAF oncogene or the KRAS or the NRAS oncogene
Presence of KRAS or BRAF mutation in tumor tissue
Histologically confirmed metastatic melanoma (stage IV) or unresectable stage III; patients with BRAF or BRAF-wild-type are eligible; only BRAF V600 mutated melanoma will be eligible for the triplet arm while BRAF-wild-type or NRAS-mutated melanoma will be eligible for the doublet arm
Known or ordered molecular testing for MSI, BRAF, and KRAS status
One of the following:\r\n* Documentation of BRAF V600E mutation and inability to access BRAF inhibitor or prior treatment with a BRAF inhibitor discontinued due to intolerable side effects or toxicity prior to progression OR\r\n* Documentation of wild-type BRAF V600 mutational status
Participants with age greater than or equal to (>=) 18 years with either unresectable Stage IIIC or Stage IV metastatic melanoma positive for the BRAF V600 mutation, or other malignant tumor types that harbor a V600-activating mutation of BRAF
CAPMATINIB INCLUSION CRITERIA: Documentation of absence of activating and targetable BRAF or NRAS point mutations
REGORAFENIB INCLUSION CRITERIA: Documentation of absence of activating and targetable BRAF or NRAS point mutations
ENTRECTINIB INCLUSION CRITERIA: Documentation of absence of activating and targetable BRAF or NRAS point mutations
Patients must have a histologically or cytologically confirmed solid malignancy that is metastatic or unresectable for which standard curative or palliative treatments do not exist or are no longer effective\r\n* Hepatocellular carcinoma (HCC) patients are not required to have histologically or cytologically confirmed malignancy, patients are considered eligible based on tumor markers and/or imaging assessment\r\n* Patients with the following tumor types will be excluded from the normal and mild cohorts:\r\n** Pancreatic cancer patients\r\n** Colorectal cancer patients \r\n** BRAF V600E melanoma patients who have failed BRAF inhibitors\r\n*** Note: Patients with pancreatic cancer, colorectal cancer, and BRAF V600E melanoma patients who have failed BRAF inhibitors are allowed to enroll in the moderate and severe cohorts provided the patients: 1) sign a separate consent form which outlines the extremely limited activity observed in prior studies, and 2) are consented to the study by a protocol-specified designee who is not their longitudinal oncologist
Histologically and/or cytologically confirmed, non-small cell lung cancer (NSCLC) of adenocarcinoma histology at the time of initial diagnosis.\r\na) Mixed tumors will be categorized by the predominant cell type; (Note: If small cell elements are present the patient is ineligible)\r\nb) Known mutational status of KRAS and BRAF oncogenes.\r\nc) For patients in whom mutational testing result is unknown or unavailable from a prior test, KRAS and BRAF testing will be performed (at a CLIA-certified laboratory) using an archived or fresh biopsy as per Standard of Care, prior to enrollment.
B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E or other known dabrafenib sensitive BRAF mutation in tumor by any Clinical Laboratory Improvement Amendments (CLIA) certified lab; may include, for example, Sanger sequencing, SNaPshot platform, immunohistochemistry, Foundation One tests, etc.)
COHORT B: Confirmation in a CLIA certified laboratory that one of the patient’s thyroid tumors (primary tumor, recurrent tumor, or metastasis) does not have any of the following mutations:\r\n* Mutation at V600 of the v-raf murine sarcoma viral oncogene homolog B (BRAF) gene\r\n* Mutation in NRAS or KRAS or HRAS at G12, G13, or Q61\r\n* These patients will be designated “BRAF/RAS wild type (WT)”
Patients must have histologically confirmed, BRAF-mutant (V600E/K) solid tumor (molecularly confirmed using Cobas assay or a comparable Food and Drug Administration [FDA]-approved assay) that is metastatic or unresectable, have received and tolerated prior BRAF or BRAF and MEK inhibitor (BRAF targeted) therapy at full dose or not previously received BRAF targeted therapy, and for which standard curative measures do not exist or are no longer effective\r\n* If test at Clinical Laboratory Improvement Act (CLIA)-certified laboratory (lab) used a non-FDA approved method, information about the assay must be provided; (FDA approved tests for BRAF V600 mutations in melanoma include: THxID BRAF Detection Kit and Cobas 4800 BRAF V600 Mutation Test)
Any patient with metastatic melanoma from any site whose tumor is BRAF V600E mutation (V600EBRAF) positive, regardless of prior treatment will be eligible; these include untreated patients or those treated with chemotherapy, biochemotherapy or a prior BRAF-inhibitor
Patients must have undergone/undergo testing for v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600 mutation status
Stage IV patients must have refused, be ineligible for, or have failed at least one non-vaccine based systemic therapy (such as, high dose IL-2, dacarbazine/temozolomide, ipilimumab, or participation in a clinical trial); patients who are BRAF V600E mutation positive need to have failed, refused, or be ineligible for at least 2 lines of therapy (vemurafenib plus one other regimen)
Group 1: BRAF mutant melanoma (Part B)
Patients whose tumors harbor the BRAF V600E mutation, must have demonstrated progression on or intolerance to the combination of dabrafenib and trametinib
Sufficient tumor available to determine if expresses wild-type or mutated BRAF if result not already known; the presence or absence of BRAF mutation needs to be determined at Brigham and Women's Cancer Center (BWH), or by Drs. Christopher Corless and Michael Heinrich at Cancer Pathology Shared Resource Oregon Health & Science University, or in context of eligibility assessment after signing consent to a previous clinical trial
Agreement to allow tumor to be evaluated for mutations in KIT and BRAF
BRAF- or MEK-mutation melanoma tumor status will be established prior to entry based on previous BRAF-gene analysis or MEK pathway mutation reports from a CLIA qualified laboratory. If a report is not available, the mutation analysis will be performed at Screening on archival tissue
Documented wild-type in KRAS and NRAS (codons 12, 13, 59, 61, 117, and 146) and in BRAF codon 600, based on tumor tissue taken from primary or metastatic site and tested for biomarkers
Confirmed wild-type status in KRAS exons 2, 3, and 4; NRAS exons 2, 3, and 4; and BRAF, by standard of care testing of tumor specimen; tissue used for testing may have been collected prior to treatment with cetuximab
Patient must have been already tested and have available results of the mutations status of KRAS/NRAS/BRAF and EGFR from the circulating tumor DNA within 10 weeks prior to starting study therapy
In cohort 3, must not have EGFR ectodomain mutation or any mutations in KRAS, NRAS, or BRAF
Unresectable or metastatic melanoma with known v-raf murine sarcoma viral oncogene homolog B (BRAF) mutation status
Patients must have known v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutational status of tumor; wild-type (WT) or mutated, prior to randomization
TREATMENT: Patients with melanoma and known v-raf murine sarcoma viral oncogene homolog B (BRAF) V600E mutations must have received and progressed on specific BRAF inhibitor therapy
Patients must have BRAFV600E or BRAFV600K mutations, identified by a Food and Drug Administration (FDA)-approved test at a Clinical Laboratory Improvement Amendments (CLIA)-certified lab; if test at CLIA-certified lab used a non-FDA approved method, information about the assay must be provided; (FDA approved tests for BRAF V600 mutations in melanoma include: THxID BRAF Detection Kit and Cobas 4800 BRAF V600 Mutation Test)
Patients with wild type BRAF gene molecular results on ECD affected tissue
Patients must have measurable and histologically or cytologically confirmed thyroid cancer with a BRAF V600E or V600K (c. 1799 T to A and c.1799_1800TG>AA) mutation that is not considered curable by surgery; confirmation will be done at Memorial Sloan Kettering (MSK); only tumors with a BRAFV600E or BRAFV600K mutation will be eligible for the clinical study; BRAF status will be assessed in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory; BRAF status may also be tested with any Food and Drug Administration (FDA)-approved test (such as Cobas 4800 BRAF V600 Mutation Test)
Tumor may have a v-raf murine sarcoma viral oncogene homolog B (B-RAF) V600 mutation or be BRAF wild type, and patients must not have been previously treated with ipilimumab
Patients may have been previously treated for metastatic disease, or may have not had prior systemic treatment; patients with a V600 BRAF mutated tumor may have previously received a prior BRAF inhibitor
Tumor must have a v-raf murine sarcoma viral oncogene homolog B (B-RAF) V600E, D or K mutation by Cobas pyrosequencing assay or equivalent
Documentation of V600E-activating BRAF mutation status.
Melanoma\r\n* Unresectable or metastatic disease progression following a B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitor if BRAF V600 positive\r\n* Note: prior therapy with ipilimumab not required
Patients BRAF mutation status must be known
Inability to assess BRAF or NRAS mutation status; hypersensitivity to digoxin
Patients must have their tumor sent for v-Raf murine sarcoma viral oncogene homolog B1(BRAF) mutational analysis
Either treatment naïve or received only one line of systemic anticancer therapy if v-raf murine sarcoma viral oncogene homolog B1 (BRAF) wild-type or up to two lines of systemic anticancer therapy including one BRAF inhibitor-containing regimen if BRAF mutant. Treatments given in an adjuvant setting (eg, interferon, radiotherapy, isolated limb perfusion, or investigational agents) are not considered as prior lines of therapy. No prior talimogene laherparepvec, other oncolytic virus therapies, or tumor vaccines are allowed, even if given in the adjuvant setting.
BRAF V600 mutation status of the current primary tumor or involved lymph node determined to be positive using the cobas BRAF V600 mutation test
Those with BRAF wild type may have had a maximum of two previous systemic regimens for the treatment of melanoma.
Those with a BRAF mutation may have had a maximum of three previous systemic regimens for the treatment of melanoma.
For patients with metastatic melanoma not of uveal origin, v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600 mutation determination using a Clinical Laboratory Improvement Amendments (CLIA)-approved testing method on metastatic tumor tissue\r\n* NOTE: patients with metastatic melanoma of uveal origin do not need to have formal BRAF testing due to low probability of a BRAF V600 mutation in their metastatic tumor
Patients must have received a biologic therapy (interleukin 2 or ipilimumab) and a BRAF and/or MEK inhibitor (if tumor contains the V600E or V600K mutation) for metastatic disease; if patient did not receive such agents, rationale for not treating the patients with the agent must be cleared study principal investigator (PI) (ie no V600e/k BRAF mutation or patient with autoimmunity, thus not eligible for biologic therapy)
Evaluation of v-raf murine sarcoma viral oncogene homolog B (BRAF)V600 mutation status
The tumor tissue must have been determined to be KRAS, NRAS, BRAF, PIK3CA wild-type by central CLIA testing.
Must have a a BRAF V600E mutation-positive tumor as confirmed by an approved local laboratory or a sponsor designated central reference laboratory. All subjects must provide an archived or fresh tumor sample (for solid tumors) or a fresh BM aspirate and peripheral blood sample (for HCL and MM) for confirmation testing of the BRAF V600E mutation by a sponsor designated central reference laboratory using a sponsor designated assay
Presence of BRAF V600E or V600K mutation in tumor tissue prior to randomization
Willing to provide tissue as required per protocol for central BRAF^V600X mutation testing\r\n* NOTE: patients with prior BRAF^600X testing that demonstrate a mutation at V600X will be allowed to enroll prior to central testing if the assay was performed at a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory assay; this includes THxID, BRAF Detection Kit, Cobas 4800 BRAF600 mutation test and other CLIA-certified assays available at participating institutions
Patients with unknown BRAF^600X status: histologically confirmed melanoma, papillary thyroid, cholangiocarcinoma or testicular cancer that is metastatic or unresectable and for which the investigator feels a BRAF^600X targeted agent is a reasonable treatment\r\n* NOTE: patient must be screened by central BRAF testing and must demonstrate a V600 mutation prior to start of study agent\r\n* Note: other tumor types without known BRAF^600X mutations will not be eligible for central testing
Patients with known BRAF^V600X mutation: patients must have BRAF^V600X mutated, histologically confirmed cancer that is metastatic or unresectable and for which curative or standard therapies do not exist or are no longer effective\r\n* NOTE: colorectal cancers with BRAF mutations ARE NOT allowed\r\n* NOTE: any mutation at the V600 position that results in a change from V (valine) is allowed; this includes E, D, K, R or other mutations not noted here at the V600 position
Patients must have BRAF^V600 mutant metastatic cancer irrespective of the histology or prior therapy; BRAF^V600 mutant status must be documented by a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory; use of an Food and Drug Administration (FDA)-approved test is preferred although other BRAF tests at a CLIA-certified laboratory may also be accepted
Patients must have histologically confirmed diagnosis of stage IV metastatic melanoma positive for BRAF V600E mutation by either the COBAS test or other Clinical Laboratory Improvement Amendments (CLIA) approved assay
Histologically confirmed V600E or V600K BRAF mutant melanoma
Presence of BRAF mutation or genes fusion involving BRAF in tumor tissue
Unknown BRAF status
A documented BRAF V600E or BRAF V600K mutation by genotyping or immunohistochemistry (IHC) performed by a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory
Confirmation of BRAF mutation-positive malignancy is required for selection of patients for vemurafenib therapy
Melanoma with BRAF V600E or V600K mutation-positive melanoma must have progressed on, or were intolerant to, prior BRAF- or MEK-inhibitor therapy
Positive proto-oncogene B-Raf (BRAF) mutation result (Cobas 4800 BRAF V600 Mutation Test)
Confirmation in a CLIA certified laboratory or in an FDA-approved assay that one of the patient's thyroid tumors (primary tumor, recurrent tumor, or metastasis) possesses a BRAF mutation at V600.
Patients with metastatic or locally advanced and unresectable BRAF wild-type melanoma who have either progressed following previous treatment of immunotherapy, or are not eligible for immunotherapy; patients are defined as \BRAF wild-type\ if they test negative for V600 mutations based on a Clinical Laboratory Improvement Amendments (CLIA) certified assay
Patient has disease that tests positive for BRAF V600 mutations based on the results of a CLIA certified assay
Histologically-confirmed metastatic melanoma (Stage IV), carrying BRAF V600E or V600K mutation as determined by testing certified for clinical diagnostic purposes. Previously performed certified BRAF testing is acceptable. If no prior BRAF mutation testing results are available, testing of a distant metastasis is preferred, but testing of a regional metastasis or primary tumor is also acceptable
Only patients with v-raf murine sarcoma viral oncogene homolog B (BRAF) V600E mutated tumors will be enrolled
B2: Recurrent or unresectable low grade gliomas with BRAF tandem duplication with fusion
B4: BRAF V600 mutant tumors.
Tumors that have been documented by CLIA or equivalent certified laboratory test to harbor BRAF V600 mutation at diagnosis or relapse
BRAF V600 mutation-positive tumor as confirmed in a Clinical Laboratory Improvement Amendments (CLIA)-approved laboratory or equivalent (the local BRAF testing may be subject to subsequent verification by centralized testing; centralized testing can confirm V600E and V600K mutations only).
Melanoma must be documented to contain a v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600 mutation by a Clinical Laboratory Improvement Amendments (CLIA) approved assay
Measurable metastatic melanoma that expresses the V to E v-raf murine sarcoma viral oncogene homolog B (BRAF) mutation and V to K BRAF mutation assessed in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory
Must have histologically confirmed cutaneous metastatic melanoma (Stage IV) that is BRAF mutation-positive (V600 E/K) as determined via central testing with a BRAF mutation assay.
BRAF mutation positive melanoma or colorectal cancer; other BRAF mutation positive tumor types may be considered.
Presence of BRAF V600E mutation in tumor tissue
Patients with either unresectable Stage IIIc or Stage IV metastatic melanoma positive for the BRAFV600 mutation or other malignant tumor type that harbors a V600-activating mutation of BRAF, as determined by results of cobas® 4800 BRAF V600 mutation test or a DNA sequencing method, and who have no acceptable standard treatment options
BRAF V600E mutation
Patients with melanoma must also meet the following criteria: a. If melanoma is BRAF wild-type or has BRAF mutations that are not amenable to BRAF inhibitor therapy, and the patient is a candidate for immunotherapy, must have received ipilimumab; b. If melanoma is positive for the V600E or V600K BRAF mutation, must have received at least one line of prior therapy with a BRAF-specific inhibitor; either alone or in combination.
BRAF V600E mutation detected in the primary tumor or the recurrent/persistent tumor