Patients must have BRAF VE or BRAF VK 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 V 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 V mutations in melanoma include: THxID BRAF Detection Kit and Cobas  BRAF V Mutation Test)
Histologically proven papillary craniopharyngioma as documented by central pathology review with positive BRAF VE mutation by IHC
Group : Melanoma: All patients must have been tested for BRAF mutations. Patients with V 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.
If BRAF mutation status is unknown, before randomization the subject must have BRAF testing performed using an approved assay method.
For Phase a, subjects with one of the following tumor types will be enrolled: i. Urothelial cancer with HER or HER mutation ii. Biliary tract cancer with HER or HER mutation iii. Breast cancer with HER or HER mutation iv. Breast cancer with HER amplification or overexpression v. NSCLC with HER or HER mutation vi. CRC with HER mutation or amplification vii. Other tumors with HER mutation/amplification/overexpression or HER mutation (gastric/GEJ, endometrial).
No known activating mutations in KRAS, NRAS, HRAS and BRAF
Patients with melanoma should have unresectable or metastatic disease; melanoma patients with BRAF VE or VK mutation-positive melanoma who have previously received a BRAF inhibitor with or without a MEK inhibitor) are eligible
Patients with unknown BRAF mutation status may enroll so long as mutation testing is planned to be performed within  days of Cycle  Day  First-line NSCLC (pembrolizumab only)
Tumors harboring known activating KRAS, NRAS, HRAS, BRAF or PTPN (SHP) mutations.
Malignancy of non-squamous histology that carries a BRAF, KRAS, NRAS or HRAS mutation(s).
BRAF mutation in loci other than V (BRAF nonV MUT) or BRAF fusion detected by genetic testing of the primary tumor or regional/distant metastasis
BRAF mutation-positive (V E or K) melanoma for Parts ,  and , or for Parts , ,  and  only BRAF mutation-negative (wild type) melanoma with documented progression of >= measurable lesion after prior therapy (if prior therapy was received). The inclusion criterion does not apply to participants with solid tumors in Parts  and  (dose confirmation only).
Prior systemic therapy (for participants who are BRAF mutation-positive), or BRAF mutation-negative and has received > prior systemic therapy for metastatic melanoma
BRAF mutation-positive and has received prior systemic therapy with ipilimumab or other anti-cytotoxic T-lymphocyte antigen  (CTLA-) blocking antibodies. The BRAF exclusion criterion does not apply to participants with solid tumor in Parts  and  (dose confirmation only).
Patients must have histologically confirmed, BRAF-mutant (VE/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 V mutations in melanoma include: THxID BRAF Detection Kit and Cobas  BRAF V Mutation Test)
BRAF V mutation-positive malignancy
For enrollment to the phase I portion: participants must have a histologically confirmed melanoma with a BRAF VE or BRAF VK 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 VE or BRAF VK 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
PHASE II: Patients with measurable radiographically recurrent or radiographically progressive disease that is measurable in at least two dimensions on imaging after standard up-front therapy as defined in the following three strata below will be eligible\r\n* Stratum : patients with radiographically recurrent or radiographically progressive low-grade gliomas with a BRAF KIAA (or similar) truncated fusion duplication not previously treated with a BRAF or MEK inhibitor\r\n* Stratum : patients with NF and radiographically recurrent or radiographically progressive LGG (NF may be defined clinically or genetically) not previously treated with a BRAF or MEK inhibitor\r\n* Stratum : patients with radiographically recurrent or radiographically progressive tumors thought to involve the RAS/RAF/MEK/ERK pathway but not included in Stratum  or ; this includes any radiographically recurrent or radiographically progressive LGG not included in Stratum  or  (i.e., any LGG without a BRAF truncated fusion in a patient without NF), any CNS tumor other than LGG in a patient with NF, and any other CNS or solid tumor (regardless of grade) with a documented activating BRAF, NRAS, or KRAS mutation
Has testing for a BRAF mutation prior to study entry
Have documentation of V-activating BRAF mutation status or consent to BRAF V mutation testing during the screening period.
Patients whose melanomas harbor a BRAF VE or VK 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 VE or BRAF VK 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 VE or BRAF VK 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 BRAFVE and BRAF Ins T screening test
Part B: Have metastatic melanoma carrying BRAF mutation, refractory/relapsed after treatment with Raf and/or MEK inhibitors
Only patients with v-raf murine sarcoma viral oncogene homolog B (BRAF) VE or VK mutated tumors will be enrolled
Patients whose BRAF VE mutation status is unknown, have the BRAF VE mutation and are responding to a BRAF inhibitor or MEK inhibitor therapy, or have the BRAF VE 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^E mutation and BRAF KIAA fusion assessments)\r\n* All patients who are candidates for enrollment in stratum  based on their tumor histology must be pre-screened\r\n* Screening may be applied to potential stratum  and  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 Womens 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 BRAFVE mutation and BRAF KIAA 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 (VE/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 V mutations in melanoma include: THxID BRAF detection kit and Cobas  BRAF V mutation test).
For Dose-Expansion Phase: Patients must have histologically confirmed, BRAF-mutant (VE/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 V mutations in melanoma include: THxID BRAF detection kit and Cobas  BRAF V mutation test).
Has previously documented evidence of ALK fusion, ROS fusion, BRAF VE mutation, RET rearrangement, HER mutation, MET amplification, or MET exon  skipping mutation. No new testing for these genomic alterations is required for Screening.
Additional criteria for escalation cohorts: A) patients must have Ras pathway activation (RPA) (including KRAS, NRAS, NF, HRAS, and BRAF); B) prior treatment with MEK inhibitors and/or PARP inhibitors is allowed
Participants must have BRAFV-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 V mutations in melanoma include: THxID BRAF Detection Kit and Cobas  BRAF V Mutation Test)
Patients are included regardless of KRAS/NRAS, BRAF, p, or microsatellite instability (MSI) status
Harboring a mutation in the BRAF oncogene or the KRAS or the NRAS oncogene
Documented HER mutation.
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 V 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
Patients who have been previously treated for metastatic melanoma may be included (e.g. prior treatment with v-raf murine sarcoma viral oncogene homolog B [BRAF] inhibitors and/or ipilimumab will be allowed), provided that they have had a three week washout prior to signing consent and have not been treated with a PD- blocking antibody
One of the following:\r\n* Documentation of BRAF VE 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 V mutational status
Participants with age greater than or equal to (>=)  years with either unresectable Stage IIIC or Stage IV metastatic melanoma positive for the BRAF V mutation, or other malignant tumor types that harbor a V-activating mutation of BRAF
CAPMATINIB INCLUSION CRITERIA: Documentation of absence of activating and targetable BRAF or NRAS point mutations
CERITINIB 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 VE melanoma patients who have failed BRAF inhibitors\r\n*** Note: Patients with pancreatic cancer, colorectal cancer, and BRAF VE melanoma patients who have failed BRAF inhibitors are allowed to enroll in the moderate and severe cohorts provided the patients: ) sign a separate consent form which outlines the extremely limited activity observed in prior studies, and ) are consented to the study by a protocol-specified designee who is not their longitudinal oncologist
B-Raf proto-oncogene, serine/threonine kinase (BRAF) VE 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 patients thyroid tumors (primary tumor, recurrent tumor, or metastasis) does not have any of the following mutations:\r\n* Mutation at V of the v-raf murine sarcoma viral oncogene homolog B (BRAF) gene\r\n* Mutation in NRAS or KRAS or HRAS at G, G, or Q\r\n* These patients will be designated BRAF/RAS wild type (WT)
Patients must have histologically confirmed, BRAF-mutant (VE/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 V mutations in melanoma include: THxID BRAF Detection Kit and Cobas  BRAF V Mutation Test)
Any patient with metastatic melanoma from any site whose tumor is BRAF VE mutation (VEBRAF) 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 B (BRAF) V mutation status
Group : BRAF mutant melanoma (Part B)
Patients whose tumors harbor the BRAF VE 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 , , , , , and ) and in BRAF codon , based on tumor tissue taken from primary or metastatic site and tested for biomarkers
Confirmed wild-type status in KRAS exons , , and ; NRAS exons , , and ; 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  weeks prior to starting study therapy
In cohort , must have EGFR SR or other ectodomain mutation detected from circulating tumor DNA from plasma collected after progression to prior cetuximab; may have a concomitant mutation in KRAS, NRAS, or BRAF, if there is at least a -fold higher allele frequency of the most prevalent EGFR mutation than the most prevalent KRAS/NRAS/BRAF mutation
In cohort , must have one or more mutations found in KRAS exon , , or ; NRAS exon , , or ; BRAF codon ; may have a concomitant EGFR ectodomain mutation, if the most prevalent EGFR ectodomain mutation does not have over a -fold higher allele frequency than the most prevalent KRAS/NRAS/BRAF mutation
In cohort , 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 B (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) VE mutations must have received and progressed on specific BRAF inhibitor therapy
Patients must have BRAFVE or BRAFVK 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 V mutations in melanoma include: THxID BRAF Detection Kit and Cobas  BRAF V Mutation Test)
Patients must have measurable and histologically or cytologically confirmed thyroid cancer with a BRAF VE or VK (c.  T to A and c._TG>AA) mutation that is not considered curable by surgery; confirmation will be done at Memorial Sloan Kettering (MSK); only tumors with a BRAFVE or BRAFVK 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  BRAF V Mutation Test)
Tumor may have a v-raf murine sarcoma viral oncogene homolog B (B-RAF) V 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 V 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) VE, D or K mutation by Cobas pyrosequencing assay or equivalent
Documentation of VE-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 V positive\r\n* Note: prior therapy with ipilimumab not required
Patients may not have received prior MEK, v-Ki-ras Kirsten rat sarcoma viral oncogene homolog (KRAS), or v-raf murine sarcoma viral oncogene homolog B (BRAF) inhibitor therapy
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 B(BRAF) mutational analysis
Either treatment nave or received only one line of systemic anticancer therapy if v-raf murine sarcoma viral oncogene homolog B (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 V mutation status of the current primary tumor or involved lymph node determined to be positive using the cobas BRAF V 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 B (BRAF) V 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 V mutation in their metastatic tumor
Patients must have received a biologic therapy (interleukin  or ipilimumab) and a BRAF and/or MEK inhibitor (if tumor contains the VE or VK 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 Ve/k BRAF mutation or patient with autoimmunity, thus not eligible for biologic therapy)
Evaluation of v-raf murine sarcoma viral oncogene homolog B (BRAF)V mutation status
The tumor tissue must have been determined to be KRAS, NRAS, BRAF, PIKCA wild-type by central CLIA testing.
Must have a a BRAF VE 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 VE mutation by a sponsor designated central reference laboratory using a sponsor designated assay
Presence of BRAF VE or VK mutation in tumor tissue prior to randomization
Willing to provide tissue as required per protocol for central BRAF^VX mutation testing\r\n* NOTE: patients with prior BRAF^X testing that demonstrate a mutation at VX 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  BRAF mutation test and other CLIA-certified assays available at participating institutions
Patients with unknown BRAF^X status: histologically confirmed melanoma, papillary thyroid, cholangiocarcinoma or testicular cancer that is metastatic or unresectable and for which the investigator feels a BRAF^X targeted agent is a reasonable treatment\r\n* NOTE: patient must be screened by central BRAF testing and must demonstrate a V mutation prior to start of study agent\r\n* Note: other tumor types without known BRAF^X mutations will not be eligible for central testing
Patients with known BRAF^VX mutation: patients must have BRAF^VX 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 V 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 V position
Group : Patients with BRAF mutated melanoma who have progressed on, or are refractory to BRAF and/or MEK inhibitors
If archived tissue is unavailable for KRAS, NRAS, or BRAF mutation testing, or patient refuses a fresh biopsy for mutation analysis
Histologically confirmed VE or VK BRAF mutant melanoma
Presence of BRAF mutation or genes fusion involving BRAF in tumor tissue
Unknown BRAF status
A documented BRAF VE or BRAF VK 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 VE or VK mutation-positive melanoma must have progressed on, or were intolerant to, prior BRAF- or MEK-inhibitor therapy
Histological diagnosis of unresectable or metastatic colorectal cancer which is KRAS and NRAS mutation negative (wild type); patients with any known mutation in KRAS or NRAS codons , , , , , or  will be excluded; mutations of KRAS and NRAS codons not listed above are allowed; biopsy of metastatic lesion is not required
Any known mutation in KRAS or NRAS codons , , , ,, or 
Confirmed RAS mutation (neuroblastoma RAS viral [v-ras] oncogene homolog [NRAS] or Kirsten rat sarcoma viral oncogene homolog [KRAS]) or confirmed PTPN mutation, measured on peripheral blood or bone marrow aspirate as part of screening prior to study enrollment; mutation status must be confirmed within  days of initiation of therapy
Positive proto-oncogene B-Raf (BRAF) mutation result (Cobas  BRAF V Mutation Test)
SELUMETINIB ARM: Patients must have one of the following as determined by analysis of the primary tumor or a metastatic site in a CLIA certified laboratory:\r\n* Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation or\r\n* Neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) mutation or\r\n* Harvey rat sarcoma viral oncogene homolog (HRAS) mutation or\r\n* V-raf murine sarcoma viral oncogene homolog B (BRAF) mutation
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 V.
Written documentation of KRAS wild-type status and BRAFV-mutation with RNF mutation and/or RSPO fusion
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 V mutations based on a Clinical Laboratory Improvement Amendments (CLIA) certified assay
Patient has disease that tests positive for BRAF V mutations based on the results of a CLIA certified assay
Histologically-confirmed metastatic melanoma (Stage IV), carrying BRAF VE or VK 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) VE mutated tumors will be enrolled
Tumor must be wild type for the v-Ki-ras Kirsten rat sarcoma viral oncogene homolog (KRAS) and BRAF oncogenes, and must have known PIKCA, AKT mutation status and PTEN expression status
Not a candidate for targeted therapy with BRAF or combined BRAF/MEK inhibitors (e.g., failed or did not tolerate prior therapy, BRAF V wild-type or due to drug unavailability or standard of care)
B: Recurrent or unresectable low grade gliomas with BRAF tandem duplication with fusion
B: BRAF V mutant tumors.
Tumors that have been documented by CLIA or equivalent certified laboratory test to harbor BRAF V mutation at diagnosis or relapse
BRAF V 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 VE and VK mutations only).
Melanoma must be documented to contain a v-raf murine sarcoma viral oncogene homolog B (BRAF) V 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 (V 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.
Patients must have KRAS/NRAS/BRAF wild-type colorectal cancer
Presence of BRAF VE mutation in tumor tissue
Patients with either unresectable Stage IIIc or Stage IV metastatic melanoma positive for the BRAFV mutation or other malignant tumor type that harbors a V-activating mutation of BRAF, as determined by results of cobas  BRAF V mutation test or a DNA sequencing method, and who have no acceptable standard treatment options
BRAF VE 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 VE or VK BRAF mutation, must have received at least one line of prior therapy with a BRAF-specific inhibitor; either alone or in combination.
Has previously documented evidence of ALK fusion, ROS fusion, BRAF VE mutation, RET rearrangement, HER mutation, MET amplification, or MET exon  skipping mutation. No new testing for these genomic alterations is required for Screening.
BRAF VE mutation detected in the primary tumor or the recurrent/persistent tumor
Prior treatment with MEK or v-raf murine sarcoma viral oncogene homolog B (BRAF) inhibitors