COMPOUNDS FOR THE TREATMENT OF DISEASES AND DISORDERS ASSOCIATED WITH BRAF

Abstract

A compound of Formula I: (see Formula) I or a pharmaceutically acceptable salt thereof is provided herein, wherein R1, R2, R3, R4, R5, R6, R7 and L are as defined herein, for the treatment of BRAF-associated diseases and disorders, including BRAF-associated tumors.

Description

COMPOUNDS FOR THE TREATMENT OF ASSOCIATED DISEASES AND DISORDERS ABRAF CROSS REFERENCE TO RELATED REQUESTS This application claims the benefit of priority to U.S. Provisional Application No. 63 / 036,522, filed June 9, 2020, U.S. Provisional Application No. 63 / 116,204, filed Nov. 20, 2020, and U.S. Provisional Application No. U.S. Provisional No. 63 / 175,655, filed April 16, 2021, the contents of which are fully incorporated herein by reference. FIELD OF THE INVENTION This disclosure relates to novel quinazolinone compounds or a pharmaceutically acceptable salt thereof, to pharmaceutical compositions comprising such compounds and salts, and to methods of using such compounds, salts and compositions for the treatment of abnormal cell growth, which includes cancer, in a subject. BACKGROUND OF THE INVENTION The present disclosure relates to quinazolinones for the treatment of BRAF-associated diseases and disorders, including BRAF-associated tumors, including BRAF-associated malignant and benign CNS tumors and BRAF-associated malignant extracranial tumors. The BRAF protein, a member of the RAF family of serine / threonine kinases, participates in the Ras-Raf-MEK extracellular signal-regulated kinase (ERK) cascade or the Ras-Raf-MEK-activated protein kinase signaling pathway. mitogens (MAPK) / ERK that affects cell division and differentiation. Mutations in the BRAF gene can cause uncontrolled growth and subsequent tumor formation. More than 100 unique mutations in the BRAF gene have been identified in cancer (Cerami, E., etaL, Cancer Discov. 2012, 2, 401-404). These mutations lead to ERK activation through different functional mechanisms and have been grouped into three classes, two of which are called class I and class II mutations, based on their dependence on dimerization and activation by RAS. for activity; These properties determine its sensitivity to RAF inhibitors (Yao, A., etaL, Cancer Cell 2015, 28, 370-383). Activating BRAF class I mutations, such as V600E and / or V600K, have been found in human cancers, such as melanoma, colorectal cancer, thyroid cancer, non-small cell lung cancer, ovarian cancer, carcinoma of renal cells and metastatic cancers of these and primary brain tumors. Class I mutations, such as the BRAF V600 mutants, signal as RAS-independent active monomers. BRAF class II mutations include non-V600 mutations, which activate MEK through dimerization but without a RAS requirement (Yao, A., etaL, Cancer Cell 2015, 28, 370-383). These class II mutations undergo constitutive RAS-independent dimerization, leading to increased ERK activation with low RAS activity due to negative feedback. Common class II point mutations include G469A / V / R, K601E / N / T, and L597Q / V. Non-V600 mutants are resistant to BRAF class I inhibitors, such as vemurafenib. Non-V600 BRAF mutants have also been found in many cancer types and are more common than V600 mutations in certain tumor types. Non-V600 BRAF mutations are found in 5-16% of melanomas, as well as a variety of other tumor types (Siroy AE, et al., J Invest Dermatol. 2015;135:508-515; Dahlman KB, et al. Cancer Discov 2012;2:791-797). Approximately 50-80% of BRAF mutations in non-small cell lung cancer and 22-30% in colorectal cancer encode non-V600 mutations. (Jones JC, et al. J Clin Oncol. 2017;35:2624-2630; Paik PK, et al. J Clin Oncol. 2011;29:2046-2051). BRAF class II mutations such as G469A, G469R, G469V, K601E, K601N, K601T, L597Q and L597V have been identified in gliomas (Schreck, KC et a / ., Cancer (2019) 11: 1262) and other tumors such as breast cancer, small cell lung cancer, pancreatic cancer, thyroid cancer, prostate cancer, adenoid cystic carcinoma, appendiceal cancer, small intestine cancer, head and neck squamous cell carcinoma, and angiosarcoma (Sullivan, RJ, Cancer Discov, February 1, 2018 (8) (2) 184 -195). BRAF class II mutations have also been identified in metastatic cancers (Dagogo-Jack, I., Clin Cancer Res. September 2018; Schirripa, M., Clin Cancer Res., May 2019; Menzer, C., J. Clin Oncol 2019, 37(33):3142-3151). Furthermore, BRAF in-frame deletions can function as class II mutations. For example, acquired resistance has been observed in patients treated with BRAF V600 inhibitors. Acquired resistance mechanisms include alternative splicing. BRAF splice variants encode an active kinase, but lack an intact RAS-binding domain. Vemurafenib-resistant cells have been found to express variant forms of BRAF V600E that lack exons spanning the RAS binding domain, specifically, lacking exons 4-10, exons 4-8, exons 2-8, or exons 2-10 (Poulikakos, P.I, eta / ., Nature, 480(7377):387390. Currently, there are no effective targeted treatments available for patients harboring non-V600 BRAF alterations or BRAF inhibitor resistance mutations. Although certain inhibitors of BRAF V600 mutations produce excellent extracranial responses, a type of cancer can still develop brain metastases during or after treatment with BRAF inhibitors (Oliva I.C.G, eta / ., Annals of Oncology, 29: 1509-1520 ( 2018)). It is estimated that 20% of all cancer subjects will develop brain metastases, and the majority of brain metastases will occur in those with melanoma, colorectal cancer, lung cancer, and renal cell carcinoma (Achrol AS, etal., Nature Reviews ( 2019), 5:5, pages 126). Although these are the types most likely to do so, any type of cancer could spread to the brain. The development of brain metastases remains a substantial contributor to overall cancer mortality in subjects with advanced-stage cancer because the prognosis remains poor despite multimodal treatments and advances in systemic therapies, including combinations of surgery, radiotherapy , chemotherapy, immunotherapy and / or targeted treatments. BRAF has also been identified as a potential target for the treatment of primary brain tumors. The prevalence of the BRAF-V600E mutation in primary brain tumors has been reported by Schindler et a / . (Acta Neuropathol 121(3):397-405, 2011) from the analysis of 1,320 tumors of the central nervous system (CNS) and by Behling et!. (Diagn Pathol 11(1):55, 2016), who analyzed 969 CNS tumors in pediatric and adult populations. These studies, in combination with others, report the presence of BRAF-V600E mutations in several types of cancer, including papillary craniopharyngiomas, pleomorphic xanthoastrocytomas (PXA), gangliogliomas, astroblastomas, and others. (Behling etal., Diagn Pathol 11 (1):55, 2016; Brastianos etal., Nat Genet46 (2):161-165, 2014; Dougherty etal., NeuroOncol 12 (7):621-630, 2010; Lehman etal. / ., Neuro Oncol 19 (1):31-42, 2017; Mordechai etaL, Pediatr Hematol Oncol 32 (3):207-211, 2015; eta / ., Acta Neuropathol 121 (3):397-405, 2011). Cancer types, including metastatic cancers, have also been described that have BRAF fusion proteins (J.S. Ross, eta!., Int. J. Cancer: 138, 881-890 (2016)). The blood-brain interfaces comprise the endothelium of the brain microvessel that forms the blood-brain barrier (BBB) ​​and the epithelium of the choroid plexuses that form the blood-CNS barrier (BCSFB). The blood-brain barrier (BBB) ​​is a highly selective physical, metabolic, and transport barrier that divides the CNS from the blood. The BBB can prevent certain drugs from entering brain tissue and is a limiting factor in the delivery of many peripherally administered agents into the CNS. Many drugs commonly used to treat cancer cannot cross the BBB. This means that the drugs cannot penetrate the brain and therefore cannot effectively inactivate cancer cells in the brain. Current treatments for subjects with brain tumors include surgical resection, radiotherapy, and / or chemotherapy with agents such as temozolomide and / or bevacizumab. However, treatment of brain cancers by surgery is not always possible or desirable; for example, the tumor may be inaccessible, or the subject may be unable to withstand the trauma of neurosurgery. Furthermore, radiotherapy and treatment with cytotoxic agents are known to have undesirable side effects. For example, there is growing evidence that the use of temozolomide can itself induce mutations and worsen prognosis in a significant fraction of subjects (B. E. Johnson et a / ., Science 343: 189-193 (2014)), and the Bevacizumab labeling has boxed warnings for gastrointestinal perforation, surgical and wound healing complications, and bleeding. Kinase inhibitors are useful in treating many peripheral cancers. However, due to their structural characteristics, many kinase inhibitors such as BRAF inhibitors (e.g., vemurafenib and dabrafenib) are substrates of active transporters such as P-glycoproteins (P-gp) or breast cancer resistance protein. (BCRP). For example, dabrafenib has been reported to have an MDR1 efflux ratio of 11.4, a BCRP efflux ratio of 21.0, and a whole brain to plasma ratio of 0.023; no brain-to-plasma free ratio was reported (Mittapalli, RK, et al!., J Pharmacol. Exp Ther 344:655-664, March 2013), and vemurafenib has been reported to have a free brain to plasma ratio. MDR1 efflux of 83, a BCRP efflux ratio of 495, and a total brain to plasma ratio of 0.004; no brain-to-plasma free ratio was reported (Mittapalli, RK. eta / ., J Pharmacol. Exp Ther 342:33-40 (March 2012). Since both P-gp and BCRP are expressed in the endothelial cells lining blood-brain capillaries, the activity of both P-gp and BCRP at the BBB plays a critical role in preventing the distribution of most of kinase inhibitors to the brain parenchyma. Therefore, kinase inhibitors are generally not suitable for use in treating tumors or cancers in the brain, which is protected by the BBB. Therefore, there remains a need for treatment of tumors carrying BRAF mutations, including class I and class II mutations, which include resistance mutations. Furthermore, treatments for CNS tumors, including CNS tumors carrying BRAF mutations, including resistance mutations, remain an unmet need. MA / a / ZUZZ / UJ 0 / U J BRIEF DESCRIPTION OF THE INVENTION Accordingly, a compound of Formula I is provided herein: ινΐΛ / a / zuzz / u 1 o / u j or a pharmaceutically acceptable salt thereof, wherein: L is NH or O; R1 is C1-C6 alkyl, C1-C6 deuteroalkyl, C1-C6 fluoroalkyl, C3-C6 cycloalkyl, (C3-C6 cycloalkyl)CH2-, (C1-C6 alkoxy)Cl-C6 alkyl-, Ar1, Ar1CH2-, hetAr1or hetCyc1; Ar1 is phenyl which is optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from halogen and C1-C3 alkyl; hetAr1 is a 5-6 membered heteroaryl ring having 1 or 2 ring nitrogen atoms and which is optionally substituted with 1, 2 or 3 substituents independently selected from halogen and C1-C3 alkyl; hetCyc1 is a 4-6 membered saturated monocyclic heterocyclic ring having one ring oxygen atom; R2is -CH3, -CH2CH3, -CH=CH2, F, CI, Br or CN; R3is F or CI; R4is H or F; R5is H, F or CI; R6is C1-C6 alkyl, and R7is C1-C6 alkyl, hetCyc2o C3-C6 cycloalkyl, or R6and R7 together with the nitrogen atom to which they are attached form a saturated ring system selected from (i) a 4-6 membered monocyclic ring optionally having a second heteroatom of ring which is O, wherein said ring is optionally substituted with 1 or 2 substituents independently selected from F, -OH, -OCH3, -OCHF2, -OCD3, -CH3, -CH2CH3, -CH2OCH3, -CH2OCH2F, -CH2OCHF2, - CH2OCF3, -OCF3, -OCH2CH3, and CN, (i) a 6-7 membered fused bicyclic ring optionally substituted with 1 or 2 substituents independently selected from F and -CH3, (iii) a 6-7 bridged ring members and (iv) a 6-8 membered spirocyclic ring; and hetCyc2 is a saturated 5-6 membered monocyclic heterocyclic ring having 1 or 2 ring heteroatoms independently selected from N and O; as long as the compound is not: N-(2-chloro-3-((3,5-dimethyl-4-oxo-3,4-dihydroquinazolin-6-l)amino)-4-fluorophen l)pyrrolidin-lsulfonamide, (R)-N-(2-chloro-3-((3,5-dimethyl-4-oxo-3,4-dihydroquinazolin- 6-l)amino)-4-fluorophenyl)-3fluoropyrrolidin-l-sulfonamide, or N-(2-chloro-3-((3,5-dimethyl-4-oxo-3,4-dihydroquinazolin-6-l)amino)-4-fluorophen l)-N-ethyl-Nmethylamino-l-sulfonamide. Also provided herein is a compound of Formula I-A or a pharmaceutically acceptable salt thereof, wherein: L is NH or O; R1is C1-C6 alkyl, C1-C6 deuteroalkyl, C1-C6 fluoroalkyl, C3-C6 cycloalkyl, (C3-C6 cycloalkyl)CH2-, (C1-C6 alkoxy)Cl-C6 alkyl-, Ar1, Αγ^Ης-, hetAr1o hetCyc1; Ar1 is phenyl which is optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from halogen and C1-C3 alkyl; hetAr1 is a 5-6 membered heteroaryl ring having 1 or 2 ring nitrogen atoms and which is optionally substituted with 1, 2 or 3 substituents independently selected from halogen and C1-C3 alkyl; hetCyc1 is a saturated 4-6 membered monocyclic heterocyclic ring having one ring oxygen atom; R2is -CH3, -CH2CH3, -CH=CH2, F, Cl, Br or CN; R3is F or Cl; R4is H or F; R5 is H, F or Cl; R6is C1-C6 alkyl, and R7is C1-C6 alkyl, hetCyc2o C3-C6 cycloalkyl, or R6and R7 together with the nitrogen atom to which they are attached form a saturated ring system selected from (i) a 4-6 membered monocyclic ring optionally having a second heteroatom of ring that is O, wherein said ring is optionally substituted with 1 or 2 substituents independently selected from F, -OH, -OCH3, -OCF2H, -OCD3, -CH3 and -CH2CH3, (ii) a fused bicyclic ring of 6- 7 membered optionally substituted with 1 or 2 substituents independently selected from F and -CH3, (iii) a 6-7 membered bridged ring and (iv) a 7 membered spirocyclic ring; and hetCyc2 is a saturated 5-6 membered monocyclic heterocyclic ring having 1 or 2 ring heteroatoms independently selected from N and O; as long as the compound is not: N-(2-chloro-3-((3,5-dimethyl-4-oxo-3,4-dihydroquinazolin-6-l)amino)-4-fluorophen ¡l)pyrrolidin-lsulfonamide, (R)-N-(2-chloro-3-((3,5-dimethyl-4-oxo-3,4-dihydroquinazolin-6-¡l)am no)-4-fluorophenyl)-3fluoropyrrolidin-l-sulfonamide, or N-(2-chloro-3-((3,5-dimethyl-4-oxo-3,4-dihydroquinazolin-6-l)amino)-4-fluorophen l)-N-ethyl-Nmethylamino-l-sulfonamide. Also provided herein is a compound of Formula II: or a pharmaceutically acceptable salt thereof, wherein: L is NH or O; R1 is C1-C6 alkyl or C1-C6 fluoroalkyl; R2is -CH3, -CH2CH3, -CH=CH2, F, Cl, Br or CN; R3is F or Cl; R4is H or F; R5 is H, F or Cl; R6is C1-C6 alkyl, and R7is C1-C6 alkyl, hetCyc2o C3-C6 cycloalkyl, or R6and R7 together with the nitrogen atom to which they are attached form a saturated ring system selected from (i) a 4-6 membered monocyclic ring optionally having a second heteroatom of ring that is O, wherein said ring is optionally substituted with 1 or 2 substituents independently selected from F, -OH, -OCH3, -OCHF2, -OCD3, -CH3, -CH2CH3, -CH2OCH3, -CH2OCH2F, -CH2OCHF2, - CH2OCF3, -OCF3, -OCH2CH3, and CN, (i) a 6-7 membered fused bicyclic ring optionally substituted with 1 or 2 substituents independently selected from F and -CH3, (iii) a 6-7 bridged ring members and (iv) a 6-8 membered spirocyclic ring; and hetCyc2 is a saturated 5-6 membered monocyclic heterocyclic ring having 1 or 2 ring heteroatoms independently selected from N and O; as long as the compound is not: N-(2-chloro-3-((3,5-dimethyl-4-oxo-3,4-dihydroqunazolin-6-yl)amino)-4-fluorophenyl)pyrrole d¡n-lsulfonamide, (R)-N-(2-chloro-3-((3,5-dimethyl-4-oxo-3,4-d¡hydroquinazolin-6-¡l)am¡ no)-4-fluorophenyl)-3fluoropyrrolidin-l-sulfonamide, or N-(2-chloro-3-((3,5-dimethyl-4-oxo-3,4-dihydroquinazolin-6-l)amino)-4 -fluorophenyl)-N-ethyl-Nmethylamino-l-sulfonamide. Also provided herein is a compound of Formula III or a pharmaceutically acceptable salt thereof, wherein: L is NH or O; R1 is C1-C6 alkyl, C1-C6 deuteroalkyl, C1-C6 fluoroalkyl, C3-C6 cycloalkyl, (C3-C6 cycloalkyl)CH2-, (C1-C6 alkoxy)Cl-C6 alkyl-, Ar1, AHCFh-, hetAr1or hetCyc1; Ar1 is phenyl which is optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from halogen and C1-C3 alkyl; hetAr1 is a 5-6 membered heteroaryl ring having 1 or 2 ring nitrogen atoms and which is optionally substituted with 1, 2 or 3 substituents independently selected from halogen and C1-C3 alkyl; hetCyc1 is a saturated 4-6 membered monocyclic heterocyclic ring having one ring oxygen atom; R2is -CH2CH3, -CH=CH2, F, Cl, Br or CN; R3is F or Cl; R4is H or F; R5 is H, F or Cl; R6is C1-C6 alkyl, and R7is C1-C6 alkyl, hetCyc2o C3-C6 cycloalkyl, or R6and R7 together with the nitrogen atom to which they are attached form a saturated ring system selected from (i) a 4-6 membered monocyclic ring optionally having a second heteroatom of ring which is O, wherein said ring is optionally substituted with 1 or 2 substituents independently selected from F, -OH, -OCH3, -OCHF2, -OCD3, -CH3, -CH2CH3, -CH2OCH3, -CH2OCH2F, -CH2OCHF2, - CH2OCF3, -OCF3, -OCH2CH3, and CN, (i) a 6-7 membered fused bicyclic ring optionally substituted with 1 or 2 substituents independently selected from F and -CH3, (i¡) a 6-bridged ring -7 members and (iv) a 6-8 membered spirocyclic ring; and hetCyc2 is a saturated 5-6 membered monocyclic heterocyclic ring having 1 or 2 ring heteroatoms independently selected from N and O. Also provided herein is a compound of Formula IV or a pharmaceutically acceptable salt thereof, wherein: L is NH or O; R1is C1-C6 alkyl, C1-C6 deuteroalkyl, C1-C6 fluoroalkyl, C3-C6 cycloalkyl, (C3-C6 cycloalkyl)CH2-, (C1-C6 alkoxy)Cl-C6 alkyl-, Ar1, Αγ^Η2-, hetAr1o hetCyc1; Ar1 is phenyl which is optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from halogen and C1-C3 alkyl; hetAr1 is a 5-6 membered heteroaryl ring having 1 or 2 ring nitrogen atoms and which is optionally substituted with 1, 2 or 3 substituents independently selected from halogen and C1-C3 alkyl; hetCyc1 is a saturated 4-6 membered monocyclic heterocyclic ring having one ring oxygen atom; R2is -CH3, -CH2CH3, -CH=CH2, F, Cl, Br or CN; R3is F or Cl; R4is H or F; R5 is H, F or Cl; R6is C1-C6 alkyl, and R7is C1-C6 alkyl, hetCyc2o C3-C6 cycloalkyl, or R6and R7 together with the nitrogen atom to which they are attached form a saturated ring system selected from (i) a 4-6 membered monocyclic ring optionally having a second heteroatom of ring that is O, wherein said ring is optionally substituted with 1 or 2 substituents independently selected from F, -OH, -OCH3, -OCHF2, -OCD3, -CH3, -CH2CH3, -CH2OCH3 / -CH2OCH2F, -CH2OCHF2, -CH2OCF3, -OCF3, -OCH2CH3, and CN, (ii) a 6-7 membered fused bicyclic ring optionally substituted with 1 or 2 substituents independently selected from F and -CH3, (i ¡) a 6-7 membered bridging ring and (iv) a 6-8 membered spirocyclic ring; and hetCyc2 is a saturated 5-6 membered monocyclic heterocyclic ring having 1 or 2 ring heteroatoms independently selected from N and O; where when R1 is methyl, L is NH, R3 is Cl, R4 is F, R5 is H, and R6 is methyl and R7 is ethyl, or R6 and R7 together with the nitrogen atom to which they are attached form a pyrrolidinyl or 3fluoropyrrolidinyl, then R2 is -CH2CH3, - CH=CH2, F, Cl, Br or CN. Also provided herein is a compound of Formula V or a pharmaceutically acceptable salt thereof, wherein: L is NH; R1 is C1-C6 alkyl; R2is F or Cl; R3es Cl; R4is F; R5is H; R6 and R7 together with the nitrogen atom to which they are attached form a saturated ring system selected from (i) a 4-6 membered monocyclic ring optionally having a second ring heteroatom which is O, wherein said ring is optionally substituted with 1 or 2 substituents independently selected from F, -OH, -OCH3, -OCHF2, -OCD3, -CH3, -CH2CH3, -CH2OCH3, -CH2OCH2F, -CH2OCHF2, -CH2OCF3, -OCF3, -OCH2CH3 and CN, and (iii ) a 67-member bridge ring. Also provided herein is a pharmaceutical composition comprising a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers. Also provided herein is a method of treating a BRAF-associated tumor in a subject in need of such treatment, wherein the method comprises administering to the subject a therapeutically effective amount of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. The compounds of the invention may be administered as single agents or may be administered in combination with other antineoplastic treatments, such as one or more additional antineoplastic treatments selected independently of one or more antineoplastic agents and / or surgery and / or radiotherapy. Also provided herein is a method of inhibiting metastasis associated with a BRAF-associated tumor in a subject in need of such treatment, wherein the method comprises administering to the subject a therapeutically effective amount of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. Also provided herein is a method for inhibiting BRAF kinase activity, in vitro or in vivo, wherein the method comprises administering to the subject a therapeutically effective amount of a compound of Formula I, Formula I-A, Formula II, Formula III , Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. Also provided herein is a method of inhibiting cell proliferation, in vitro or in vivo, wherein the method comprises contacting a cell with a therapeutically effective amount of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. Also provided herein is a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof for use in treatment. Also provided herein is a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof for use in the treatment of tumors. Also provided herein is a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof for use in inhibiting metastasis associated with a BRAF-associated tumor. Also provided herein is a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof for use in inhibiting the activity of BRAF kinase. Also provided herein is a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof for use in the treatment of a disease or BRAF-associated disorder (for example, a BRAF-associated tumor). Also provided herein is the use of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, as defined herein in the manufacture of a medicament for the treatment of a BRAF-associated tumor (e.g. a BRAF-associated malignant tumor or a BRAF-associated benign tumor). Also provided herein is the use of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, as defined herein. in the manufacture of a drug to inhibit metastasis associated with a BRAF-associated tumor. Also provided herein is a use of a compound of Formula I, Formula ΙΑ, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, as defined herein. in the manufacture of a drug to inhibit metastasis associated with a BRAF-associated tumor. Also provided herein is the use of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, as defined herein. , in the manufacture of a medicine for the treatment of a disease or disorder associated with BRAF. Also provided herein is a method of treating a BRAF-associated tumor in a subject in need thereof, wherein the method comprises (a) determining that the tumor is associated with a BRAF mutation; and (b) administering to the subject a therapeutically effective amount of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, or a composition pharmaceutical of this. Also provided herein is a pharmaceutical combination for treating a BRAF-associated tumor in a subject in need thereof, comprising (a) a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, and (b) a further antineoplastic agent, wherein the compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or the acceptable salt from a pharmaceutical point of view thereof, and the additional antineoplastic agent are formulated as separate compositions or doses for separate or sequential use for the treatment of BRAF-associated tumor, wherein the amounts of the compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, and the additional antineoplastic agent are together effective in the treatment of BRAF-associated tumor. Also provided herein is the use of said combination for use in the treatment of a BRAF-associated tumor. Also provided herein is a commercial package or product comprising such a combination as a combination preparation for separate or sequential use in the treatment of a BRAF-associated tumor in a subject in need thereof. Also provided herein are methods of treating a subject with a BRAF-associated tumor that include administration of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or an acceptable salt thereof. the pharmaceutical point of view of this, before, during or after the administration of another antineoplastic treatment (for example, surgery, radiotherapy and / or another anticancer drug). Also provided herein is a process for preparing a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. Also provided herein is a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, obtained by a compound preparation process such as is defined herein. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as customarily given to them by a person in the mid-level trade to whom the invention pertains. The methods and materials are described herein for use in the present invention; Other suitable methods and materials known in the art may also be used. The materials, methods and examples are illustrative only and not limiting. All publications, patent applications, patents, sequences, database entries and other references mentioned herein are incorporated by reference in their entirety. In the event of a conflict, this specification, including the definitions, will prevail. Other features and advantages of the invention will become apparent after analyzing the following detailed description and figures, and the claims. BRIEF DESCRIPTION OF THE FIGURES Figure 1 illustrates an X-ray powder diffraction (XRPD) pattern of the crystalline form (R)-N-(2-chloro-4-fluoro-3-((5-fluoro-3-methyl-4- oxo-3,4-dihydroquinazolin-6-yl)amino)phenyl)-3fluoropyrrolidin-l-sulfonamide, Form A. DETAILED DESCRIPTION OF THE INVENTION Provided herein is a compound of Formula I: or a pharmaceutically acceptable salt thereof, wherein: L is NH or O; R1 is C1-C6 alkyl, C1-C6 deuteroalkyl, C1-C6 fluoroalkyl, C3-C6 cycloalkyl, (C3-C6 cycloalkyl)CH2-, (C1-C6 alkoxy)Cl-C6 alkyl-, Ar1, Ar1CH2-, hetAr1or hetCyc1; Ar1 is phenyl which is optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from halogen and C1-C3 alkyl; hetAr1 is a 5-6 membered heteroaryl ring having 1 or 2 ring nitrogen atoms and which is optionally substituted with 1, 2 or 3 substituents independently selected from halogen and C1-C3 alkyl; hetCyc1 is a saturated 4-6 membered monocyclic heterocyclic ring having one ring oxygen atom; R2is -CH3, -CH2CH3, -CH=CH2, F, Cl, Br or CN; R3is F or Cl; R4is H or F; R5 is H, F or Cl; R6is C1-C6 alkyl, and R7is C1-C6 alkyl, hetCyc2o C3-C6 cycloalkyl, or R6and R7 together with the nitrogen atom to which they are attached form a saturated ring system selected from (i) a 4-6 membered monocyclic ring optionally having a second heteroatom of ring that is O, wherein said ring is optionally substituted with 1 or 2 substituents independently selected from F, -OH, -OCH3, -OCF2H, -OCD3, -CH3, -CH2CH3, -CH2OCH3, -CH2OCH2F, -CH2OCHF2, - CH2OCF3, -OCF3, -OCH2CH3, and CN, (i) a 6-7 membered fused bicyclic ring optionally substituted with 1 or 2 substituents independently selected from F and -CH3, (i¡) a 6-bridged ring -7 members and (iv) a 6-8 membered spirocyclic ring; and hetCyc2 is a saturated 5-6 membered monocyclic heterocyclic ring having 1 or 2 ring heteroatoms independently selected from N and O; as long as the compound is not: N-(2-chloro-3-((3,5-dimethyl-4-oxo-3,4-dihydroquinazolin-6-yl)amino)-4-fluorophenyl)pyrrolidine-lsulfonamide, (R )-N-(2-chloro-3-((3,5-dimethyl-4-oxo-3,4-dihydroquinazolin-6-¡l)amino)-4-fluorophen¡l)-3fluoropyrrolidin-l- sulfonamide, or N-(2-chloro-3-((3,5-dimethyl-4-oxo-3,4-dihydroquinazolin-6-l)amino)-4-fluorophenyl )-N-ethyl-Nmethylamino-l-sulfonamide. In one embodiment, a compound of Formula I-A iviA / a / zuzz / u 1 o / u j is provided herein. or a pharmaceutically acceptable salt thereof, wherein: L is NH or O; R1 is C1-C6 alkyl, C1-C6 deuteroalkyl, C1-C6 fluoroalkyl, C3-C6 cycloalkyl, (C3-C6 cycloalkyl)CH2-, (C1-C6 alkoxy)Cl-C6 alkyl-, Ar1, AóCFb-, hetAr1 or hetCyc1; Ar1 is phenyl which is optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from halogen and C1-C3 alkyl; hetAr1 is a 5-6 membered heteroaryl ring having 1 or 2 ring nitrogen atoms and which is optionally substituted with 1, 2 or 3 substituents independently selected from halogen and C1-C3 alkyl; hetCyc1 is a saturated 4-6 membered monocyclic heterocyclic ring having one ring oxygen atom; R2is -CH3, -CH2CH3, -CH=CH2, F, Cl, Br or CN; R3is F or Cl; R4is H or F; R5 is H, F or Cl; R6is C1-C6 alkyl, and R7is C1-C6 alkyl, hetCyc2o C3-C6 cycloalkyl, or R6and R7 together with the nitrogen atom to which they are attached form a saturated ring system selected from (i) a 4-6 membered monocyclic ring optionally having a second heteroatom of ring that is O, wherein said ring is optionally substituted with 1 or 2 substituents independently selected from F, -OH, -OCH3, -OCF2H, -OCD3, -CH3 and -CH2CH3, (ii) a fused bicyclic ring of 6- 7 membered optionally substituted with 1 or 2 substituents independently selected from F and -CFh, (iii) a 6-7 membered bridged ring and (iv) a 7 membered spirocyclic ring; and hetCyc2 is a saturated 5-6 membered monocyclic heterocyclic ring having 1 or 2 ring heteroatoms independently selected from N and O; as long as the compound is not: N-(2-chloro-3-((3,5-dimethyl-4-oxo-3,4-dihydroquinazolin-6-íl)amino)-4-fluorophenyl)pyrrolidin-lsulfonamide, (R) -N-(2-chloro-3-((3,5-dimethyl-4-oxo-3,4-dihydroquinazolin-6-¡l)amino)-4-fluorophenyl)-3fluoropyrrolidin-l-sulfonamide, or N-(2-chloro-3-((3,5-dimethyl-4-oxo-3,4-dihydroquinazolin-6-l)amino)-4-fluorophen l)-N-ethyl-Nmethylamino-l-sulfonamide. For the complex chemical names used herein, a substituent group is typically named before the group to which it is attached. For example, methoxyethyl comprises an ethyl backbone with a methoxy substituent. The term halogen means -F (sometimes referred to herein as fluoro or fluoros), Cl, -Br and -I. As used herein, the terms C1-C3 alkyl and C1-C6 alkyl refer to straight-chain or branched-chain saturated monovalent hydrocarbon radicals of one to three or one to six carbon atoms, respectively. Examples of alkyl groups include, but are not limited to, methyl, ethyl, 1-propyl, isopropyl, 1-butyl, isobutyl, sec-butyl, tert-butyl, 2-methyl-2-propyl, pentyl, neopentyl, and hexyl. As used herein, the term C1-C6 fluoroalkyl refers to a C1-C6 alkyl radical as defined herein, wherein one to three hydrogen atoms are replaced with one to three fluorine atoms, respectively. . Examples include, but are not limited to, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl and 2,2,2-trifluoroethyl. As used herein, the term C1-C6 deuteroalkyl refers to a ClC6 alkyl radical as defined herein, which is substituted with one to six deuterium atoms. An example includes, but is not limited to, -CD3. The term C3-C6 cycloalkyl means a saturated carbocyclic ring having 3 to 6 ring carbon atoms, for example, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. As used herein, the term C1-C6 alkoxy refers to straight or branched chain saturated monovalent alkoxy radicals of one to six carbon atoms, wherein the radical is on the oxygen atom. Examples of alkoxy groups include methoxy, ethoxy, propoxy and isopropoxy. As used herein, the term (C1-C6 alkoxy)Cl-C6 alkyl refers to a C1-C6 alkyl radical as defined herein, wherein one of the carbon atoms is substituted with a C1 group. -C6 alkoxy. Examples of (C1-C6 alkoxy)Cl-C6 alkyl groups include methoxymethyl (CH3OCH2-) and methoxyethyl (CH3OCH2CH2-). The term heteroaryl, as used herein, refers to an aromatic molecule that contains at least one heteroatom as part of the aromatic ring. The term heterocycle, as used herein, refers to a saturated cycloalkyl group in which one or more of the methylene groups of the ring (-CH2-) have been replaced by a heteroatom. For example, the term hetCyc1, as used herein, refers to a saturated 4-6 membered monocyclic cycloalkyl ring in which one of the methylene groups has been replaced with -O-, and the term hetCyc2, as As used herein, it refers to a saturated 5-6 membered monocyclic cycloalkyl ring in which one or two of the methylene groups have been replaced with a group independently selected from -O- and -N-, provided that the ring does not contain two adjacent ring heteroatoms. Throughout the disclosure, it will be understood that the amount and nature of optional substituent groups will be limited to the extent that such substitutions make chemical sense. The term compound, as used herein, is intended to include all stereoisomers, geometric isomers, tautomers and isotopes of the structures represented. Compounds herein identified by name or structure as a particular tautomeric form are intended to include other tautomeric forms unless otherwise specified. In one embodiment of Formula I, L is NH. In one embodiment of Formula I, L is O. In one embodiment of Formula I, R1 is C1-C6 alkyl. Non-limiting examples include methyl, ethyl and isopropyl. In one embodiment of Formula I, R1 is methyl. In one embodiment of Formula I, R1 is C1-C6 deuteroalkyl. A non-limiting example includes -CD3. In one embodiment of Formula I, R1 is C1-C6 fluoroalkyl. In one embodiment of Formula I, R1 is fluoromethyl. In one embodiment of Formula I, R1 is C3-C6 cycloalkyl. Non-limiting examples include cyclopropyl, cyclobutyl and cyclopentyl. In one embodiment of Formula I, R1 is (C3-C6 cycloalkyl)CH2-. A non-limiting example includes cyclopropylmethyl. In one embodiment of Formula I, R1 is (C1-C6 alkoxy)Cl-C6 alkyl-. A non-limiting example includes methoxyethyl. In one embodiment of Formula I, R1 is Ar1. In one embodiment, Ar1 is phenyl which is optionally substituted with 1, 2 or 3 substituents independently selected from halogen and C1-C3 alkyl. A non-limiting example of Ar1 is phenyl. In one embodiment of Formula I, R1 is Ar'CHz-, In one embodiment, the Ar1 moiety is optionally substituted with 1 or 2 substituents independently selected from halogen and C1-C3 alkyl. A non-limiting example of Ar1CH2- is bencllo (-CHzCeHs). In one embodiment of Formula I, R1 is hetAr1. In one embodiment, hetAr1 is a 5-6 membered heteroaryl ring having 1 or 2 ring nitrogen atoms and which is optionally substituted with 1 or 2 substituents independently selected from halogen and C1-C3 alkyl. In one embodiment, hetAr1 is not substituted. A non-limiting example is pyridyl. In one embodiment of Formula I, R1 is hetCyc1. A non-limiting example includes tetrahydrofuranyl. IVIA / a / ZUZZ / U I O / U J In one embodiment of Formula I, R2 is -ch3. In one embodiment of Formula I, R2 is -CH2CH3. In one embodiment of Formula I, R2 is -ch=ch2. In one embodiment of Formula I, R2 is F. In one embodiment of Formula I, R2 is Cl. In one embodiment of Formula I, R2 is Br. In one embodiment of Formula I, R2 is CN. In one embodiment of Formula I, R2 is -CH3, F 0 Cl. In one embodiment of Formula I, R2 is FoCI. In one embodiment of Formula I, R3 is F. In one embodiment of Formula I, R3 is Cl. In one embodiment of Formula I, R4 is H. In one embodiment of Formula I, R4 is F. In one embodiment of Formula I, R5 is H. In one embodiment of Formula I, R5 is F. In one embodiment of Formula I, R5 is Cl. In one embodiment embodiment of Formula I, R6 is C1-C6 alkyl and R7 is C1-C6 alkyl, hetCyc2 or C3-C6 cycloalkyl. In one embodiment of Formula I, R6 is methyl or ethyl. In one embodiment of Formula I, R7 is C1-C6 alkyl. In one embodiment, R7 is methyl. In one embodiment of Formula I, R7 is hetCyc2. In one embodiment, R7 is tetrahydrofuranyl. In one embodiment of Formula II, R7 is C3-C6 cycloalkyl. In one embodiment, R7 is cyclopropyl or cyclobutyl. In one embodiment of Formula I, R6 is methyl or ethyl and R7 is methyl, tetrahydrofuranyl, cyclopropyl or cyclobutyl. In one embodiment of Formula I, R6 and R7 together with the nitrogen atom to which they are attached form a saturated ring system selected from (i) a 4-6 membered monocyclic ring optionally having a second ring heteroatom that is Or, wherein said ring is optionally substituted with 1 or 2 substituents independently selected from F, -OH, OCH3, -OCHF2, -OCD3, -CH3 and -CH2CH3, (ii) an optionally substituted 6-7 membered fused bicyclic ring with 1 or 2 substituents independently selected from F and -CH3, (ii) a 6-7 membered bridged ring and (iv) a 6-8 membered spirocyclic ring. In one embodiment of Formula I, R6 and R7 together with the nitrogen atom to which they are attached form a 4-6 membered monocyclic ring optionally having a second ring heteroatom which is O, wherein said ring is optionally substituted with 1 or 2 substituents independently selected from F, -OH, -OCH3, -OCF2H, -OCD3, -CH3, -CH2CH3, CH2OCH3, -CH2OCH2F, -CH2OCHF2, -CH2OCF3, -OCF3, -OCH2CH3, and CN. Non-limiting examples include the structures: In one embodiment of Formula I, R6 and R7 together with the nitrogen atom to which they are attached form a 4-6 membered monocyclic ring, wherein said ring is optionally substituted with a substituent selected from F, -OH, -OCH3 , -OCHF2, -OCD3, -CH3, -CH2CH3, CH2OCH3, -CH2OCH2F, -CH2OCHF2, -CH2OCF3, -OCF3, -OCH2CH3, and CN. In one embodiment of Formula I, R6 and R7 together with the nitrogen atom to which they are attached form a 4-6 membered saturated monocyclic ring substituted with F. Examples include the structures: । An^F Q, \___ / F In one embodiment of Formula I, R6 and R7 together with the nitrogen atom to which they are attached form a 6-7 membered fused bicyclic ring optionally substituted with 1 or 2 substituents independently selected from F and -CH3. Non-limiting examples include the structures: In one embodiment of Formula I, R6 and R7 together with the nitrogen atom to which they are attached form a 6-7 membered bridged ring. Non-limiting examples include the structures: ινΐΛ / a / zuzz / u 1 o / u j In one embodiment of Formula I, R6 and R7 together with the nitrogen atom to which they are attached form a 6-8 membered spirocyclic ring. A non-limiting example includes the structure: Any of the above-mentioned embodiments of Formula I can be combined with each other. In one embodiment, a compound of Formula II is provided herein. or a pharmaceutically acceptable salt thereof, wherein: L is NH or O; R1 is C1-C6 alkyl or C1-C6 fluoroalkyl; R2is -CH3, -CH2CH3, -CH=CH2, F, Cl, Br or CN; R3is F or Cl; R4is H or F; R5 is H, F or Cl; R6is C1-C6 alkyl, and R7is C1-C6 alkyl, hetCyc2o C3-C6 cycloalkyl, or R6and R7 together with the nitrogen atom to which they are attached form a saturated ring system selected from (i) a 4-6 membered monocyclic ring optionally having a second heteroatom of ring which is O, wherein said ring is optionally substituted with 1 or 2 substituents independently selected from F, -OH, -OCH3, -OCHF2, -OCD3, -CH3, -CH2CH3, -CH2OCH3, -CH2OCH2F, -CH2OCHF2, - CH2OCF3, -OCF3, -OCH2CH3, and CN, (i) a 6-7 membered fused bicyclic ring optionally substituted with 1 or 2 substituents independently selected from F and -CH3, (iii) a 6-7 bridged ring members and (iv) a 6-8 membered spirocyclic ring; and hetCyc2 is a saturated 5-6 membered monocyclic heterocyclic ring having 1 or 2 ring heteroatoms independently selected from N and O; provided the compound is not: N-(2-chloro-3-((3,5-dimethyl-4-oxo-3,4-dihydroquinazolin-6yl)amino)-4-fluorophenyl)pyrrolídin-l -sulfonamide, (R)-N-(2-chloro-3-((3,5-dimethyl-4-oxo-3,4-dihydroquinazolin-6-yl)amino)-4-fluorophen ¡l)-3fluoropyrrolidin-l-sulfonamide, or N-(2-chloro-3-((3,5-dimethyl-4-oxo-3,4-dihydroquinazolin-6-l)amino)-4-fluorophenyl )-N-ethyl-Nmethylamino-l-sulfonamide. In one embodiment of Formula II, L is NH. In one embodiment of Formula II, L is O. In one embodiment of Formula II, R1 is C1-C6 alkyl. Non-limiting examples include methyl, ethyl and isopropyl. In one embodiment of Formula II, R1 is methyl. In one embodiment of Formula II, R1 is C1-C6 fluoroalkyl. In one embodiment of Formula II, R1 is fluoromethyl. In one embodiment of Formula II, R2 is -CH3. In one embodiment of Formula II, R2 is -CH2CH3. In one embodiment of Formula II, R2 is -CH=CH2. In one embodiment of Formula II, R2 is F. In one embodiment of Formula II, R2 is CL In one embodiment of Formula II, R2 is Br. In one embodiment of Formula II, R2 is CN. In one embodiment of Formula II, R2 is -CH3, F or CL In one embodiment of Formula II, R2 is F or Cl. In one embodiment of Formula II, R3 is F. In one embodiment of Formula II, R3 is CL In one embodiment of Formula II, R4 is H. In one embodiment of Formula II, R4 is F. In one embodiment of Formula II, R5 is H. In one embodiment of Formula II, R5 is F. In one embodiment of Formula II, R5 is Cl. In one embodiment of Formula II, R6 is C1-C6 alkyl and R7 is C1-C6 alkyl, hetCyc2 or C3-C6 cycloalkyl. In one embodiment of Formula II, R6 is methyl or ethyl. In one embodiment of Formula II, R7 is C1-C6 alkyl. In one embodiment, R7 is methyl. In one embodiment of Formula II, R7 is hetCyc2. In one embodiment, R7 is tetrahydrofuranyl. In one embodiment of Formula II, R7 is C3-C6 cycloalkyl. In one embodiment, R7 is cyclopropyl or cyclobutyl. In one embodiment of Formula II, R6 is methyl or ethyl and R7 is methyl, tetrahydrofuranyl, cyclopropyl or cyclobutyl. In one embodiment of Formula II, R6 and R7 together with the nitrogen atom to which they are attached form a saturated ring system selected from (i) a 4-6 membered monocyclic ring optionally having a second ring heteroatom that is Or, wherein said ring is optionally substituted with 1 or 2 substituents independently selected from F, -OH, OCH3, -OCHF2, -OCD3, -CH3 and -CH2CH3, (ii) an optionally substituted 6-7 membered fused bicyclic ring with 1 or 2 substituents independently selected from F and -CH3, (i¡) a 6-7 membered bridged ring and (iv) a 6-8 membered spirocyclic ring. In one embodiment of Formula II, R6 and R7 together with the nitrogen atom to which they are attached form a 4-6 membered monocyclic ring optionally having a second ring heteroatom which is O, wherein said ring is optionally substituted with 1 or 2 substituents independently selected from F, -OH, -OCH3, -OCF2H, -OCD3, -CH3, -CH2CH3, CH2OCH3, -CH2OCH2F, -CH2OCHF2, -CH2OCF3, -OCF3, -OCH2CH3, and CN. Non-limiting examples include the structures: In one embodiment of Formula II, R6 and R7 together with the nitrogen atom to which they are attached form a saturated 4-6 membered monocyclic ring optionally substituted with F. Examples include the structures: F In one embodiment of Formula II, R6 and R7 together with the nitrogen atom to which they are attached form a 6-7 membered fused bicyclic ring optionally substituted with 1 or 2 substituents independently selected from F and -CH3. Non-limiting examples include the structures: In one embodiment of Formula II, R6 and R7 together with the nitrogen atom to which they are attached form a 6-7 membered bridged ring. Non-limiting examples include the structures: In one embodiment of Formula II, R6 and R7 together with the nitrogen atom to which they are attached form a 6-8 membered spirocyclic ring. A non-limiting example includes the structure: ινΐΛ / a / zuzz / u 1 o 1 u d Any of the above-mentioned embodiments of Formula II can be combined with each other. In one embodiment, a compound of Formula III is provided herein: or a pharmaceutically acceptable salt thereof, wherein: L is NH or O; R1 is C1-C6 alkyl, C1-C6 deuteroalkyl, C1-C6 fluoroalkyl, C3-C6 cycloalkyl, (C3-C6 cycloalkyl)CH2-, (C1-C6 alkoxy)Cl-C6 alkyl-, Ar1, ΑΝΟΗς-, hetAr1 or hetCyc1; Ar1 is phenyl which is optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from halogen and C1-C3 alkyl; hetAr1 is a 5-6 membered heteroaryl ring having 1 or 2 ring nitrogen atoms and which is optionally substituted with 1, 2 or 3 substituents independently selected from halogen and C1-C3 alkyl; hetCyc1 is a saturated 4-6 membered monocyclic heterocyclic ring having one ring oxygen atom; R2is -CH2CH3, -CH=CH2, F, CI, Br or CN; R3is F or CI; R4is H or F; R5is H, F or CI; R6is C1-C6 alkyl, and R7is C1-C6 alkyl, hetCyc2o C3-C6 cycloalkyl, or R6and R7 together with the nitrogen atom to which they are attached form a saturated ring system selected from (i) a 4-6 membered monocyclic ring optionally having a second heteroatom of ring that is O, wherein said ring is optionally substituted with 1 or 2 substituents independently selected from F, -OH, -OCH3, -OCHF2, -OCD3, -CH3, -CH2CH3, -CH2OCH3 / -CH2OCH2F, -CH2OCHF2, -CH2OCF3, -OCF3, -OCH2CH3, and CN, (ii) a 6-7 membered fused bicyclic ring optionally substituted with 1 or 2 substituents independently selected from F and -CH3, (iii ) a 6-7 membered bridging ring and (iv) a 6-8 membered spirocyclic ring; and hetCyc2 is a saturated 5-6 membered monocyclic heterocyclic ring having 1 or 2 ring heteroatoms independently selected from N and O. In one embodiment of Formula III, L is NH. In one embodiment of Formula III, L is O. In one embodiment of Formula III, R1 is C1-C6 alkyl or C1-C6 fluoroalkyl. In one embodiment of Formula III, R1 is C1-C6 alkyl. Non-limiting examples include methyl, ethyl and isopropyl. In one embodiment of Formula III, R1 is methyl. In one embodiment of Formula III, R1 is C1-C6 fluoroalkyl. In one embodiment of Formula III, R1 is fluoromethyl. In one embodiment of Formula III, R2 is -CH=CH2. In an embodiment of Formula III, R2 is F. In an embodiment of Formula III, R2 is Cl. In an embodiment of Formula III, R2 is Br. In an embodiment of Formula III, R2 is CN. In an embodiment of Formula III, R2 is F 0 CL. In an embodiment of Formula III, R3 is F. In an embodiment of Formula III, R3 is Cl. In an embodiment of Formula III, R3 is Cl. Formula III, R4 is H. In an embodiment of Formula III, R4 is F. In an embodiment of Formula III, R5 is H. In an embodiment of Formula III, R5 is F. In one embodiment of Formula III, R5 is CL In one embodiment of Formula III, R6 is C1-C6 alkyl and R7 is C1-C6 alkyl, hetCyc2o C3-C6 cycloalkyl. In one embodiment of Formula III, R6 is methyl or ethyl. In one embodiment of Formula III, R7 is C1-C6 alkyl. In one embodiment, R7 is methyl. In one embodiment of Formula III, R7 is hetCyc2. In one embodiment, R7 is tetrahydrofuranyl. In one embodiment of Formula III, R7 is C3-C6 cycloalkyl. In one embodiment, R7 is cyclopropyl or cyclobutyl. In one embodiment of Formula III, R6 is methyl or ethyl and R7 is methyl, tetrahydrofuranyl, cyclopropyl or cyclobutyl. In one embodiment of Formula III, R6 and R7 together with the nitrogen atom to which they are attached form a saturated ring system selected from (i) a 4-6 membered monocyclic ring optionally having a second ring heteroatom that is Or, wherein said ring is optionally substituted with 1 or 2 substituents independently selected from F, -OH, OCH3, -OCHF2, -OCD3, -CH3 and -CH2CH3, (i) an optionally substituted 6-7 membered fused bicyclic ring with 1 or 2 substituents independently selected from F and -CH3, (iii) a 6-7 membered bridged ring and (iv) a 6-8 membered spirocyclic ring. In one embodiment of Formula III, R6 and R7 together with the nitrogen atom to which they are attached form a 4-6 membered monocyclic ring optionally having a second ring heteroatom which is O, wherein said ring is optionally substituted with 1 or 2 substituents independently selected from F, -OH, -OCH3, -OCF2H, -OCD3, -CH3, -CH2CH3, CH2OCH3, -CH2OCH2F, -CH2OCHF2, -CH2OCF3, -OCF3, -OCH2CH3, and CN. Non-limiting examples include the structures: F C.N. Οχ CF3 ^CHF2O OCF3 In one embodiment of Formula III, R6 and R7 together with the nitrogen atom to which they are attached form a saturated 4-6 membered monocyclic ring optionally substituted with F. Examples include the structures: F In one embodiment of Formula III, R6 and R7 together with the nitrogen atom to which they are attached form a 6-7 membered fused bicyclic ring optionally substituted with 1 or 2 substituents independently selected from F and -CH3. Non-limiting examples include the structures: In one embodiment of Formula III, R6 and R7 together with the nitrogen atom to which they are attached form a 6-7 membered bridged ring. Non-limiting examples include the structures: In one embodiment of Formula III, R6 and R7 together with the nitrogen atom to which they are attached form a 6-8 membered spirocyclic ring. A non-limiting example includes the structure: Any of the above-mentioned embodiments of Formula III can be combined with each other. In one embodiment, a compound of Formula IV is provided herein. or a pharmaceutically acceptable salt thereof, wherein: L is NH or O; R1is C1-C6 alkyl, C1-C6 deuteroalkyl, C1-C6 fluoroalkyl, C3-C6 cycloalkyl, (C3-C6 cycloalkyl)CH2-, (C1-C6 alkoxy)Cl-C6 alkyl-, Ar1, AECH?-, hetAr1or hetCyc1 ; Ar1 is phenyl which is optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from halogen and C1-C3 alkyl; hetAr1 is a 5-6 membered heteroaryl ring having 1 or 2 ring nitrogen atoms and which is optionally substituted with 1, 2 or 3 substituents independently selected from halogen and C1-C3 alkyl; hetCyc1 is a saturated 4-6 membered monocyclic heterocyclic ring having one ring oxygen atom; R2is -CH3, -CH2CH3, -CH=CH2, F, Cl, Br or CN; R3is F or Cl; R4is H or F; R5 is H, F or Cl; R6is C1-C6 alkyl, and R7is C1-C6 alkyl, hetCyc2o C3-C6 cycloalkyl, or R6and R7 together with the nitrogen atom to which they are attached form a saturated ring system selected from (i) a 4-6 membered monocyclic ring optionally having a second heteroatom of ring which is O, wherein said ring is optionally substituted with 1 or 2 substituents independently selected from F, -OH, -OCH3, -OCHF2, -OCD3, -CH3, -CH2CH3, -CH2OCH3, -CH2OCH2F, -CH2OCHF2, - CH2OCF3, -OCF3, -OCH2CH3, and CN, (i) a 6-7 membered fused bicyclic ring optionally substituted with 1 or 2 substituents independently selected from F and -CH3, (i¡) a 6-bridged ring -7 members and (iv) a 6-8 membered spirocyclic ring; and hetCyc2 is a saturated 5-6 membered monocyclic heterocyclic ring having 1 or 2 ring heteroatoms independently selected from N and O; where when R1 is methyl, L is NH, R3 is Cl, R4 is F, R5 is H, and R5 is methyl and R7 is ethyl, or R6 and R7 together with the nitrogen atom to which they are attached form a pyrrolidinyl or 3fluoropyrrolidinyl, then R2 is -CH2CH3, - CH=CH2, F, Cl, Br or CN. In one embodiment of Formula IV, L is NH. In one embodiment of Formula IV, L is O. In one embodiment of Formula IV, R1 is C1-C6 alkyl or C1-C6 fluoroalkyl. In one embodiment of Formula IV, R1 is C1-C6 alkyl. Non-limiting examples include methyl, ethyl and isopropyl, provided that when R1 is methyl, L is NH, R3 is Cl, R4 is F, R5 is H, and R6 is methyl and R7 is ethyl, or R6 and R7 together with the nitrogen atom to which they are attached form a pyrrolidinyl or 3-fluoropyrrolidinyl, then R2 is -CH2CH3, -CH=CH2, F, Cl, Br or CN. In one embodiment of Formula IV, R1 is methyl. In one embodiment of Formula IV, R1 is C1-C6 fluoroalkyl. In one embodiment of Formula IV, R1 is fluoromethyl. In one embodiment of Formula IV, R2 is -CH3. In one embodiment of Formula IV, R2 is -CH2CH3. In one embodiment of Formula IV, R2 is -CH=CH2. In one embodiment of Formula IV, R2 is F. In one embodiment of Formula IV, R2 is Cl. In one embodiment of Formula IV, R2 is Br. In one embodiment of Formula IV, R2 is CN. In one embodiment of Formula IV, R2 is -CH3, F 0 CL In one embodiment of Formula IV, R2 is F 0 CL In one embodiment of Formula IV, R3 is F. In one embodiment In one embodiment of Formula IV, R3 is Cl. In one embodiment of Formula IV, R4 is H. In one embodiment of Formula IV, R4 is F. In one embodiment of Formula IV, R5 is H. In one embodiment of Formula IV, R5 is F. In one embodiment of Formula IV, R5 is Cl. In one embodiment of Formula IV, R6 is C1-C6 alkyl and R7 is C1-C6 alkyl, hetCyc2o C3-C6 cycloalkyl. In one embodiment of Formula IV, R6 is methyl or ethyl. In one embodiment of Formula IV, R7 is C1-C6 alkyl. In one embodiment, R7 is methyl. In one embodiment of Formula IV, R7 is hetCyc2. In one embodiment, R7 is tetrahydrofuranyl. In one embodiment of Formula IV, R7 is C3-C6 cycloalkyl. In one embodiment, R7 is cyclopropyl or cyclobutyl. In one embodiment of Formula IV, R6 is methyl or ethyl and R7 is methyl, tetrahydrofuranyl, cyclopropyl or cyclobutyl. In one embodiment of Formula IV, R6 and R7 together with the nitrogen atom to which they are attached form a saturated ring system selected from (i) a 4-6 membered monocyclic ring optionally having a second ring heteroatom that is O, wherein said ring is optionally substituted with 1 or 2 substituents independently selected from F, -OH, OCH3, -OCHF2, -OCD3, -CH3, -CH2CH3, -CH2OCH3, -CH2OCH2F, -CH2OCHF2, -CH2OCF3, -OCF3 , -OCH2CH3 and CN, (i¡) a 6-7 membered fused bicyclic ring optionally substituted with 1 or 2 substituents independently selected from F and -CH3, (iii) a 6-7 member bridged ring and (iv) a 6-8 membered spirocyclic ring. In one embodiment of Formula IV, R6 and R7 together with the nitrogen atom to which they are attached form a 4-6 membered monocyclic ring optionally having a second ring heteroatom which is O, wherein said ring is optionally substituted with 1 or 2 substituents independently selected from F, -OH, -OCH3, -OCF2H, -OCD3, -CH3, -CH2CH3, CH2OCH3, -CH2OCH2F, -CH2OCHF2, -CH2OCF3, -OCF3, -OCH2CH3, and CN. Non-limiting examples include the structures: In one embodiment of Formula IV, R6 and R7 together with the nitrogen atom to which they are attached form a saturated 4-6 membered monocyclic ring optionally substituted with F. Examples include the structures: In one embodiment of Formula IV, R6 and R7 together with the nitrogen atom to which they are attached form a 6-7 membered fused bicyclic ring optionally substituted with 1 or 2 substituents independently selected from F and -CH3. Non-limiting examples include the structures: In one embodiment of Formula IV, R6 and R7 together with the nitrogen atom to which they are attached form a 6-7 membered bridged ring. Non-limiting examples include the structures: ΜΛ / a / ZUZZ / U 1 0 / U J In one embodiment of Formula IV, R6 and R7 together with the nitrogen atom to which they are attached form a 6-8 membered spirocyclic ring. A non-limiting example includes the structure: Any of the above-mentioned embodiments of Formula IV can be combined with each other. In one embodiment, a compound of Formula V is provided herein. or a pharmaceutically acceptable salt thereof, wherein: L is NH; R1 is C1-C6 alkyl; R2is F or Cl; R3es Cl; R4is F; R5is H; R6 and R7 together with the nitrogen atom to which they are attached form a saturated ring system selected from (i) a 4-6 membered monocyclic ring optionally having a second ring heteroatom which is O, wherein said ring is optionally substituted with 1 or 2 substituents independently selected from F, -OH, -OCH3, -OCHF2, -OCD3, -CH3, CH2CH3, -CH2OCH3, -CH2OCH2F, -CH2OCHF2, -CH2OCF3, -OCF3, -OCH2CH3 and CN, and (ii ) a 6-7-membered bridging ring. In one embodiment of Formula V, R6 and R7 together with the nitrogen atom to which they are attached form a saturated 4-6 membered monocyclic ring optionally having a second ring heteroatom which is O, wherein said ring is optionally substituted. with 1 or 2 substituents independently selected from F, -OH, -OCH3, -OCHF2, -OCD3, -CH3, 34 CH2CH3, -CH2OCH3, -CH2OCH2F, -CH2OCHF2, -CH2OCF3, -OCF3, -OCH2CH3, and CN. In one embodiment of Formula V, R6 and R7 together with the nitrogen atom to which they are attached form a saturated 4-6 membered monocyclic ring, wherein said ring is optionally substituted with 1 or 2 substituents selected independently from F. In one embodiment of Formula V, R6 and R7 together with the nitrogen atom to which they are attached form a saturated 6-7 membered bridged ring. In one embodiment of Formula V, R1 is methyl. In one embodiment of Formula V, R3 is F. In one embodiment of Formula V, R3 is Cl. In one embodiment of Formula V, R1 is methyl, R3 is F, and R6 and R7 together with the nitrogen atom to which they are attached form a saturated 4-6 membered monocyclic ring, wherein said ring is optionally substituted with 1 or 2 substituents selected independently of F. In one embodiment, said ring is substituted with an F. In one embodiment of Formula V, R1 is methyl, R3 is chloro, and R6 and R7 together with the nitrogen atom to which they are attached form a saturated 6-7 membered bridged ring. The compounds of Formula I, Formula I-A, Formula II, Formula III, Formula IV and Formula V include pharmaceutically acceptable salts thereof. Furthermore, the compounds of Formula I also include other salts of said compounds that are not necessarily pharmaceutically acceptable salts and that may be useful as intermediates for preparing and / or purifying compounds of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V and / or to separate enantiomers of compounds of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V. The term "pharmaceutically acceptable salt" refers to a conventional acid addition or basic addition salt that retains the biological efficacy and properties of the compounds of Formula (I) and that can be formed with organic or inorganic bases or suitable non-toxic organic or inorganic acids. Examples of acid addition salts include salts derived from inorganic acids, such as, among others, hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, sulfamic acid, phosphoric acid, nitric acid and perchloric acid and derived from various organic acids, such as, but not limited to, acetic acid, propionic acid, benzoic acid, glycolic acid, phenylacetic acid, salicylic acid, malonic acid, maleic acid, oleic acid, pamoic acid, palmitic acid, benzenesulfonic acid, toluenesulfonic acid, methanesulfonic acid, oxalic acid , tartaric acid, succinic acid, citric acid, malic acid, lactic acid, glutamic acid, fumaric acid and the like. Examples of basic addition salts are salts derived from ammonium, potassium, sodium and quaternary ammonium hydroxides, such as tetramethylammonium hydroxide. These salts often exhibit more favorable solubility properties than the compounds used for their iviA / a / zuzz / u 1 o / u j preparation and are therefore more suitable for use in the preparation of various pharmaceutical formulations. It will be further appreciated that the compounds of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V or their salts may be isolated in the form of solvates and, accordingly, any such solvate is included within the scope of the present invention. For example, the compounds of Formula I and salts thereof may exist in unsolvated forms as well as solvated with pharmaceutically acceptable solvents such as water, ethanol and the like. The term solvate refers to non-covalent stoichiometric or non-stoichiometric combinations of solvent and solute. The term hydrate refers to non-covalent stoichiometric or non-stoichiometric combinations of water and solute. For example, compounds of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt or polymorph thereof, may exist in unsolvated as well as solvated forms. pharmaceutically acceptable solvents such as anisole, dichloromethane, toluene, 1,4-dioxane, water and the like. The compounds provided herein may contain one or more centers of asymmetry and, therefore, may be prepared and isolated in a mixture of isomers, such as a racemic mixture, or in an enantiomerically pure form. The present invention includes all stereoisomers and individual geometric isomers of the compounds of the present invention and mixtures thereof. Individual enantiomers can be obtained by chiral separation or by use of the relevant enantiomer in the synthesis. Bonds to a carbon atom of the compounds of the invention can be represented herein by using a solid line (-------), a thick straight bar (—), a dashed straight bar (. .....), a solid wedge (—) or a dashed wedge (........). The use of a solid line to represent bonds with asymmetric carbon atoms is intended to indicate that all possible stereoisomers (e.g., specific enantiomers, racemic mixtures, etc.) on that carbon atom are included. The use of a thick straight bar or a dashed straight bar is to indicate relative stereochemistry. The use of a solid wedge or a dashed wedge is to indicate absolute stereochemistry. For compounds disclosed in the examples comprising one or more stereocenters, if specific stereochemistry is not shown, the compound is intended to include a mixture of stereoisomers. As used herein, the term stereocenter refers to an atom with three or more different bonds, where the exchange of two of these bonds leads to another stereoisomer. Examples include, but are not limited to, an sp3(tetrahedral) carbon atom that has four different bonds. The compounds of Formula I, Formula I-A, Formula II and Formula III can exist in various geometric isomeric forms. In addition, certain compounds of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V may contain one or more asymmetric centers, so they exist in stereoisomeric and diastereomeric forms. The term stereoisomer denotes a compound that has identical molecular connectivity and multiplicity of bonds, but that differs in the arrangement of its atoms in space. All these compounds, such as cis isomers, trans isomers, diastereomeric mixtures, racemates, non-racemic mixtures of enantiomers, substantially pure and pure enantiomers are within the scope of the invention. In one embodiment, the substantially pure enantiomers contain up to 5% by weight of the corresponding opposite enantiomer. In one embodiment, the substantially pure enantiomers contain up to 2% by weight of the corresponding opposite enantiomer. In one embodiment, the substantially pure enantiomers contain up to 1% by weight of the corresponding opposite enantiomer. Optical isomers can be prepared by resolving racemic mixtures by known methods, for example, by using an optically active acid or base to form diastereoisomeric salts or by forming covalent diastereomers. Suitable acids include, for example, tartaric acid, diacetyltartaric acid, dibenzoyltartaric acid, ditoluoyltartaric acid and camphorsulfonic acid. Diastereoisomeric mixtures can be separated into individual diastereoisomers based on their physical and / or chemical differences, by methods known to those in the mid-level trade, such as chromatography or fractional crystallization. Subsequently, the optically active bases or acids are released from the separated diastereoisomeric salts. Various optical isomer separation methods include chiral chromatography (e.g. chiral HPLC columns) optionally used by derivatization with the aim of maximizing enantiomer separation. Suitable chiral HPLC columns are Diacel columns, such as CHIRALPAK or CHIRALCEL columns, which can be routinely chosen as desired. Where appropriate, enzymatic separations carried out by derivatization can also be used. Optically active compounds of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V can also be prepared by using optically active starting materials with chiral synthesis without racemization reaction conditions. Also included are acid addition salts or basic addition salts, where the counterion is optically active, for example, d-lactate or I-lysine, or racemic, for example, dl-tartrate or dl-arginine. When any racemate crystallizes, two different types of crystals are possible. The first type is the racemic compound (true racemate) mentioned above, where a homogeneous crystal form containing both enantiomers in equimolar amounts is produced. The second type is the racemic mixture or conglomerate, where two are produced with an alkaline reagent and subsequently convert the free base to a pharmaceutically acceptable acid addition salt. Acid addition salts of the basic compounds of this invention can be prepared by treating the basic compound with a substantially equivalent amount of the selected organic or mineral acid in an aqueous solvent medium or in a suitable organic solvent, such as methanol or ethanol. After evaporation of the solvent, the desired solid salt is obtained. The desired acid salt can also be precipitated from a solution of the free base in an organic solvent by adding a suitable mineral or organic acid to the solution. The acids that can be used to prepare pharmaceutically acceptable acid addition salts of those basic compounds are those that form non-toxic acid addition salts, that is, salts containing pharmacologically acceptable anions, such as as hydrochloride salts, hydrobromide, hydroiodine, nitrate, sulfate, bisulfate, phosphate, acid phosphate, isonicotinate, acetate, lactate, salicylate, citrate, acid citrate, tartrate, pantothenate, bitartrate, ascorbate, succinate, maleate, gentisinate, fumarate, gluconate , glucuronate, saccharate, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzenesulfonate, ptoluenesulfonate and pamoate. Examples of salts include, but are not limited to, salts of acetate, acrylate, benzenesulfonate, benzoate (such as chlorobenzoate, methyl benzoate, dinitrobenzoate, hydroxybenzoate and methoxy benzoate), bicarbonate, bisulfate, bisulfite, bitartrate, borate, bromide, butyn1,4 -dioate, calcium edetate, camsylate, carbonate, chloride, caproate, caprylate, clavulanate, citrate, decanoate, dihydrochloride, dihydrogenphosphate, edetate, edisylate, estolato, esylate, ethylsuccinate, formate, fumarate, gluceptate, gluconate, glutamate, glycolate, glycolylarsanilate , heptanoate, hexin1,6-dioate, hexylresorcinate, hydrabamine, hydrobromide, hydrochloride, g hydroxybutyrate, iodide, isobutyrate, isothionate, lactate, lactobionate, laurate, malate, maleate, malonate, mandelate, mesylate, metaphosphate, methanesulfonate, methylsulfonate, monohydrogenphosphate, mucate, napsylate, naphthalen-1sulfonate, naphthalen-2-sulfonate, nitrate, oleate, oxalate, pamoate (embonate), palmitate, pantothenate, phenylacetates, phenylbutyrate, phenylpropionate, phthalate, phosphate / d-phosphate, polygalacturonate, propanesulfonate, propionate, propiolate , pyrophosphate, pyrosulfate, salicylate, stearate, subacetate, suberate, succinate, sulfate, sulfonate, sulfite, tanate, tartrate, theoclate, tosylate and valerate. Illustrative examples of suitable salts include organic salts derived from amino acids, such as glycine and arginine, ammonia, primary, secondary and tertiary amines and cyclic amines, such as piperidine, morpholine and piperazine, and inorganic salts derived from sodium, calcium, potassium, magnesium, manganese, iron, copper, zinc, aluminum and lithium. Compounds of the invention that include a basic moiety, such as an amino group, can form pharmaceutically acceptable salts with various amino acids, in addition to the aforementioned acids. Alternatively, useful compounds that are acidic in nature may be capable of forming basic salts with various pharmacologically acceptable cations. Examples of such salts include alkali metal or alkaline earth metal salts and, in particular, potassium and sodium salts. These salts are prepared using conventional techniques. The chemical bases that are used as reagents to prepare the pharmaceutically acceptable basic salts of the present invention are those that form non-toxic basic salts with the acidic compounds herein. These salts can be prepared by any suitable method, for example, treatment of the free acid with an organic or inorganic base, such as an amine (primary, secondary or tertiary), an alkali metal hydroxide, an alkaline earth metal hydroxide or the like. . These salts can also be prepared by treating the corresponding acidic compounds with an aqueous solution containing the desired pharmacologically acceptable cations and then evaporating the resulting solution to dryness, preferably under reduced pressure. Alternatively, they can also be prepared by mixing lower alkanolic solutions of the acidic compounds and the desired alkali metal alkoxide, and then evaporating the resulting solution to dryness in the same manner as before. In both cases, stoichiometric amounts of reactants are preferably used in order to ensure that the reaction is completed and that maximum yields of the desired final product are obtained. Chemical bases that can be used as reagents to prepare pharmaceutically acceptable basic salts of the compounds of the invention that are acidic in nature are those that form non-toxic basic salts with those compounds. Non-toxic basic salts include, but are not limited to, those derived from such pharmacologically acceptable cations, such as alkali metal cations (e.g., potassium and sodium) and alkaline earth metal cations (e.g., calcium and magnesium). ), ammonium or water-soluble amine addition salts, such as N-methylglucamine (meglumine), and the lower alkanolammonium salts and other pharmaceutically acceptable basic salts of organic amines. Hemisalts of acids and bases can also be formed, for example hemisulfate and hemicalcium salts. For a review of suitable salts, see Handbook of Pharmaceutical Salts: Properties, Selection, and Use by Stahl and Wermuth (Wiley VCH, 2002). Those skilled in the art are familiar with methods for making pharmaceutically acceptable salts of the compounds of the invention, and for interconverting salt and free base forms. The salts of the present invention can be prepared according to methods known to those of ordinary skill in the art. A pharmaceutically acceptable salt of the inventive compounds can be easily prepared by mixing solutions of the compound and the desired base or acid, as appropriate. The salt may precipitate from solution and be collected by filtration or it may be recovered by evaporation of the solvent. The degree of ionization in salt can vary from completely ionized to almost non-ionized. Those of ordinary skill in the art will understand that compounds of the invention in free base form having basic functionality can be converted to acid addition salts by treatment with a stoichiometric excess of the appropriate acid. The acid addition salts of the compounds of the invention can be reconverted to the corresponding free base by treating them with a stoichiometric excess of a suitable base, such as potassium carbonate or sodium hydroxide, typically in the presence of an aqueous solvent, and at a temperature of around 0 °C and 100 °C. The free base form can be isolated by conventional means, such as extraction with an organic solvent. Furthermore, the acid addition salts of the compounds of the invention can be exchanged by taking advantage of the differential solubilities of the salts, volatilities or acidities of the acids, or by treating them with the appropriately charged ion exchange resin. For example, the exchange may be affected by the reaction of a salt of the compounds of the invention with a slight stoichiometric excess of an acid of a lower pK than the acid component of the starting salt. Generally, this conversion is carried out at a temperature of about 0 °C to the boiling point of the solvent used as the medium for the procedure. Similar exchanges can be achieved with basic addition salts, generally using the free base form. The compounds of the invention can exist in unsolvated and solvated form. When the solvent or water is tightly bound, the complex has a well-defined stoichiometry independent of humidity. However, when the solvent or water is weakly bound, as in channel solvates and hygroscopic compounds, the water / solvent content will depend on humidity and drying conditions. In these cases, the usual thing is the absence of stoichiometry. The term solvate is used herein to describe a molecular complex comprising the compound of the invention and one or more pharmaceutically acceptable solvent molecules, for example, ethanol. The term hydrate is used when the solvent is water. Pharmaceutically acceptable solvates according to the invention include hydrates and solvates where the crystallization solvent can be isotopically substituted, for example, D2O, de-acetone, de-DMSO. The invention also relates to prodrugs of the compounds of the formulas provided herein. Therefore, some derivatives of the compounds of the invention, which may have little or no pharmacological activity, can be converted, when administered to a patient, into compounds of the invention, for example, by hydrolytic cleavage. Such derivatives are called prodrugs. More information on the use of prodrugs can be found in 'Prodrugs as Novel Delivery Systems, Vol. 14, ACS Symposium Series (T Higuchi and W iviA / a / zuzz / u 1 o / u j Stella); 'Bioreversible Carriers in Drug Desigri, Pergamon Press, 1987 (ed. E B Roche, American Pharmaceutical Association) and Guarino, V.R; Stella, V.J.: Biotech Pharm. Aspects 2007 5 (Pt2) 133187; their disclosures are incorporated herein in their entirety by reference. In one embodiment, a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V is a compound selected from Examples 1-164 or a pharmaceutically acceptable salt thereof. In one embodiment, a compound of any of Examples 1-164 may be in free base form. In one embodiment, a compound of any of Examples 1-164 may be in acid salt form. In one embodiment, certain compounds of Examples 1-164 are isolated as trifluoroacetate salts. The compounds provided herein may also contain unnatural ratios of atomic isotopes in one or more of the atoms constituting such compounds. That is, an atom, in particular when mentioned in relation to a compound according to Formula I, Formula I-A, Formula II, Formula III, Formula IV and Formula V, comprises all isotopes and isotopic mixtures of that atom, whether whether of natural origin or synthetically produced, whether in natural abundance or in isotopically enriched form. For example, when hydrogen is mentioned, it is understood that it refers to Ή,2H,3H or mixtures of these; When carbon is mentioned, it is understood that it refers to anC,12C,13C,14C or mixtures of these; When nitrogen is mentioned, it is understood that it refers to 13N,14N,15N or mixtures of these; When oxygen is mentioned, it is understood that it refers to 14O,15O,16O,17O,18O or mixtures of these; and when fluorine is mentioned, it is understood that it refers to 18F, 19F or mixtures of these. As noted above, the compounds provided herein also comprise compounds with one or more isotopes of one or more atoms, and mixtures thereof, including radioactive compounds, wherein one or more non-radioactive atoms have been replaced by one of their radioactive enriched isotopes. Radiolabeled compounds are useful as therapeutic agents, for example, anticancer therapeutic agents, research reagents, for example, assay reagents, and diagnostic agents, for example, in vivo imaging agents. All isotopic variations of the compounds provided herein, whether radioactive or not, are intended to be included within the scope of the present invention. Certain isotopically labeled compounds of the invention, for example those in which radioactive isotopes, such as 3H and 14C, are incorporated, are useful in substrate and / or drug tissue distribution assays. Tritiated, i.e., 3H, and carbon-14, i.e., 14C, isotopes are particularly preferred for their ease of preparation and detectability. Furthermore, substitution with heavier isotopes, such as deuterium, i.e., 2H, may provide certain therapeutic advantages that are a result of greater metabolic stability, for example, longer half-life in vivo or fewer dosage requirements, and thus, may be preferable in some circumstances. Generally, isotopically labeled compounds of the invention can be prepared by the procedures described in the Schemes and / or in the Examples and Preparations below, substituting an isotopically labeled reagent with an isotopically labeled reagent. non-isotopic. The invention also relates to prodrugs of the compounds of the formulas provided herein. Therefore, some derivatives of the compounds of the invention, which may have little or no pharmacological activity, can be converted, when administered to a patient, into compounds of the invention, for example, by hydrolytic cleavage. Such derivatives are called prodrugs. More information on the use of prodrugs can be found in Pro-drugs as Novel Delivery Systems, Vol. 14, ACS Symposium Series (T. Higuchi and W. Stella) and Bioreversible Carriers in Drug Design, Pergamon Press, 1987 (ed. E B Roche, American Pharmaceutical Association), the disclosures of which are incorporated herein by reference in their entirety. Prodrugs according to the invention can be produced, for example, by replacing suitable functionalities that are present in the inventive compounds with certain portions known to those of ordinary skill in the art as proportions, as described, for example, in Design of Prodrugs by H. Bundgaard (Elsevier, 1985), the disclosure of which is incorporated herein by reference in its entirety. Some non-limiting examples of prodrugs according to the invention include: (i) where the compound contains a carboxylic acid (-COOH) functionality, an ester thereof, for example replacement of hydrogen with (Cl-C8)alkyl; (ii) where the compound contains an alcohol functionality (-OH), an ether thereof, for example, replacement of hydrogen with (Cl-C6)alkanoyloxymethyl, or with an ether phosphate group; and (iii) where the compound contains a primary or secondary amino functionality (-NH2 or -NHR where R1H), an amide thereof, for example, the replacement of one or both hydrogens with a suitable metabolically labile group, such as a amide, carbamate, urea, phosphonate, sulfonate, etc. Other examples of replacement groups according to the previous examples and examples of other types of prodrug can be found in the aforementioned references. Finally, certain inventive compounds may act as potential prodrugs of other inventive compounds. Also included in the scope of the invention are metabolites of compounds of the formulas described herein, that is, compounds formed in vivo at the time of administration of the drug. For illustrative purposes, Chemical Reactions 1-10 show general methods for preparing the compounds provided herein as well as key intermediates. For a detailed description of each of the reaction steps, see the Examples section below. Those of mid-level skill will note that other synthetic routes may be used to synthesize the compounds of the invention. Although specific reagents and starting materials, discussed below, are represented in Chemical Reactions, they can be easily substituted with other reagents and starting materials to provide various derivatives and / or reaction conditions. Furthermore, many of the compounds prepared by the methods described below can be re-modified, based on this disclosure, using conventional chemistry known to those in the mid-level craft. 23 Chemical reaction 1 Chemical Reaction 1 describes the synthesis of intermediate 3 where X is halogen, which is useful for preparing compounds of Formula I where R1 and R2 are as defined for Formula I. Compound 1 can be cyclized with formamidine acetate in a solvent organic, such as EtOH, at elevated temperature to provide compound 2. Compound 2 can be alkylated with a reagent having the formula R'X where R1 is as defined for Formula I and X is halogen, in the presence of a base such as CS2CO3, in a solvent, such as DMF, to provide compound 3. Four. Five Chemical reaction 2 Chemical Reaction 2 describes the synthesis of intermediate 5, which is useful for preparing compounds of Formula I where R1 and R2 are as defined for Formula I and L is NH. Compound 3 (prepared, for example, according to Chemical Reaction 1) can be coupled with a reagent having the formula (PG)NH2 where PG is an amine protecting group (such as pmethoxybenzyl (PMB) or tert-butoxycarbonyl (Boc)) in the presence of a catalyst, such as a palladium catalyst (e.g., Pd2(dba)3) and a ligand (e.g., Xantphos) to provide compound 4. Compound 4 can be deprotected under standard conditions, for example by using TFA, to provide compound 5. iviA / a / zuzz / u 1 3 / uj 10 11 Chemical reaction 3 Chemical Reaction 3 describes the synthesis of intermediate 11 which is useful for preparing compounds of Formula I where R3, R4 and R5 are defined for Formula I. Compound 6 (where R3, R4 and R5 are as defined for Formula I) can be reacted with 1,2bis(chlorodimethyls¡l¡l)ethane in the presence of a strong base, such as n-butyllithium, in a suitable solvent, such as THF, at low temperatures, e.g. -78° C, to form l-aza-2,5disilacyclopentane, compound 7. Compound 7 can be reacted with iodine, in the presence of, for example, n-butyllithium or a comparable agent in a suitable solvent, such as THF, to provide compound 8. Compound 8 can be deprotected by reaction with an acid, such as HCl, in a suitable solvent, to provide compound 9. Compound 9 can be reacted with di-tert-butyl dicarbonate ((Boc)2O) in the presence of a catalyst, such as 4-dimethylaminopyridine (DMAP), in a suitable solvent, such as THF, to provide compound 10. Compound 10 can be deprotected in the presence of a base, such as K2CO3, in a suitable solvent, such as MeOH, to provide compound 11. Chemical reaction 4 Chemical Reaction 4 describes the synthesis of compound 13, which is a useful intermediate for preparing compounds of Formula I where R1, R2, R3, R4 and R5 are as defined for Formula I and L is NH. Compound 5 (prepared, for example, according to Chemical Reaction 2) can be coupled with compound 11 (prepared, for example, according to Chemical Reaction 3) in the presence of a catalyst (for example, a palladium catalyst , For example, Pd2(dba)3) and a ligand (e.g., Xantphos) followed by deprotection under standard conditions (e.g., with TFA), to provide compound 13. H..rR6o OO O Y + 'sz-------- X ,R R7Cl ClCl N R7 1516 Chemical reaction 5 Chemical Reaction 5 describes the synthesis of compound 16, which is useful for preparing compounds of Formula I where R6 and R7 are as defined for Formula I. Amine 14 can be coupled with sulfuryl dichloride 15 in the presence of a base, such as as TEA, in a suitable solvent, such as DCM, to provide compound 16. Chemical reaction 6 Chemical Reaction 6 describes the synthesis of a compound of Formula 24, which is useful for preparing compounds of Formula I where R1, R2, R3, R4 and R5 are as defined for the Formula and L is O. Compound 17 ( where R2 is as defined for Formula I) can be coupled with compound 18, where R3, R4 and R5 are as defined for Formula I, in a suitable solvent, such as DMSO, in the presence of a base, such as CS2CO3, at elevated temperature to provide compound 19. Compound 19 can be reacted with (Boc)2O in the presence of a catalyst, such as DMAP, in a suitable solvent, such as THF, to provide compound 20. The nitro group of compound 20 can be reduced under standard nitro reduction conditions, such as treatment with Fe and NH4Cl to provide compound 21. Compound 21 can be cyclized with formamidine acetate in an organic solvent, such as EtOH, at elevated temperature to provide compound 22. Compound 22 can be alkylated with a reagent having the formula R^ where R1 is as defined for Formula I and X is halogen, in the presence of a base such as Cs2CO3, in a solvent, such as DMF, to provide compound 23. Compound 23 can be deprotected under standard conditions (for example with TFA) to provide compound 24. Chemical reaction 7 Chemical Reaction 7 describes the synthesis of a compound of Formula 26, where R1, R2, R3, R4, R5, R6 and R7 are as defined for Formula I and L is NH (for example, prepared according to Chemical Reaction 4) or O (for example, prepared according to Chemical Reaction 6). Compound 25 can be coupled with compound 16 in the presence of a suitable base, such as pyridine, or in the presence of calcium triflimide in an organic solvent, such as toluene, at elevated temperatures, to provide compound 26. 16 Chemical reaction 8 Chemical Reaction 8 describes the synthesis of compound 27, which is useful for preparing compounds of Formula I wherein R3, R4, R5, R6 and R7 are as defined for Formula I. The amine 11, where R3, R4, R5, R6 and R7 are as defined for Formula I, can be coupled with sulfonamide chloride 16 where R6 and R7 are as defined for Formula I in the presence of a base, such as NaH, in a suitable solvent, such as THF , to provide compound 27. unprotect Scheme 9 Chemical Reaction 9 describes the synthesis of a compound of Formula 29, which is a compound of Formula I where R1, R2, R3, R4, R5, R6 and R7 are as defined for Formula I. Compound 5 (prepared , for example, according to Chemical Reaction 2), where R1 and R25 are as defined for Formula I, can be coupled with compound 27 (prepared, for example, according to Chemical Reaction 8), where R3, R4, R5, R6 and R7 are as defined for Formula I and PG is an amine protecting group (such as p-methoxybenzyl (PMB) or tert-butoxycarbonyl (Boc)), in the presence of a catalyst (e.g. a palladium catalyst, e.g. Pdz(dba)3) and a ligand (e.g. Xantphos) followed by deprotection under standard conditions (e.g. with TFA) to provide compound 29. R5 Amine protection unprotect R5 NaH unprotect Chemical reaction 10 Chemical Reaction 10 describes the synthesis of compound 33, which is a compound of Formula I where R1, R2, R3, R4 and R5 are as defined for Formula I and L is O. The amine group of compound 24 (where R1, R2, R3, R4 and R5 are as defined for Formula I) can be deprotected with a suitable amine protecting group (for example, p-methoxybenzyl (PMB) or tert-butoxycarbonyl (Boc)) by reacting with a suitable reagent ( for example, by reacting with (Boc)2O in the presence of a catalyst, such as DMAP, in a suitable solvent, such as THF) to provide compound 30, wherein PG is an amine protecting group (for example, pmethoxybenzyl (PMB) or tert-butoxycarbonyl (Boc)). Compound 30 can be deprotected under suitable conditions (for example, in the presence of K2CO3 in an organic solvent, such as MeOH, at elevated temperature) to provide monoprotected compound 31. Compound 31 can be coupled with sulfamoyl chloride 16 in the presence of a base, such as NaH, in a suitable solvent, such as THF, to provide compound 32. Compound 32 can be deprotected under standard conditions (e.g., with TFA ), to provide compound 33. The processes shown in Chemical Reactions 1-10 are useful for preparing compounds of Formulas II, III and IV, as well as for preparing intermediates useful for preparing compounds of Formulas II, III and IV. In one embodiment, provided herein is a process for preparing a compound of Formula I or a pharmaceutically acceptable salt thereof comprising: (a) for a compound of Formula I where L, R1, R2, R3, R4, R5, R5 and R7 are as defined for Formula I, coupling a compound having Formula (25) R5 where L, R1, R2, R3, R4 and R5 are as defined for Formula I, with a compound having Formula (16) Cl'SU R7where R6 and R7 are as defined for Formula I, in the presence of a suitable base; or (b) for a compound of Formula I where R1, R2, R3, R4 and R5 are as defined for Formula I and L is NH, react a compound of Formula (5) 1-N R1 EITHER NH2 R2where R1 and R2 are as defined for Formula I, with a compound having Formula (27) wherein R3, R4, R5, R6 and R7 are as defined for Formula I and PG is an amine protecting group, in the presence of a palladium catalyst and a ligand, followed by removal of the amine protecting group; or (c) for a compound of Formula I where R1, R2, R3, R4 and R5 are as defined for Formula I and L is O, reacting a compound having Formula (31) R5 where R1, R2, R3, R4 and R5 are as defined for Formula I and PG is an amine protecting group, with a reagent having the formula V 6 crs'N'R R7in the presence of a base, followed by removal of the amine protecting group; and optionally forming a pharmaceutically acceptable salt thereof. The compounds of Formulas 3, 5, 12, 13, 19, 20, 21, 22, 23, 24, 25, 28, 21 and 32 are synthetic intermediates useful for the preparation of compounds of Formula I, and are an aspect additional to this invention. The term "amine protecting group" as used herein refers to a derivative of the groups commonly employed to block or protect an amino group while carrying out reactions on other functional groups of the compound. Examples of suitable protecting groups for use in any of the processes described herein include carbamates, amides, alkyl and aryl groups, mines, as well as many derivatives of N-heteroatoms that can be removed to regenerate the desired amine group. Non-limiting examples of amine protecting groups are t-butyloxycarbonyl (Boc), 2-trimethylsilylethoxymethyl (SEM) and p-methoxybenzyl (PMB). Other examples of these groups, and other protective groups, are found in T. W. Greene, etal., Greene's Protective Groups in Organic Synthesis. New York: Wiley Interscience, 2014. The compounds of Formula I, Formula I-A, Formula II, Formula III, Formula IV and Formula V or a pharmaceutically acceptable salt thereof are useful for treating diseases and disorders that can be treated with a BRAF kinase inhibitor. , such as BRAF-associated diseases and disorders, for example, proliferative disorders such as cancers, including solid tumors. The ability of the test compounds to act as BRAF inhibitors can be demonstrated by the enzymatic assay described in Example Al, the cellular assay described in Example A2, the cellular assay described in Example A3 and the proliferation assay described in Example A4. ICso values ​​are shown in Tables Al and A2. In some embodiments, certain compounds of Formula I, Formula I-A, Formula II, Formula III, Formula IV and Formula V, or a pharmaceutically acceptable salt thereof, exhibit surprising penetration into the brain and / or or the CNS. Such compounds are capable of crossing the BBB and inhibiting a BRAF kinase in the brain and / or other CNS structures. In some embodiments, the compounds provided herein are capable of crossing the BBB in a therapeutically effective amount. For example, treatment of a subject with cancer (e.g., a type of BRAF-associated cancer, such as a type of BRAF-associated CNS cancer) may include administration (e.g., oral administration) of a compound of the Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, to the subject. Accordingly, in some embodiments, the compounds provided herein are useful for treating a type of CNS cancer. As used herein, the terms treat or treatment refer to therapeutic or palliative measures. Beneficial or desired clinical outcomes include, but are not limited to, relief, in whole or in part, of symptoms associated with a disease or disorder or condition, decreased extent of disease, stabilized state (i.e., no worsening) of the disease, delay or slowing of the progression of the disease, improvement or palliation of the disease state (for example, one or more symptoms of the disease) and remission (whether partial or total), whether detectable or undetectable. However, treating or treatment may also include therapeutic measures (e.g., inhibition of BRAF kinase in a BRAF-associated tumor) that temporarily worsen the appearance and / or symptoms of the subject. As used herein, the terms treat and treat when referring to, for example, the treatment of a type of cancer, are not intended to be absolute terms. For example, cancer treatment and cancer treatment, as used in a clinical setting, is intended to include obtaining beneficial or desired clinical results and may include an improvement in the condition of a subject who has cancer. Beneficial or desirable results include, but are not limited to, one or more of the following: reduction in the proliferation (or destruction) of neoplastic or cancer cells, inhibition of metastasis of neoplastic cells, reduction of metastasis in a subject, reduction in size of a tumor, change in the growth rate of one or more tumors in a subject, increase in the remission period for a subject (for example, compared to one or more metrics in a subject having a similar type of cancer without treatment or a different treatment, or compared to one or more metrics in the same subject before treatment), decreased symptoms resulting from a disease, increased quality of life of those suffering from a disease (e.g., assessed using FACT- G or EORTC-QLQC30), reducing the dose of other medications necessary to treat a disease, delaying the progression of a disease and / or prolonging the survival of subjects suffering from a disease. Treatment may also mean prolonging survival compared to the expected survival if not receiving treatment, for example, an increase in overall survival (OS) compared to a subject not receiving treatment as described herein, and / or an increase in progression free survival (PFS) compared to a subject not receiving treatment as described herein. As used herein, the term subject refers to any animal, including mammals, such as mice, rats, other rodents, rabbits, dogs, cats, pigs, swine, sheep, horses, primates or humans. In some embodiments, the subject is a human being. In some embodiments, the subject has experienced and / or exhibited at least one symptom of the disease or disorder to be treated and / or prevented. In some embodiments, the subject has been identified or diagnosed as having a tumor with a BRAF mutation (a BRAF-associated tumor) (e.g., as determined by use of an assay or kit approved by a regulatory agency, for example, approved by the FDA). In some embodiments, the subject has a tumor that is positive for a BRAF mutation (e.g., as determined by use of an assay or kit approved by a regulatory agency). The subject may be a subject whose tumors have a BRAF mutation (for example, when the tumor is identified as such through the use of a kit or assay approved by a regulatory agency, for example, approved by the FDA). In some embodiments, the subject is suspected of having a BRAF-associated tumor. In some embodiments, the subject has a clinical record indicating that the subject has a tumor that has a BRAF mutation (and optionally the clinical record indicates that the subject should be treated with any of the compositions provided herein). In some embodiments, the subject is a human being. In some embodiments, the human subject is a pediatric subject. The term pediatric subject as used herein refers to a subject under 21 years of age at the time of diagnosis or treatment. The term pediatric can be divided into several subpopulations that include: newborns (from birth to the first month of life); infants (1 month to two years old); children (two years to 12 years); and adolescents (ages 12 to 21 (up to but not including the twenty-second birthday)). Berhman RE, Kliegman R, Arvin AM, Nelson WE, Nelson Textbook of Pediatrics, 15thEd. Philadelphia: W.B. Saunders Company, 1996; Rudolph AM, et al. Rudoiph's Pediatrics, 21stEd. New York: McGraw-Hill, 2002; and Avery MD, First LR. Pediatric Medicine, 2ndEd. Baltimore: Williams & Wilkins; 1994. In some embodiments, a pediatric subject is from birth to the first 28 days of life, from 29 days to less than two years, from two years to less than 12 years, or from 12 years to 21 years of age (up to but not including your twenty-second birthday). In some embodiments, a pediatric subject is from birth to the first 28 days of life, from 29 days to less than 1 year of age, from one month of age to less than four months of age, from three months from age to less than seven months of age, from six months of age to less than 1 year of age, from 1 year of age to less than 2 years of age, from 2 years of age to less than 3 iviA / a / zuzz / u i o i u □ years of age, from 2 years of age to less than seven years, from 3 years to less than 5 years, from 5 years to less than 10 years, from 6 years to less than 13 years, from 10 years of age to less than 15 years, or from 15 years to less than 22 years. In certain embodiments, the compounds of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, are useful for preventing diseases and disorders as defined at the moment. The term prevent, as used herein, means the prevention of the onset, recurrence or spread, in whole or in part, of the disease or condition as described herein. The term BRAF-associated with respect to a disease or disorder as used herein refers to diseases or disorders associated with or having one or more BRAF mutations and / or BRAF fusions. Non-limiting examples of a BRAF-associated disease or disorder include, for example, BRAF-associated tumors. The phrase BRAF mutation refers to a genetic mutation (for example, a chromosomal translocation that results in one or more mutations in a BRAF gene that results in the expression of a BRAF protein with one or more point mutations compared to a protein BRAF wild-type), or an alternatively spliced ​​version of a BRAF mRNA that results in a BRAF protein that has a deletion of at least one amino acid in the BRAF protein compared to the wild-type BRAF protein (i.e., a splicing variant). Non-limiting examples of BRAF mutations include BRAF Class I mutations (e.g., BRAF V600 mutations, e.g., BRAF V600E and BRAF V600K), BRAF Class II mutations (e.g., BRAF non-V600 mutations and BRAF splice variants), and BRAF class III mutations. The term BRAF class I mutations refers to BRAF V600 mutations that signal as active monomers independent of Ras. Examples include BRAF V600E and BRAF V600K mutations. The term BRAF class Π mutations includes (i) non-V600 BRAF mutations that function as RAS-independent activated dimers of BRAF and / or CRAF and (i) BRAF splice variants that depend on dimerization for activity. in a RAS independently. Examples of non-V600 BRAF mutations (class II) include G469A, G469R, G469V, K601E, K601N, K601T, L597Q, and L597V. In one embodiment, the non-V600 BRAF mutation is G469A. The term BRAF splice variant refers to aberrantly spliced ​​BRAF V600E forms. BRAF splice variants are BRAF V600E resistance mutations that lack exons encoding part of the RAS binding domain and exhibit enhanced dimerization in cells with low levels of RAS activation (Poulikakos et al., Nature, 480 (7377): 387-390. Examples of BRAF V600E splice variants include those lacking exons 4-8 (also known as p61BRAF (V600E)), exons 4-10, exons 2-8, or exons 2-10. embodiment, the resistance mutation is p61BRAF (V600E). The term resistance mutation refers to a mutation in a BRAF V600E mutation that occurs after exposure of the BRAF V600E mutant to a BRAF inhibitor, either alone or in combination with another anticancer agent such as a MEK inhibitor. Tumors that have resistance mutations become less sensitive (for example, resistant to treatment with) BRAF inhibitor. In one embodiment, the resistance mutation occurs after exposure to vemurafenib. The term BRAF class III mutations refers to non-V600 BRAF mutations that function as RAS-dependent activated dimers of BRAF and / or CRAF. Non-limiting examples of BRAF class III mutations include G466A, G466E, G466R, G466V, D594A, D594E, D594G, D594H, G594N, D287H, V549L, S467A, S467E, S467L, G469E, N581S, N581I, F595L, 96A, G596C, G596D, G596R, and K483M. The term BRAF fusion refers to a translocation of the BRAF gene that results in the expression of a fusion protein. In one embodiment, a BRAF-associated tumor or BRAF-associated cancer has one or more BRAF fusions that lead to constitutive activation and transformation of the kinase, including, but not limited to, KIAA11549-BRAF, MKRN1-BRAF, TRIM24 -BRAF, AGAP3-BRAF, ZC3HAV1-BRAF, AKAP9-BRAF, CCDC6-BRAF, AGK-BRAF, EPS15-BRAF, NUP214-BRAF, ARMC10-BRAF, BTF3L4-BRAF, GHR-BRAF, ZC3HAV1-BRAF, ZNF767-BRAF , CCDC91BRAF, DYNC112-BRAF, ZKSCAN1-BRAF, GTF2I-BRAF, MZT1-BRAF, RAD18-BRAF, CUX1-BRAF, SLC12A7-BRAF, MYRIP-BRAF, SND1-BRAF, NUB1-BRAF, KLHL7-BRAF, TANK-BRAF , RBMS3-BRAF, STRN3-BRAF, STK35-BRAF, ETFA-BRAF, SVOPL-BRAF, JHDM1D-BRAF, or BCAP29-BRAF. The term BRAF-associated tumor or BRAF-associated cancer as used herein refers to tumors or types of cancer associated with or having a BRAF mutation and includes tumors having a BRAF V600 class I mutation, e.g. , a BRAF V600E or V600K mutation, and tumors that have a BRAF class II mutation. BRAF-associated tumors include both benign BRAF-associated tumors and malignant BRAF-associated tumors (i.e., BRAF-associated cancers). The term tumor, as used herein, refers to an abnormal growth of tissue that arises from uncontrolled, usually rapid, cellular proliferation. The tumor can be benign (non-cancerous) or malignant (that is, cancer). The tumor may be a solid or liquid tumor (that is, a hematological tumor, also known as blood cancer). The term wild type describes a nucleic acid (for example, a BRAF gene or a BRAF mRNA) that is typically found in a subject that does not have a disease or disorder related to the reference nucleic acid or protein. The term wild-type BRAF describes a BRAF nucleic acid (e.g., a BRAF gene or a BRAF mRNA) or a BRAF protein that is found in a subject who does not have a BRAF-associated disease, e.g., a BRAF-associated cancer. BRAF (and, optionally, is also not at increased risk of developing a BRAF-associated disease and / or is not suspected of having a BRAF-associated disease), or is found in a cell or tissue from a subject who does not have an associated disease to BRAF, for example, a BRAF-associated cancer (and optionally also have no increased risk of developing a BRAF-associated disease and / or are not suspected of having a BRAF-associated disease). The term regulatory agency refers to a country's agency for approving the medical use of pharmaceutical agents with the country. For example, a non-limiting example of a regulatory agency is the United States Food and Drug Administration (FDA). Provided herein is a method of treating a BRAF-associated tumor, in a subject in need of such treatment, the method comprising administering to the subject a therapeutically effective amount of a compound of Formula I, Formula I-A, Formula II, Formula III , Formula IV or Formula V, or a pharmaceutically acceptable salt thereof or a pharmaceutical composition thereof. For example, provided herein are methods for treating a BRAF-associated tumor in a subject in need of such treatment, the method comprising a) detecting a BRAF mutation in a sample from the subject; and b) administering a therapeutically effective amount of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In some embodiments, the BRAF mutation is a class I mutation. In some embodiments, the BRAF class I mutation is BRAFV600E. In some embodiments, the BRAF mutation is a class II mutation. In some embodiments, the class II mutation is a non-V600 mutation. In some embodiments, the non-V600 mutation is G469A. In some embodiments, the class II mutation is a splice variant of BRAF V600E. In some embodiments, the BRAF V600E splice variant is p61BRAF (V600E). In some embodiments of any of the methods of use described herein, the BRAF-associated tumor is a solid tumor. In some embodiments, the tumor is intracranial. In some embodiments, the tumor is extracranial. In some embodiments of any of the methods of use described herein, the BRAF-associated tumor is a malignant BRAF-associated tumor (i.e., a BRAF-associated cancer). In some embodiments of any of the methods of use described herein, the cancer is melanoma, colon cancer, colorectal cancer, lung cancer (for example, small cell lung cancer or non-small cell lung cancer ), thyroid cancer (for example, papillary thyroid cancer, medullary thyroid cancer, differentiated thyroid cancer, recurrent thyroid cancer, or refractory differentiated thyroid cancer), breast cancer, bladder cancer, ovarian cancer (carcinoma of ovary), CNS cancer (including gliomas and LMD), bone cancer, cancer of the anus, anal canal or anorectum, angiosarcoma, adenoid cystic carcinoma, appendix cancer, eye cancer, bile duct cancer (cholangiocarcinoma), cancer of the cervix, ductal carcinoma in situ, endometrial cancer, gallbladder, hepatobiliary cancer, hepatopancreato-biliary carcinoma, squamous cell carcinoma of the head and neck, oral cancer, oral cavity cancer, leukemia, lip cancer, oropharyngeal cancer , cancer of the nose, nasal cavity or middle ear, vulvar cancer, esophageal cancer, esophagogastric cancer, cervical cancer, gastrointestinal carcinoid tumor, gastrointestinal neuroendocrine cancer, hypopharyngeal cancer, kidney cancer, laryngeal cancer, cancer of the liver, nasopharyngeal cancer, non-Hodgkin lymphoma, peripheral nervous system cancers (e.g., neuroblastoma), neuroendocrine cancer, pancreatic cancer, peritoneum, plasma cell neoplasm, omentum and mesentery cancer, pharyngeal cancer, prostate, kidney cancer (for example, renal cell carcinoma (RCC)), small intestine cancer, small intestine cancer, soft tissue sarcoma, stomach cancer, testicular cancer, uterine cancer, ureter cancer, or cancer of urinary bladder. In one embodiment, the BRAF-associated cancer is a CNS cancer, melanoma, colorectal cancer, thyroid cancer, non-small cell lung cancer, ovarian cancer, renal cell carcinoma, or a primary brain tumor. In some embodiments, the BRAF-associated cancer is an extracranial cancer selected from melanoma, colorectal cancer, thyroid cancer, non-small cell lung cancer, ovarian cancer, and neuroblastoma. In some embodiments, the BRAF-associated cancer is a melanoma. In some embodiments, the BRAF-associated cancer is colorectal cancer. In some embodiments, the BRAF-associated cancer is thyroid cancer. In some embodiments, the BRAF-associated cancer is non-small cell lung cancer. In some embodiments, the BRAF-associated cancer is ovarian cancer. In some embodiments, the BRAF-associated cancer is neuroblastoma. In some embodiments, the BRAF-associated cancer is an intracranial cancer (brain cancer). In some embodiments, the BRAF-associated cancer is a CNS cancer. In some embodiments, the BRAF-associated cancer is a CNS cancer. In some embodiments, the BRAF-associated cancer is a cancer that has a BRAF V600E or BRAF V600K mutation. In some embodiments, BRAF-associated cancer having a BRAF V600E or BRAF V600K mutation is selected from melanoma, colorectal cancer, thyroid cancer, non-small cell lung cancer, ovarian cancer, renal cell carcinoma and types. of metastatic cancers of these and primary brain tumors. In some embodiments, the BRAF-associated cancer having a BRAF V600E or BRAF V600K mutation is a CNS tumor. In some embodiments, the CNS tumor is a malignant tumor (a CNS cancer). In some embodiments, the malignant tumor is a metastatic CNS cancer. In some embodiments, the metastatic CNS cancer is selected from metastatic melanoma, metastatic colorectal cancer, metastatic non-small cell lung cancer, metastatic thyroid cancer, and metastatic ovarian cancer. In some embodiments, the CNS tumor is intracranial LMD or extracranial LMD. In some embodiments, the BRAF-associated cancer is a cancer that has a BRAF class II mutation. In one embodiment, the cancer having a BRAF class II mutation is selected from lung cancer (e.g., non-small cell lung cancer), melanoma, colorectal cancer, breast cancer, pancreatic cancer, pancreatic cancer. thyroid, prostate cancer, adenoid cystic carcinoma, appendiceal cancer, small intestine cancer, gastrointestinal neuroendocrine cancer, head and neck squamous cell carcinoma, angiosarcoma, bladder cancer, plasma cell neoplasm, hepatobiliary cancer, hepatopancreatobiliary carcinoma, liver cancer ovarian cancer, endometrial cancer, neuroendocrine cancer, cholangiocarcinoma, esophagogastric soft tissue sarcoma, leukemia, non-Hodgkin lymphoma, and CNS cancers (e.g., gliomas). In one embodiment, the cancer has a BRAF G469A mutation. In some embodiments, the BRAF-associated cancer is a cancer that has a class III BRAF mutation. In one embodiment, the cancer having a BRAF class III mutation is selected from melanoma, small intestine cancer, colorectal cancer, non-small cell lung cancer, endometrial cancer, cervical cancer, leukemia, cancer. bladder, non-Hodgkin lymphoma, glioma, ovarian cancer, prostate cancer, hepatobiliary cancer, esophagogastric cancer, soft tissue sarcoma and breast cancer. In one embodiment, the cancer has a BRAF G466V or BRAF D594G mutation. In one embodiment, the cancer has a BRAF G466V mutation. In one embodiment, the cancer has a BRAF D594G mutation. In one embodiment, the BRAF-associated tumor has a BRAF fusion protein, where the tumor is breast carcinoma (e.g., invasive ductal carcinoma of the breast), colorectal carcinoma (e.g., colon adenocarcinoma), esophagus (e.g., esophageal adenocarcinoma), glioma (e.g., infantile desmoplastic cerebral ganglioglioma, cerebral pilocytic astrocytoma, cerebral pleomorphic xanthoastrocytoma, low-grade glioma (NOS) of the spinal cord, anaplastic oligodendroglioma, anaplastic ganglioglioma), head carcinoma and neck (e.g., head and neck, lung adenocarcinoma) non-small cell lung cancer (NOS), melanoma (e.g., spitzoid cutaneous melanoma, non-spitzoid mucosal melanoma, spitzoid cutaneous melanoma, unknown primary melanoma, non-spitzoid cutaneous melanoma spitzoid), pancreatic carcinoma (e.g., adenocarcinoma, pancreatic acinar cell carcinoma), prostate carcinoma (e.g., acinar adenocarcinoma of the prostate), sarcoma (malignant solid fibrous tumor), thyroid carcinoma (PAP thyroid carcinoma pilaris), carcinoma unknown primary (e.g., unknown primary, adenocarcinoma), pleural mesothelioma, rectal adenocarcinoma, uterine endometrial carcinoma (e.g., uterine endometrial adenocarcinoma (NOS)), or ovarian serous carcinoma. In one embodiment, BRAF-associated cancer is selected from cancer types having the BRAF fusion proteins described in Table 1 (J.S. Ross, et al., Int. J. Cancer: 138, 881-890 ( 2016)). Table 1. Example BRAF fusion components and cancer types iviA / a / zuzz / u i o / u j Tumor group histology tumor type fusion breast carcinoma BCAP29-BRAF breast carcinoma metastatic breast carcinoma KIAA11549-BRAF colorectal carcinoma primary colon adenocarcinoma MKRN1-BRAF colorectal carcinoma metastatic colon adenocarcinoma TRIM24-BRAF colorectal carcinoma primary colon adenocarcinoma AGAP3- BRAF esophageal carcinoma primary esophageal adenocarcinoma ZC3HAV1-BRAF primary cerebral desmoplastic infantile ganglioglioma glioma KIAA11549-BRAF primary cerebral pilocytic astrocytic glioma KIAA11549-BRAF primary cerebral pleomorphic xanthoastrocytoma glioma KIAA11549-BRAF glioma primary spinal cord low-grade glioma (NOS) KIAA1154 9- BRAF primary cerebral pilocytic astrocytic glioma AKAP9-BRAF primary cerebral pleomorphic xanthoastrocytoma glioma CCDC6-BRAF primary cerebral pleomorphic xanthoastrocytoma glioma AGK-BRAF non-pilocytic glioma; primary anaplastic oligodendroglioma AGK-BRAF non-pilocytic glioma; primary anaplastic ganglioglioma KIAA11549-BRAF head carcinoma primary neuroendocrine carcinoma MKRN1-BRAF and neck head and neck lung carcinoma metastatic lung adenocarcinoma EPS15-BRAF lung carcinoma primary non-small cell lung (NOS) lung cancer NUP214-BRAF lung carcinoma primary lung adenocarcinoma ARMC10-BRAF lung carcinoma lung adenocarcinoma primary BTF3L4-BRAF lung carcinoma primary lung adenocarcinoma AGK-BRAF lung carcinoma metastatic lung adenocarcinoma GHR-BRAF lung carcinoma primary lung adenocarcinoma ZC3HAV1-BRAF lung carcinoma primary non-small cell lung cancer (NOS) TRIM224-BRAF melanoma primary spitzoid cutaneous melanoma TRIM24-BRAF melanoma metastatic non-spitzoid mucosal melanoma ZNF767-BRAF melanoma metastatic non-spitzoid cutaneous melanoma CCDC91-BRAF melanoma primary spitzoid cutaneous melanoma DYNC112-BRAF melanoma metastatic spitzoid cutaneous melanoma AKAP9-BRAF melanoma metastatic spitzoid cutaneous melanoma ZKSCAN1-BRAF melanoma unknown primary metastatic melanoma GTF2I-BRAF melanoma metastatic non-spitzoid cutaneous melanoma AGAP3-BRAF melanoma metastatic spitzoid cutaneous melanoma AGK-BRAF melanoma metastatic spitzoid cutaneous melanoma MZT1-BRAF melanoma primary non-spitzoid cutaneous melanoma RAD18-BRAF melanoma metastatic spitzoid cutaneous melanoma CUX1-BRAF melanoma metastatic spitzoid cutaneous melanoma SLC12A7-BRAF pancreatic carcinoma primary pancreatic ductal adenocarcinoma MYRIP-BRAF metastatic acinar cell carcinoma carcinoma SND1-BRAF IVIA / a / ¿U¿¿ / U I O / U3 pancreas pancreas prostate carcinoma metastatic prostate acinar adenocarcinoma NUBl-BRAF sarcoma primary malignant solid fibrous tumor KIAA1549-BRAF thyroid carcinoma primary papillary thyroid carcinoma KLHL7-BRAF thyroid carcinoma primary papillary thyroid carcinoma TANK-BRAF thyroid carcinoma papillary carcinoma metastatic thyroid RBMS3-BRAF unknown primary carcinoma unknown primary metastatic adenocarcinoma STRN3-BRAF unknown primary carcinoma unknown primary carcinoma (NOS) metastatic SND1-BRAF pleural mesothelioma primary pleural mesothelioma STK35-BRAF rectal adenocarcinoma metastatic rectal adenocarcinoma ETFA-BRAF endometrial carcinoma of uterus metastatic uterine endometrial adenocarcinoma (NOS) SVOPL-BRAF serous ovarian carcinoma metastatic serous ovarian carcinoma JHDM1D-BRAF The term metastasis is a term known in the art that refers to the spread of cancer cells from the place where they first formed (the primary site) to one or more sites in a subject (one or more secondary sites). In metastasis, cancer cells break away from the original (primary) tumor, travel through the blood or lymph system, and form a new tumor (a metastatic tumor) in other organs or tissues in the body. The new metastatic tumor includes cancer cells that are the same or similar to the primary tumor. At the secondary site, the tumor cell can proliferate and begin the growth or colonization of a secondary tumor at this distant site. The term metastatic cancer (also known as secondary cancer) as used herein refers to a type of cancer that originates in one type of tissue, but then spreads to one or more tissues outside the origin of the cancer (primary). . Metastatic brain cancer refers to cancer in the brain, that is, cancer that originated in tissue other than the brain and has metastasized to the brain. In one embodiment, the BRAF-associated tumor is a malignant BRAF-associated CNS tumor (i.e., a BRAF-associated CNS cancer). The term CNS cancer or CNS cancer or as used interchangeably herein refers to a cancer (i.e., malignant tumor) of the CNS, including types of brain cancer (also known as intracranial tumors), types of spinal cord cancer and types of cancer of the meninges that surround the brain and spinal cord. The term BRAF-associated CNS cancer refers to CNS cancer associated with or having a BRAF mutation. CNS cancers include metastatic brain cancers and malignant primary brain tumors. In one embodiment, the BRAF-associated CNS cancer is a BRAF-associated metastatic brain cancer. BRAF-associated metastatic brain cancer may result from any cancer described herein, wherein the subject has developed at least one brain metastasis. In one embodiment, the BRAF-associated metastatic brain cancer is metastatic melanoma, metastatic colorectal cancer, or metastatic non-small cell lung cancer. In one embodiment, the BRAF-associated metastatic brain cancer is metastatic melanoma. In one embodiment, the BRAF-associated metastatic brain cancer is metastatic colorectal cancer. In one embodiment, the BRAF-associated metastatic brain cancer is metastatic non-small cell lung cancer. In one embodiment, the BRAF-associated metastatic brain cancer is metastatic ovarian cancer. In one embodiment, the metastatic brain cancer is metastatic thyroid cancer. In one embodiment, the BRAF-associated metastatic brain cancer is kidney cancer. In one embodiment, the cancer is a BRAF-associated metastatic cancer with at least one brain metastasis (i.e., a metastatic brain cancer). In one embodiment, the cancer is a BRAF-associated metastatic melanoma with at least one brain metastasis. In one embodiment, the cancer is BRAF-associated metastatic colorectal cancer with at least one brain metastasis. In one embodiment, the cancer is a BRAF-associated metastatic non-small cell lung cancer with at least one brain metastasis. In one embodiment, the cancer is BRAF-associated metastatic ovarian cancer with at least one brain metastasis. In one embodiment, the cancer is BRAF-associated metastatic thyroid cancer with at least one brain metastasis. In one embodiment, the cancer is a BRAF-associated neuroblastoma with at least one brain metastasis. Leptomeningeal metastases (leptomeningeal disease (LMD)) represent a subset of CNS metastases that grow in the lining of the brain or spine and / or in the cerebrospinal fluid (CSF), or leptomeningeal carcinomatosis. In mammals, the meninges are the dura mater, the arachnoid mater, and the pia mater. The CSF is located in the subarachnoid space between the arachnoid and the pia mater. The arachnoid and pia mater together are sometimes called the leptomeninges. When LMD occurs in the leptomeninges and / or CSF surrounding the spinal cord, it may be called extracranial LMD. When LMD occurs in the leptomeninges and / or CSF of the brain, it may be called intracranial LMD. Because LMD cancer cells can be suspended in the CSF, they can spread rapidly throughout the CNS. As a result, LMD has a poor prognosis, and survival is usually measured in months. In one embodiment, the metastatic cancer is BRAF-associated LMD. In one embodiment, the metastatic cancer is BRAF-associated intracranial LMD. In one embodiment, the metastatic cancer is BRAF-associated extracranial LMD. BRAF-associated cancers with the highest incidence of leptomeningeal metastases are lung cancer and melanoma. In one embodiment, the BRAF-associated LMD is LMD derived from melanoma metastases (i.e., the LMD is metastatic melanoma). In one embodiment, the BRAF-associated LMD is LMD derived from colorectal cancer metastases (i.e., the LMD is metastatic colorectal cancer). In one embodiment, the BRAF-associated LMD is LMD derived from colorectal cancer metastases (i.e., the LMD is metastatic colorectal cancer). In one embodiment, the cancer is a BRAF-associated cancer that has a high risk of metastasis. In one embodiment, the BRAF-associated cancer that has a high risk of metastasis is a cancer that has a BRAF V600E or BRAF V600K mutation. In one embodiment, the BRAF-associated cancer that has a high risk of metastasis is melanoma, colorectal cancer, thyroid cancer, non-small cell lung cancer, ovarian cancer, or neuroblastoma. In one embodiment, the BRAF-associated cancer that has a high risk of metastasis is melanoma, colorectal cancer, thyroid cancer, non-small cell lung cancer, ovarian cancer, or neuroblastoma, each of which has a mutation. BRAF V600E or BRAF V600K. In one embodiment, the BRAF-associated cancer that has a high risk of metastasis is melanoma. In one embodiment, the BRAF-associated cancer that has a high risk of metastasis is melanoma having a BRAF V600E mutation or a BRAF V600K mutation. In one embodiment, the BRAF-associated cancer that has a high risk of metastasis is colorectal cancer. In one embodiment, the BRAF-associated cancer that has a high risk of metastasis is colorectal cancer that has a BRAF V600E mutation or a BRAF V600K mutation. In one embodiment, the BRAF-associated cancer that has a high risk of metastasis is thyroid cancer. In one embodiment, the BRAF-associated cancer that has a high risk of metastasis is thyroid cancer that has a BRAF V600E mutation or a BRAF V600K mutation. In one embodiment, the BRAF-associated cancer that has a high risk of metastasis is non-small cell lung cancer. In one embodiment, the BRAF-associated cancer that has a high risk of metastasis is non-small cell lung cancer that has a BRAF V600E mutation or a BRAF V600K mutation. In one embodiment, the BRAF-associated cancer that has a high risk of metastasis is ovarian cancer. In one embodiment, the BRAF-associated cancer that has a high risk of metastasis is an ovarian cancer that has a BRAF V600E mutation or a BRAF V600K mutation. In one embodiment, the BRAF-associated cancer that has a high risk of metastasis is neuroblastoma. In one embodiment, the BRAF-associated cancer that has a high risk of metastasis is neuroblastoma having a BRAF V600E mutation or a BRAF V600K mutation. In one embodiment, the cancer is a BRAF-associated cancer having a class II mutation. In one embodiment, the class II mutation is a non-V600 mutation. In one embodiment, the non-V600 mutation is G469A, G469R, G469V, K601E, K601N, K601T, L597Q or L597V. In one embodiment, the non-V600 mutation is G469A. In one embodiment, the class II mutation is a BRAF splice variant. In one embodiment, the BRAF splice variant lacks exons 4-8 (also known as p61BRAF(V600E)), exons 4-10, exons 2-8, or exons 2-10. In one embodiment, the BRAF splice variant is p61BRAF(V600E). Non-limiting examples of BRAF-associated cancer types with class II mutations include lung cancer (e.g., non-small cell lung cancer and small cell lung cancer), melanoma, colorectal cancer, breast cancer, pancreatic cancer, thyroid cancer, prostate cancer, adenoid cystic carcinoma, appendiceal cancer, small intestine cancer, squamous cell carcinoma of the head and neck, angiosarcoma, bladder carcinoma, plasma cell neoplasm, hepatopancreato-biliary carcinoma, liver cancer ovary, neuroendocrine cancer, cholangiocarcinoma and CNS tumors. In one embodiment, the BRAF-associated cancer is a BRAF-associated CNS tumor. In one embodiment, the BRAF-associated CNS tumor is a BRAF-associated primary brain tumor. In one embodiment, the primary brain tumor is a primary malignant brain tumor. In one embodiment, the primary brain tumor is a benign primary brain tumor. In one embodiment, the primary brain tumor has a class I mutation. In one embodiment, the primary brain tumor has a BRAF V600 mutation. In one embodiment, the primary brain tumor has a BRAF V600E or BRAF V600K mutation. In one embodiment, the primary brain tumor has a class II mutation. In one embodiment, the primary brain tumor has a class II mutation selected from G469A, G469R, G469V, K601E, K601N, K601T, L597Q and L597V. In one embodiment, the primary brain tumor has a G469A mutation. Primary brain tumors are tumors that begin in the brain or spine and are collectively known as gliomas. The term glioma is used to describe tumors that originate from glial cells present in the CNS. According to the QMS classification of brain tumors, gliomas are classified according to cellular activity and aggressiveness on a scale that includes grade I (benign CNS tumors) and grades II to IV (malignant CNS tumors): Grade I glioma (pilocytic astrocytoma): usually occurs in children in the cerebellum or brainstem, and occasionally in the cerebral hemispheres, and are slow growing. Grade I can occur in adults. Although they are benign (QMS grade I), the difficulty in curing this disease makes their growth malignant in a behavior with high morbidity rates (Rostami, Acta Neurochir (Wien). 2017; 159(11): 2217-2221 ). Grade II glioma (low-grade gliomas): includes astrocytoma, oligodendroglioma, and mixed oligoastrocytoma. Grade II gliomas usually appear in young adults (between 20 and 50 years old) and are most frequently found in the cerebral hemispheres. Due to the infiltrative nature of these tumors, recurrences may occur. Some grade II gliomas recur and evolve into more aggressive tumors (grade III or IV). Grade III glioma (malignant glioma): includes anaplastic astrocytoma, anaplastic oligodendroglioma, and mixed anaplastic oligoastrocytoma. Grade III tumors are aggressive, high-grade types of cancer and invade nearby brain tissue with tentacle-like projections, making them more difficult to remove surgically. Grade IV gliomas: includes glioblastoma multiforme (GBM) and gliosarcoma; (GBM) is a malignant glioma. GBM is the most aggressive and common primary brain tumor. Glioblastoma multiforme spreads rapidly and invades other parts of the brain, with tentacle-like projections, making it more difficult to remove surgically. Gliosarcoma is a malignant cancer and is defined as a glioblastoma consisting of gliomatous and sarcomatous components. In one embodiment, the BRAF-associated primary brain tumor is a glioma. In some embodiments, the BRAF-associated primary brain tumor is a glioma having a class I mutation. In some embodiments, the BRAF-associated primary brain tumor is a glioma having a class II mutation. Benign primary brain tumors can cause acute pain, permanent brain damage, and death, and in some cases, they can become malignant. Non-limiting examples of benign primary brain tumors include grade I gliomas, papillary craniopharyngiomas, meningioma (including rhabdoid meningioma), atypical teratoid / rhabdoid tumors, and dysembryoplastic neuroepithelial tumor (DNT), pilocytic astrocytoma, oligodendroglioma, mixed oligoastrocytoma, anaplastic astrocytoma, anaplastic oligodendroglioma, mixed anaplastic oligoastrocytoma, diffuse astrocytoma, ependymoma, a pleomorphic xanthoastrocytoma (PXA), a ganglioglioma, a gliosarcoma or an anaplastic ganglioglioma. In one embodiment, the BRAF-associated tumor is a benign primary brain tumor. In one embodiment, the BRAF-associated cancer is a cancer of the peripheral nervous system. In one embodiment, the cancer of the peripheral nervous system is neuroblastoma. In one embodiment, the cancer is a BRAF-associated cancer. Certain compounds of compounds of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or pharmaceutically acceptable salts thereof, were found to exhibit good penetration into the brain and / or CNS and / or exhibit low outflow. Such compounds are capable of crossing the BBB and may be useful for inhibiting a BRAF kinase in the brain and / or other CNS structures. Accordingly, certain compounds of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, described herein may also be used to treat associated tumors. to SNC BRAF. For example, treatment of a subject with a BRAF-associated CNS tumor may include administration (e.g., oral administration) of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, to the subject. In some embodiments, BRAF-associated CNS cancer has a BRAF V600 mutation. In some embodiments, the BRAF-associated CNS cancer has a BRAF V600E and / or V600K mutation. In some embodiments, BRAF-associated CNS cancer has a BRAF V600E mutation. In some embodiments, BRAF-associated CNS cancer has a BRAF V600K mutation. In some embodiments, the subject was previously treated with one or more other antineoplastic treatments, for example, an antineoplastic agent, surgery and / or radiation therapy, for example, as described below. In some embodiments, the subject is treated with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, in combination with one or more of other antineoplastic treatments, for example, an antineoplastic agent, surgery and / or radiation therapy, for example, as described below. In some embodiments, the subject is treated with one or more antineoplastic treatments, e.g., an antineoplastic agent, surgery and / or radiation therapy, following administration of a compound of Formula I, Formula I-A, Formula II, Formula III , Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, for example, as described hereinafter. In some embodiments of any of the methods described herein, the tumor is a BRAF-associated CNS tumor and the method includes administering a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In some embodiments, the BRAF-associated tumor is a CNS tumor. In some embodiments, the BRAF-associated CNS tumor is a malignant CNS tumor (CNS cancer). In some embodiments, the CNS malignant tumor is a metastatic CNS cancer. In some embodiments, the metastatic CNS cancer is metastatic melanoma. In some embodiments, the metastatic CNS cancer is colorectal cancer. In some embodiments, the metastatic CNS cancer is non-small cell lung cancer. In some embodiments, the metastatic CNS cancer is thyroid cancer. In some embodiments, the metastatic CNS cancer is metastatic ovarian cancer. In some embodiments, the BRAF-associated CNS tumor is LMD. In some embodiments, the LMD is intracranial. In some embodiments, the LMD is extracranial. In some embodiments, the LMD is metastatic melanoma. In some embodiments, LMD is colorectal cancer. In some embodiments, LMD is metastatic non-small cell lung cancer. In some embodiments, BRAF-associated CNS cancer is a primary brain tumor. In some embodiments, the primary brain tumor is a grade 2 glioma. In some embodiments, the primary brain tumor is a grade 3 glioma. In some embodiments, the primary brain tumor is a grade 4 glioma. In some embodiments, the BRAF-associated CNS tumor is a benign tumor. In some embodiments, the benign CNS tumor is a papillary craniopharyngioma, a meningioma (including rhabdoid meningioma), an atypical teratoid / rhabdoid tumor, or a dysembryoplastic neuroepithelial tumor (DNT). In some embodiments, the compound is selected from a compound of Examples 1-164 or a pharmaceutically acceptable salt thereof. The ability to determine whether a compound may be suitable for treating a CNS cancer can be determined, for example, by identifying whether the compound is a substrate of an efflux transporter and / or by measuring cell permeability and / or by measuring the ratio of free brain to free plasma, as described herein. In some embodiments, compounds of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or pharmaceutically acceptable salts thereof, exhibit high cell permeability. Methods for determining the permeability of a compound may be determined in accordance with the test described in Example B, and permeability coefficients are provided for compounds of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V in Table Bl. Certain compounds of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, exhibit a low efflux. In vitro methods are described to evaluate whether compounds are substrates for the efflux transporters P-glycoprotein (P-gp or multidrug resistance protein 1 (MDR1)) and breast cancer resistance protein (BCRP) in Example B, and efflux ratios of compounds of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V are provided in Table B2. In one embodiment, the compounds of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, have an efflux ratio <3 .5 when evaluated in cells expressing P-gp. In one embodiment, the compounds of Formula I, Formula ΙΑ, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, have a efflux ratio <3.5 when evaluated in cells expressing P-gp and an efflux ratio <5.5 when evaluated in cells expressing BCRP. In some embodiments, certain compounds of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, exhibit brain (unfixed) / brain ratios. medium to high (unfixed) plasma (i.e., medium to high brain / free plasma ratios). The ability of a compound to penetrate the BBB of a subject (e.g., a human) can be determined in a suitable animal model (e.g., a rodent, such as a mouse). For example, the ability of certain compounds of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V to penetrate the BBB in mice was determined by evaluating the concentration ratio in unfixed brain to unfixed plasma. fixed (C / free P) in mice, for example, as described in Example C, and the ratios of free brain to free plasma are provided in Table C. The highest ratios of free brain to free plasma or equal to 0.3 show a significant degree of penetration into the free CNS. Accordingly, in some embodiments, the methods of the present invention include methods of treating a BRAF-associated CNS cancer in a subject in need thereof. In one embodiment, the method includes administering a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, so that at least a portion of the compound of Formula I, Formula ΙΑ, Formula II, Formula III, Formula IV or Formula V penetrates the BBB, as demonstrated in a suitable animal model. In some embodiments, the total drug brain / plasma ratio is at least about 0.3 after administration (e.g., oral or intravenous administration) to a subject. It should be noted that the percentage of a compound that penetrates the BBB is calculated based on the area under the concentration-time curve for a given period of time (AUCo-t) in the brain compared to plasma. Consequently, the percentages represent a relationship of concentrations. That is, if (AUCo-24h) for a compound is 30 ng / ml in the brain and 70 ng / ml in plasma, then the percentage of the compound that penetrates the BBB is 30% (30 ng / ml in brain divided by the total concentration of (30 ng / ml + 70 ng / ml)) (i.e. a brain to plasma ratio of 0.30). In some embodiments, percentages are calculated based on the area under the concentration-time curve for the time period from t=0 (time of dose) to the last quantifiable concentration point, i.e., (AUCo-ultimate ). Mutations in the BRAF gene have been identified in malignant melanomas, papillary thyroid carcinomas, colorectal carcinomas, non-small cell lung carcinoma (NSCLC), and ovarian carcinomas and metastatic tumors from these, and in primary brain tumors (Davies et a! ., 2002). For example, BRAF mutations have been observed in numerous metastatic CNS tumors, including brain metastases from melanoma (Flaherty KT, etaL, Nat Rev Cancer (2012) 12(5):349-61), brain metastases from colorectal cancers. and brain metastases from non-small cell lung cancer (Berghoff, AS, Preusser M., Curr Opin Neurol (2014) 27(6):689696), papillary thyroid cancer (Kim, WW eta / ., J Otolaryngol Head Neck Surg. 2018; 47: 4) and ovarian cancer (Grisham RN., et al, Cancer. 2013;119:548-554). BRAF mutations have also been observed in primary malignant brain tumors, including grade IV gliomas, for example, glioblastomas and gliosarcomas, anaplastic astrocytomas (high-grade tumors), and QMS grade III anaplastic gangliogliomas (Berghoff, AS, Preusser M ., Curr Opin Neurol (2014) 27(6):689-696); Schindler et al. (Acta Neuropathol 121(3):397-405, 2011); Behling et al. (Diagn Pathol 11(1):55, 2016)), in pediatric and adult populations. BRAF mutations have also been observed in benign primary brain tumors, for example, in WHO grade II astrocytomas, WHO grade II pleomorphic xanthoastrocytomas (PXA), pleomorphic xanthoastrocytomas with anaplasia, pilocytic astrocytoma (PA), papillary craniopharyngiomas , gangliogliomas, astroblastomas, pilocytic astrocytomas, atypical teratoid / rhabdoid tumors, rhabdoid meningiomas (Berghoff, AS, Preusser M., Curr Opin Neurol (2014) 27(6):689-696; Schindler etal. (Acta Neuropathol 121(3) :397-405, 2011); (2):161-165, 2014; Dougherty etal., Neuro Oncol 12(7):621-630, 2010; 32(3):207-211, 2015; Myung etal / ., Transí Oncol 5(6):430-436, 2012; Schindler etal, Acta Neuropathol 121(3):397-405, 2011)), in pediatric populations and adults. BRAF mutations have also been detected in recurrent neuroblastomas (Eleveld, TF, etal., Nat Genet 47(8):864-871, 2015). Neuroblastoma is a pediatric tumor of the peripheral nervous system. Most subjects with neuroblastoma have tumors that initially respond to chemotherapy, but a large proportion of subjects will experience treatment-resistant recurrences. Accordingly, also provided herein is a method of treating a subject diagnosed with, or identified as having, a BRAF-associated tumor, for example, any of the exemplary BRAF-associated tumors disclosed herein, comprising administering to the subject a therapeutically effective amount of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof as defined herein. In some embodiments, the subject who has been identified or diagnosed with a BRAF-associated tumor by using a regulatory-approved test or assay, for example, approved by the FDA, to identify a BRAF mutation in a subject or a biopsy sample from the subject or by performing any of the non-limiting examples of assays described herein. In some embodiments, the test or assay is provided as a kit. In one embodiment, the BRAF-associated tumor may be a cancer that has one or more BRAF class I mutations (e.g., V600E and / or V600K). In one embodiment, the BRAF-associated tumor may be a cancer that has one or more class II mutations (e.g., G469A). In some embodiments, a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V is a compound selected from Examples 1-164 or a pharmaceutically acceptable salt thereof. In some embodiments, the BRAF-associated tumor is a malignant BRAF-associated tumor (i.e., a BRAF-associated cancer). In some embodiments, the BRAF-associated cancer is a BRAF-associated CNS cancer. In some embodiments, the BRAF-associated CNS cancer is a BRAF-associated metastatic cancer. In some embodiments, the BRAF-associated metastatic cancer is metastatic melanoma. In some embodiments, the BRAF-associated metastatic cancer is metastatic colorectal cancer. In some embodiments, the BRAF-associated metastatic cancer is metastatic non-small cell lung cancer. In some embodiments, the BRAF-associated metastatic cancer is metastatic thyroid cancer. In some embodiments, the BRAF-associated metastatic cancer is metastatic ovarian cancer. In some embodiments, the BRAF-associated metastatic cancer is intracranial LMD or extracranial LMD. In some embodiments, BRAF-associated CNS cancer is a primary brain tumor. In some embodiments, the BRAF-associated tumor is a benign CNS tumor. In some embodiments, the cancer is selected from lung cancer (e.g., non-small cell lung cancer and small cell lung cancer), melanoma, colorectal cancer, breast cancer, pancreatic cancer, thyroid cancer. , prostate cancer, adenoid cystic carcinoma, appendiceal cancer, small intestine cancer, head and neck squamous cell carcinoma, angiosarcoma and CNS tumors. In some embodiments, the compound is selected from a compound of Examples 1-164 or a pharmaceutically acceptable salt thereof. In some embodiments, the subject is an adult subject. In some embodiments, the subject is a pediatric subject. Also provided are methods for treating a tumor in a subject in need thereof, comprising: (a) detecting a BRAF-associated tumor in the subject; and (b) administering to the subject a therapeutically effective amount of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof or a pharmaceutical composition of this. In some embodiments of these methods, the tumor is a benign BRAF-associated tumor. In some embodiments of these methods, the tumor is a malignant BRAF-associated tumor. In some embodiments of these methods, the tumor is a BRAF-associated malignant tumor (e.g., any of the malignant BRAF-associated tumors described herein), and the method further includes administering to the subject one or more additional antineoplastic treatments. , for example, surgery (for example, at least partial resection of the tumor) and / or radiotherapy and / or an antineoplastic agent. In some embodiments of these methods, the tumor is a benign BRAF-associated tumor, e.g., a benign BRAF-associated CNS tumor, and the method further includes administering to the subject one or more additional antineoplastic treatments, e.g., surgery. (for example, at least partial resection of the tumor) and / or radiotherapy and / or an antineoplastic agent. In some embodiments, the subject is determined to have a BRAF-associated tumor by using a regulatory-approved test or assay, for example, approved by the FDA, to identify a BRAF mutation in a subject or sample. biopsy of the subject (for example, a liquid or tissue biopsy) or by performing any of the non-limiting examples of assays described herein. In some embodiments, the test or assay is provided as a kit. In some embodiments, the BRAF-associated tumor is a malignant BRAF-associated tumor (i.e., a BRAF-associated cancer). In some embodiments, the BRAF-associated cancer is a BRAF-associated CNS cancer. In some embodiments, the BRAF-associated CNS cancer is a BRAF-associated metastatic cancer. In some embodiments, the BRAF-associated metastatic cancer is metastatic melanoma. In some embodiments, the BRAF-associated metastatic cancer is metastatic colorectal cancer. In some embodiments, the BRAF-associated metastatic cancer is metastatic non-small cell lung cancer. In some embodiments, the BRAF-associated metastatic cancer is metastatic thyroid cancer. In some embodiments, the BRAF-associated metastatic cancer is metastatic ovarian cancer. In some embodiments, the BRAF-associated metastatic cancer is intracranial LMD or extracranial LMD. In some embodiments, BRAF-associated CNS cancer is a primary brain tumor. In some embodiments, the BRAF-associated tumor is a benign CNS tumor. In some embodiments, the cancer is selected from lung cancer (e.g., non-small cell lung cancer and small cell lung cancer), melanoma, colorectal cancer, breast cancer, pancreatic cancer, thyroid cancer. , prostate cancer, adenoid cystic carcinoma, appendiceal cancer, small intestine cancer, head and neck squamous cell carcinoma, angiosarcoma and CNS tumors. In some embodiments, the compound is selected from a compound of Examples 1-164 or a pharmaceutically acceptable salt thereof. In some embodiments, the subject is an adult subject. In some embodiments, the subject is a pediatric subject. Also provided are methods of treating a subject having a BRAF-associated tumor that include performing an assay on a sample obtained from the subject to determine that the subject has a tumor having a BRAF mutation, and administering a therapeutically effective amount of a compound. of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof or a pharmaceutical composition thereof to the subject having a BRAF mutation, as determined . In some embodiments of these methods, the BRAF-associated tumor is a BRAF-associated malignant tumor (i.e., a BRAF-associated cancer), and the method further includes administering to the subject one or more other antineoplastic treatments, e.g. , surgery (for example, at least partial resection of a tumor) and / or radiation therapy and / or treatment with an antineoplastic agent. In some embodiments of these methods, the subject was previously treated with another antineoplastic treatment, for example, surgery (e.g., at least partial resection of a tumor) and / or radiation therapy and / or treatment with an antineoplastic agent. In some embodiments, the subject is a subject suspected of having a BRAF-associated tumor, a subject who exhibits one or more symptoms of a BRAF-associated tumor, or a subject who is at high risk of developing a BRAF-associated tumor. to BRAF. In some embodiments, the assay uses next generation sequencing, pyrosequencing, immunohistochemistry, or breakage FISH analysis. In some embodiments, the assay is a regulatory approved assay, for example, FDA approved kit. In some embodiments, the assay is a liquid biopsy. In some embodiments, the biopsy is a tissue biopsy. In some embodiments, the cancer is a CNS cancer and the biopsy is a liquid biopsy (e.g., CSF). In some embodiments, the cancer is a CNS cancer and the biopsy is a tissue biopsy (e.g., a tumor sample obtained during traditional surgery or a stereotactic needle biopsy, e.g., a stereotactic needle biopsy guided by computed tomography or magnetic resonance imaging). Additional non-limiting assays that may be used in these methods are described herein. Additional tests are also known in the art. In some embodiments, the BRAF-associated tumor is a malignant BRAF-associated tumor (i.e., a BRAF-associated cancer). In some embodiments, the BRAF-associated cancer is a BRAF-associated CNS cancer. In some embodiments, the BRAF-associated CNS cancer is a BRAF-associated metastatic cancer. In some embodiments, the BRAF-associated metastatic cancer is metastatic melanoma. In some embodiments, the BRAF-associated metastatic cancer is metastatic colorectal cancer. In some embodiments, the BRAF-associated metastatic cancer is metastatic non-small cell lung cancer. In some embodiments, the BRAF-associated metastatic cancer is metastatic thyroid cancer. In some embodiments, the BRAF-associated metastatic cancer is metastatic ovarian cancer. In some embodiments, the BRAF-associated metastatic cancer is intracranial LMD or extracranial LMD. In some embodiments, BRAF-associated CNS cancer is a primary brain tumor. In some embodiments, the BRAF-associated tumor is a benign CNS tumor. In some embodiments, the cancer is selected from lung cancer (e.g., non-small cell lung cancer and small cell lung cancer), melanoma, colorectal cancer, breast cancer, pancreatic cancer, thyroid cancer. , prostate cancer, adenoid cystic carcinoma, appendiceal cancer, small intestine cancer, head and neck squamous cell carcinoma, angiosarcoma and CNS tumors. In some embodiments, the subject is an adult subject. In some embodiments, the subject is a pediatric subject. Also provided is a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, for use in the treatment of a BRAF-associated tumor in a subject identified or diagnosed as having a BRAF-associated tumor by a step of performing an assay (e.g., an in vitro assay) on a sample obtained from the subject to determine that the subject has a BRAF mutation, where the presence of a BRAF mutation identifies that the subject has a BRAF-associated tumor. Also provided is the use of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for treating a BRAF-associated tumor in a subject identified or diagnosed as having a BRAF-associated tumor by a step of performing an assay on a sample obtained from the subject to determine whether the subject has a BRAF mutation that identifies the subject as having an associated tumor to BRAF. Some embodiments of any of the methods or uses described herein further include recording in the subject's medical record (e.g., a computer-readable medium) that the subject is determined to have a BRAF mutation by performing the assay. and that the subject should be administered a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof or a pharmaceutical composition thereof. In some embodiments, the assay uses next generation sequencing, pyrosequencing, immunohistochemistry, or breakage FISH analysis. In some embodiments, the assay is a regulatory approved assay, for example, FDA approved kit. In some embodiments, the assay is a liquid biopsy. In some embodiments, the BRAF-associated tumor is a malignant BRAF-associated tumor (i.e., a BRAF-associated cancer). In some embodiments, the BRAF-associated cancer is a BRAF-associated CNS cancer. In some embodiments, the BRAF-associated CNS cancer is a BRAF-associated metastatic cancer. In some embodiments, the BRAF-associated metastatic cancer is metastatic melanoma. In some embodiments, the BRAF-associated metastatic cancer is metastatic colorectal cancer. In some embodiments, the BRAF-associated metastatic cancer is metastatic non-small cell lung cancer. In some embodiments, the BRAF-associated metastatic cancer is metastatic thyroid cancer. In some embodiments, the BRAF-associated metastatic cancer is metastatic ovarian cancer. In some embodiments, the BRAF-associated metastatic cancer is intracranial LMD or extracranial LMD. In some embodiments, BRAF-associated CNS cancer is a primary brain tumor. In some embodiments, the BRAF-associated tumor is a benign CNS tumor. In some embodiments, the cancer is selected from lung cancer (e.g., non-small cell lung cancer and small cell lung cancer), melanoma, colorectal cancer, breast cancer, pancreatic cancer, thyroid cancer. , prostate cancer, adenoid cystic carcinoma, appendiceal cancer, small intestine cancer, head and neck squamous cell carcinoma, angiosarcoma and CNS tumors. In some embodiments, the subject is an adult subject. In some embodiments, the subject is a pediatric subject. Also provided is a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, for use in the treatment of a BRAF-associated tumor in a subject in need or a subject identified or diagnosed as having a BRAF-associated tumor. Also provided is the use of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for treating a BRAF-associated tumor in a subject identified or diagnosed as having a BRAF-associated tumor. In some embodiments, a subject is identified or diagnosed as having a BRAF-associated tumor with a regulatory-approved kit, e.g., FDA-approved, to identify a BRAF mutation in a subject or biopsy specimen. of the subject. In some embodiments, the BRAF-associated tumor is a malignant BRAF-associated tumor (i.e., a BRAF-associated cancer). In some embodiments, the BRAF-associated cancer is a BRAF-associated CNS cancer. In some embodiments, the BRAF-associated CNS cancer is a BRAF-associated metastatic cancer. In some embodiments, the BRAF-associated metastatic cancer is metastatic melanoma. In some embodiments, the BRAF-associated metastatic cancer is metastatic colorectal cancer. In some embodiments, the BRAF-associated metastatic cancer is metastatic non-small cell lung cancer. In some embodiments, the BRAF-associated metastatic cancer is metastatic thyroid cancer. In some embodiments, the BRAF-associated metastatic cancer is metastatic ovarian cancer. In some embodiments, the BRAF-associated metastatic cancer is intracranial LMD or extracranial LMD. In some embodiments, BRAF-associated CNS cancer is a primary brain tumor. In some embodiments, the BRAF-associated tumor is a benign CNS tumor. In some embodiments, the cancer is selected from lung cancer (e.g., non-small cell lung cancer and small cell lung cancer), melanoma, colorectal cancer, breast cancer, pancreatic cancer, thyroid cancer. , prostate cancer, adenoid cystic carcinoma, appendiceal cancer, small intestine cancer, head and neck squamous cell carcinoma, angiosarcoma and CNS tumors. In some embodiments, the subject is an adult subject. In some embodiments, the subject is a pediatric subject. In some embodiments of any of the methods or uses described herein, an assay used to determine whether the subject has a BRAF mutation using a sample from a subject may include, for example, next generation sequencing, immunohistochemistry, fluorescence microscopy, breakage FISH analysis, Southern blotting, Western blotting, FACS analysis, Northern blotting, and PCR amplification (e.g., RT-PCR and quantitative real-time RT-PCR). As is known in the art, assays are generally performed, for example, with at least one labeled nucleic acid probe or at least one labeled antibody or an antigen-binding fragment thereof. The assays may use other detection methods known in the art to detect a BRAF mutation. In some embodiments, the sample is a biological sample or a biopsy sample (e.g., a paraffin-embedded biopsy sample) from the subject. In some embodiments, the subject is a subject suspected of having a BRAF-associated tumor, a subject who has one or more symptoms of a BRAF-associated tumor, and / or a subject who has an increased risk of developing a BRAF-associated tumor. BRAF-associated tumor. In some embodiments, the biopsy is a tumor biopsy (e.g., a tumor sample obtained during traditional surgery or a stereotactic needle biopsy, e.g., a stereotactic needle biopsy guided by CT or MRI). Tissue biopsy methods can be used to detect total tumor mass and / or BRAF mutation. In some embodiments, the BRAF mutation can be identified with a liquid biopsy (also called fluid biopsy or fluid phase biopsy). See, for example, Karachialiou et al, Real-time liquid biopsies become a reality in cancer treatment, Ann. I passed. Med., 3(3):36, 2016. Liquid biopsy methods can be used to detect total tumor mass and / or BRAF mutation. Liquid biopsies can be performed on biological samples obtained relatively easily from a subject (e.g., by a simple blood draw) and are generally less invasive than traditional methods used to detect tumor mass and / or BRAF mutation. In some embodiments, liquid biopsies can be used to detect the presence of a BRAF mutation at an earlier stage than traditional methods. In some embodiments, the biological sample to be used in a liquid biopsy may include CSF, blood, plasma, urine, saliva, sputum, bronchoalveolar lavage, bile, lymphatic fluid, cystic fluid, feces, ascites, and combinations of these. In some embodiments, a liquid biopsy can be used to detect circulating tumor cells (CTCs). In some embodiments, a liquid biopsy can be used to detect cell-free DNA. In some embodiments, the cell-free DNA detected with a liquid biopsy is circulating tumor DNA (ctDNA) derived from tumor cells. ctDNA analysis (e.g., with sensitive detection techniques such as, but not limited to, next-generation sequencing (NGS), traditional PCR, digital PCR, or microarray analysis) can be used to identify a BRAF mutation. In some embodiments, a BRAF mutation identified with a liquid biopsy is also present in a cancer cell that is present in the subject (e.g., in a tumor). In some embodiments, either type of BRAF mutation can be detected with a liquid biopsy. In some embodiments, a genetic mutation identified by a liquid biopsy may be used to identify that the subject is a candidate for a particular treatment. For example, detection of a BRAF mutation in the subject may indicate that the subject will respond to a treatment that includes administration of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt of this. Tumor mass, also called tumor burden, refers to the total amount of tumor material distributed throughout the body. Tumor mass refers to the total number of cancer cells, or the total size of tumors, throughout the body, including the lymph nodes and bone marrow. Tumor mass can be determined by various methods known in the art, such as, for example, measuring the dimensions of tumors after removal from the subject, for example, with calipers, or, when in the body, with imaging techniques. , for example, magnetic resonance imaging (MRI), computed tomography (CT), multidetector computed tomography (MDCT), positron emission tomography (PET), X-ray, ultrasound, or bone scan. The term tumor size or tumor size refers to the total size of the tumor, which can be measured as the length and width of a tumor. Tumor size can be determined with various methods known in the art, such as, for example, measuring the dimensions of the tumors after removing them from the subject, for example, with calipers, or, when in the body, with imaging techniques. , for example, MRI, bone scan, ultrasound or CT scan. Liquid biopsies may be performed at multiple time points during making a diagnosis, performing monitoring, and / or performing treatment to determine one or more clinically relevant parameters, including, but not limited to, disease progression or effectiveness of a treatment, after administering a treatment to the subject. For example, a first liquid biopsy may be performed at a first time point and a second iviA / a / zuzz / u i o i u □ liquid biopsy may be performed at a second time point during making a diagnosis, performing monitoring, and / or or performing a treatment. In some embodiments, the first time point may be a time point before a subject is diagnosed with a disease (e.g., when the subject is healthy), and the second time point may be a time point after that the subject has developed the disease (for example, the second time point can be used to diagnose the subject with the disease). In some embodiments, the first time point may be a time point before a subject is diagnosed with a disease (e.g., when the subject is healthy), after which the subject is monitored, and the second time point Time can be a time point after monitoring the subject. In some embodiments, the first time point may be a time point after a subject is diagnosed with a disease, after which a treatment is administered to the subject, and the second time point may be a time point after that the treatment is administered; In such cases, the second time point can be used to assess the efficacy of the treatment (for example, whether genetic mutations detected at the first time point are reduced in abundance or undetectable). In some embodiments, a treatment to be administered to a subject may include a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt. of this. In one embodiment, a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, may be used alone or in combination with a or more different forms of treatment to treat a subject with a malignant tumor. For example, a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, may also be used in combination with one or more antineoplastic treatments. additional, for example, surgery, radiotherapy and / or an antineoplastic agent that works with the same or a different mechanism of action. In one embodiment, treating a subject having a BRAF-associated malignant tumor with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a commercially acceptable salt pharmaceutical view thereof, in combination with one or more additional treatments, for example, surgery, radiotherapy and / or an antineoplastic agent, may have greater therapeutic efficacy than treatment of the same subject or a similar subject with a compound of Formula I , Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt, as monotherapy. Accordingly, in one embodiment, methods are provided herein for treating a subject having a BRAF-associated tumor (e.g., any of the BRAF-associated tumors described herein) including: administering to the subject (i ) a therapeutically effective amount of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, as a monotherapy, or (i) a therapeutically effective amount of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, in combination with one or more additional antineoplastic treatments. In one embodiment, provided herein is a method of treating a subject having a BRAF-associated tumor (e.g., any of the BRAF-associated tumors described herein) comprising administering a therapeutically effective amount of a compound. of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, over a period of time, wherein the subject is administered a second antineoplastic treatment during said period of time. In one embodiment, the second antineoplastic treatment is a second antineoplastic agent. Also provided herein is a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, for use in combination with additional antineoplastic treatment. . Also provided herein is an additional antineoplastic treatment for use in combination with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. Also provided herein is a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, for use in the treatment of an associated tumor to BRAF by coadministration with additional antineoplastic therapy. Also provided herein is an additional antineoplastic treatment for use in the treatment of a BRAF-associated tumor by coadministration with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a salt acceptable from its pharmaceutical point of view. In some embodiments, the subject is administered one or more antineoplastic treatments other than a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt. thereof, prior to administration of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In some embodiments, the one or more antineoplastic treatments are selected from surgery, radiation therapy and / or an antineoplastic agent that works with the same or a different mechanism of action. For example, in some embodiments, a subject in need may undergo at least partial resection of the tumor prior to administration of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV, or Formula V. , or a pharmaceutically acceptable salt thereof. In some embodiments, treatment with at least partial resection of the tumor that reduces the size of the tumor (e.g., tumor mass) occurs prior to administration of one or more doses of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In some embodiments, a subject in need thereof may undergo radiation therapy prior to administration of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a commercially acceptable salt. pharmaceutical view of this. In some embodiments, a subject in need thereof may receive treatment with one or more antineoplastic agents other than a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or an acceptable salt thereof. pharmaceutical point of view thereof, prior to the administration of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In some embodiments, a subject has a cancer that resists or does not tolerate prior treatment. Accordingly, in some embodiments, methods are provided herein for treating a subject having a BRAF-associated tumor, comprising (i) administering one or more antineoplastic treatments to said subject over a period of time, and i) after (i), administering (a) a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, as monotherapy or (b) a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, in combination with one or more additional antineoplastic treatments. In some embodiments, a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, may be administered prior to administration of one or more antineoplastic treatments (for example, surgery, radiation therapy and / or an antineoplastic agent that works with the same or a different mechanism of action) to treat a subject who has the tumor. For example, in some embodiments, a subject in need may undergo at least partial resection of the tumor after administration of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V , or a pharmaceutically acceptable salt thereof. In some embodiments, a subject in need thereof may undergo radiation therapy following administration of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a commercially acceptable salt. pharmaceutical view of this. In some embodiments, a subject in need thereof may be treated with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, prior to the administration of a compound of one or more antineoplastic agents other than a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In one embodiment, the compound of Formula I is a compound selected from Examples 1164 or a pharmaceutically acceptable salt thereof. Accordingly, in some embodiments, methods are provided herein for treating a subject having a BRAF-associated tumor, comprising (i) administering Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, for a period of time, and (i) after such period of time, the administration of one or more antineoplastic treatments. For example, a subject in need may receive one or more doses of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, for a period of time and then undergo at least partial resection of the tumor. In some embodiments, treatment with one or more doses of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, reduces the size of the tumor (e.g., tumor mass) before at least partial resection of the tumor. In one embodiment, the compound of Formula I is a compound selected from Examples 1-164 or a pharmaceutically acceptable salt thereof. In some embodiments of any of the methods described above, the additional antineoplastic treatment is surgery, radiation therapy and / or an antineoplastic agent that works with the same or a different mechanism of action. Non-limiting examples of additional antineoplastic agents that may be used in combination with a compound of Formula I, II or III, or a pharmaceutically acceptable salt thereof, according to any of the methods described above include, but are not limited to others, MEK inhibitors, BRAF inhibitors (for example, BRAF inhibitors other than a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V), EGFR inhibitors, HER2 inhibitors and / or HER3, Axl inhibitors, PI3K inhibitors and SOS1 inhibitors), signal transduction pathway inhibitors, checkpoint inhibitors, apoptotic pathway modulators, cytotoxic chemotherapeutic agents, angiogenesis-targeted therapies and system-targeted agents immune, including immunotherapy. In one embodiment, the antineoplastic agent which may be used in combination with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, according to any of the methods described above is a targeted therapeutic agent. A targeted therapeutic agent, as used herein, refers to a molecule that blocks the growth of cancer cells by interfering with specific target molecules necessary for carcinogenesis and tumor growth, rather than simply interfering with all cell division. rapid (for example, with traditional cytotoxic chemotherapy), and includes, among others, therapeutic agents targeting the receptor tyrosine kinase, inhibitors of the signal transduction pathway (for example, inhibitors of the Ras-Raf-MEK-ERK pathway, inhibitors of the PI3K-Akt-mTOR-S6K pathway (PI3K inhibitors)), and modulators of the apoptotic pathway. In some embodiments, the antineoplastic agent which may be used in combination with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, according to any of the methods described above is a MEK inhibitor. In one embodiment, the MEK inhibitor is binimetinib, trametinib, cobimetinib, selumetinib, pimasertib, refametinib, mirdametinib, 2-(2chloro-4-iodophenylamino)-N-(cyclopropylmethox)-3, 4-difluorobenzamide (CI-1040), 3-[2(R),3d¡hydroxy¡propyl]-6-fluoro-5-(2-fluoro-4-iodophen¡lamino)-8- methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione (TAK-733), or a pharmaceutically acceptable salt thereof. Additional examples of MEK inhibitors include the compounds disclosed in WO 03 / 077914, WO 2005 / 023759, WO 2005 / 051301, US 7,517,994, US 7,732,616, WO 2005 / 051906, WO 2005 / 051302, WO 2005 / 0513 00 and WO 2007 / 044084. In some embodiments, the MEK inhibitor is binimetinib, or a pharmaceutically acceptable salt thereof. In some embodiments, the antineoplastic agent which may be used in combination with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, according to any of the methods described above is another BRAF inhibitor other than a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V. Non-limiting examples of other BRAF inhibitors include encorafenib, dabrafenib, vemurafenib, N-[3-(5-chloro-lH-pyrrolo[2,3b]pyridin-3-ylcarbon¡l)-2,4-difluorophen¡l]propan-l-sulfonamide (PLX4720), (3R)-N-(3-[[5-(2cycloprop¡lpyrimidin-5-yl)-lH-pyrrolo[2,3-b]pyridín-3-yl]carbonyl]-2, 4-difluorophenyl)-3-fluoropyrrolidine-lsulfonamide (PLX8394), and pharmaceutically acceptable salts thereof, and the compounds disclosed in International Application No. PCT / IB2020 / 055992, published on December 30 of 2020 as PCTN publication No. WO 2020 / 261156 Al, including, for example, a compound selected from: / V-(3-((3,5-dimethyl-4-oxo-3,4-dihydroqunazolin-6-yl)amino)-2,4-difluorophenyl )propan-lsulfonamide; / V-(2-chloro-3-((3,5-dimethyl-4-oxo-3,4-dihydroquinazolin-6-l)amino)phenyl )-3fluoropropan-l-sulfonamide; / V-(2-chloro-3-((3,5-dimethyl-4-oxo-3,4-dihydroqunazolin-6-l)amino)- 4,582 difluorophenyl)propan-l-sulfonamide; A / -(2-chloro-3-((3,5-dimethyl-4-oxo-3,4-dihydroquinazolin-6-l)amino)- 4fluorophenyl)propan-l-sulfonamide; / V-(2-chloro-3-((3,5-dimethyl-4-oxo-3,4-dihydroqunazoln-6-¡l)amino)-4- fluorophenyl)-3fluoropropan-l-sulfonamide; A / -(2-chloro-4-fluoro-3-((5-methyl-3-(methyl-d3)-4-oxo-3,4-dihydroquinazolin-6-l )amino)phenyl)-3-fluoropropan-l-sulfonamide; N-{2-chloro-3-[(3,5-dimethyl-4-oxo-3,4-dihydroquinazolin-6-¡l)oxy]-4-fluorophenyl}propan1-sulfonamide; N-(3-chloro-4-((3,5-dimethyl-4-oxo-3,4-dihydroqunazolin-6-¡l)ox¡)-5- fluorop¡ridín-2yl)propan-l-sulfonamide; and N-{2-chloro-3-[(3,5-dimethyl-4-oxo-3,4-d¡hydroquinazolin-6-¡l)oxy]-4-fluorophen¡l}-3fluoropropan-l-sulfonamide; or a pharmaceutically acceptable salt thereof. In one embodiment, the BRAF inhibitor is encorafenib or a pharmaceutically acceptable salt thereof. In one embodiment, the BRAF inhibitor is / V-(2-chloro-3-((3,5-dimethyl-4-oxo-3,4dihydroquinazolin-6-¡l)amino) -4-fluorophenyl)-3-fluoropropan-l-sulfonamide or a pharmaceutically acceptable salt thereof. Additional examples of BRAF inhibitors are known in the art. In some embodiments, the antineoplastic agent which may be used in combination with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, according to any of the methods described above is an EGFR inhibitor. Non-limiting examples of EGFR inhibitors include cetuximab (Erbitux®), panitumumab (Vectibix®), osimertinib (merelectinib, Tagrisso®), erlotinib (Tarceva®), gefitinib (Iressa®), necitumumab (Portrazza™), neratinib (Nerlynx ®), lapatinib (Tykerb®), vandetanib (Caprelsa®), brigatinib (Alunbrig®) and the EGFR inhibitors disclosed in PCT Publications No. WO 2019 / 071351 and WO 2017 / 117680, which are incorporated herein by reference in its entirety. Additional examples of EGFR inhibitors are known in the art. In one embodiment, the EGFR inhibitor is cetuximab. In some embodiments, the antineoplastic agent which may be used in combination with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, according to any of the methods described above is a HER2 and / or HER3 inhibitor. Non-limiting examples of HER2 and / or HER3 inhibitors include lapatinib, canertinib, (E)-2-methox¡-N-(3-(4-(3-methyl-4-(6met¡lp¡r¡ d¡n-3-¡lox¡)phen¡lano)quinazo¡n-6-¡l)allyl)acetam¡de (CP-724714), sapitinib, 7-[[4-[(3 ινΐΛ / a / zuzz / u i o i u □ et¡nylphenyl)am¡no]-7-methoxy-6-quinazo¡n¡l]ox¡]-N-hydroxy¡-heptanam¡de (CUDC-101), mubritinib, 6- [4[(4-eth¡lp¡perazin-l-yl)met¡l]phen¡l]-N-[(lR)-l-phen¡let¡l]-7H-pyrrolo[2,3 -d]pyrám¡din-4-amine (AEE788), irbinitinib (tucatinib), poziotinib, N-[4-[l-[4-(4-acet¡l-l-p¡peraz¡n¡l)cyclohex ¡l]-4-am¡no-3-p¡razolo[3,4d]pyrimid¡n¡l]-2-methoxy¡phenyl]-l-methyl¡l-2-indolecarboxamide (KIN001-111), 7 -cyclopentyl-5-(4-phenoxyphenyl)7H-pyrrolo[2,3-d]p¡r¡m¡d¡n-4-ylam¡na (KIN001-051), 6,7-dimethoxy¡-N- (4-phenoxyphenyl)quinazolin-4-amine (KIN001-30), dasatinib and bosutinib. In some embodiments, the antineoplastic agent which may be used in combination with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, according to any of the methods described above is an Axl inhibitor. Non-limiting examples of Axl inhibitors include bemcentinib, YW327.6S2 (monoclonal antibody), GL2I.T (decoy receptor), 2-(5-chloro2-(4-((4-methylpiperazin-l-¡l)met¡ l)phenylamino)pyrimidin-4-ylamino)-N,N-dimethylbenzenesulfonamide (TP0903), 3-[2-[[3-fluoro-4-(4-methyl-l-p¡ peraz¡n¡l)phen¡l]am¡no]-5-met¡l-7Hp¡rrolo[2,3-d]p¡r¡m¡din-4-¡l]benzenacetonitrile (SGI-7079) , gilteritinib, bosutinib, cabozantinib, sunitinib, foretinib, amuvatinib, glesatinib, N-(4-((2-am¡no-3-chloropyridin-4-¡l)ox¡)-3-fluorophenyl)-4-ethoxy- l-(4-fluorophenyl)-2-oxo-l,2-dihydropyridine-3-carboxamide (BMS777607), merestinib, (Z)-3-((3-((4-(morpholinomethyl)-lH-pyrrole-2yl )methylene)-2-oxoindolin-5-¡l)methyl)thiazolidín-2,4-dione (S49076) and (R)-N-(3-fluoro-4-((3-( (lhydroxypropan-2-yl)amino)-lH-pyrazolo[3,4-b]pyridin-4-yl)oxy)phenyl)-3-(4-fluorophenyl) -l-isopropyl-2,4dioxo-l,2,3,4-tetrahydropyrimidine-5-carboxamide. In some embodiments, the antineoplastic agent which may be used in combination with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, according to any of the methods described above is an SOS1 inhibitor. Non-limiting examples of SOS1 inhibitors include those disclosed in PCT Publication No. WO 2018 / 115380, which is incorporated herein by reference in its entirety. In some embodiments, the antineoplastic agent which may be used in combination with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, according to any of the methods described above is a PI3K inhibitor. Non-limiting examples include buparlisib (BKM120), alpelisib (BYL719), samotolisib (LY3023414), 8-[(lR)-l-[(3,5difluorophen¡l)amino]ethyl]-N,N-dimethyl- 2-(morpholin-4-yl)-4-oxo-4H-chromen-6-carboxamide (AZD8186), tenalisib (RP6530), voxtalisib hydrochloride (SAR-245409), gedatolisib (PF-05212384), panulisib ( P7170), taselisib (GDC-0032), trans-2-amino-8-[4-(2-hydroxyethoxy)cyclohexyl]-6-(6-methoxypyridin-3-yl)-4methylpyridide [2,3-d]pyrimidin-7(8H)-one (PF-04691502), duvelisib (ABBV-954), N2-[4-oxo-4[4-(4-oxo- 8-phen¡l-4H-l-benzop¡ran-2-¡l)morpholin-4-io-4-¡lmethox¡]butíryl]-L-arg¡n¡l-gl¡c¡l-L- aspartyl-L ΜΛ / a / ZUZZ / U 1 0 / U J serine (SF-1126), pictilisib (GDC-0941), 2-methyl-l-[2-methyl-3-(trifluoromethyl)benzyl] acid -6-(morpholin4-¡l)-lH-benzimidazole-4-carboxylic acid (GSK2636771), idelalisib (GS-1101), thresholdisib tosylate (TGR1202), pictilisib (GDC-0941), copanlisib hydrochloride (BAY 84-1236 ), dactolisib (BEZ-235), l-(4-[5[5-amino-6-(5-tert-butyl-l,3,4-oxadiazol-2-¡l)pyrazin-2-¡l] -l-ethyl-lH-l,2,4-triazol-3-yl]piper¡din-l-yl)-3hydroxypropan-l-one (AZD-8835), 5-[6,6-dimethyl-4- (morpholin-4-yl)-8,9-dihydro-6H-[l,4]oxazino[4,3e]purin-2-yl]pyrimidin-2-amine (GDC-0084) everolimus, rapamycin , perifosine, sirolimus and temsirolimus. In some embodiments, the antineoplastic agent which may be used in combination with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, according to any of the methods described above is an immunotherapy. The term immunotherapy refers to an agent that modulates the immune system. In some embodiments, an immunotherapy may increase the expression and / or activity of an immune system regulator. In some embodiments, an immunotherapy may decrease the expression and / or activity of an immune system regulator. In some embodiments, an immunotherapy can recruit and / or enhance the activity of an immune cell. In some embodiments, immunotherapy which may be used in combination with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, of according to any of the methods described above is a treatment with antibodies (for example, a monoclonal antibody, an antibody conjugate). In some embodiments, the antibody treatment is bevacizumab (Mvasti™, Avastin®), trastuzumab (Herceptin®), avelumab (Bavencio®), rituximab (MabThera™, Rituxan®), edrecolomab (Panorex), daratumuab (Darzalex® ), olaratumab (Lartruvo™), ofatumumab (Arzerra®), alemtuzumab (Campath®), cetuximab (Erbitux®), oregovomab, pembrolizumab (Keytruda®), dinutiximab (Unituxin®), obinutuzumab (Gazyva®), tremelimumab (CP675, 206), ramucirumab (Cyramza®), ublituximab (TG-1101), panitumumab (Vectibix®), elotuzumab (Empliciti™), necitumumab (Portrazza™), cirmtuzumab (UC-961), ibritumomab (Zevalin®), isatuximab (SAR650984 ), nimotuzumab, fresolimumab (GC1008), lirilumab (INN), mogamulizumab (Poteligeo®), ficlatuzumab (AV-299), denosumab (Xgeva®), ganitumab, urelumab, pidilizumab, amatuximab, blinatumomab (AMG103; Blincyto®), or midostaurin (Rydapt). In some embodiments, immunotherapy which may be used in combination with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, of according to any of the methods described above is an antibody-drug conjugate. In some embodiments, the antibody-drug conjugate is gemtuzumab ozogamicin (Mylotarg™), inotuzumab ozogamicin (Besponsa®), brentuximab vedotin (Adcetris®), ado-trastuzumab emtansine (TDM-1; Kadcyla®), mirvetuximab soravtansine (IMGN853 ) or anetumab ravtansine. In some embodiments, immunotherapy which may be used in combination with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, of according to any of the methods described above includes a toxin. In some embodiments, the immunotherapy is denileukin diftitox (Ontak®). In some embodiments, immunotherapy which may be used in combination with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, of according to any of the methods described above is a cytokine treatment. In some embodiments, the cytokine treatment is a treatment with interleukin 2 (IL-2), a treatment with interferon alpha (IFNa), a treatment with granulocyte colony stimulating factor (G-CSF), a treatment with interleukin 12 (IL-12), a treatment with interleukin 15 (IL-15), a treatment with interleukin 7 (IL-7), or a treatment with erythropoietin-alpha (EPO). In some embodiments, the IL-2 treatment is aldesleukin (Proleukin®). In some embodiments, the IFNa treatment is IntronA® (Roferon-A®). In some embodiments, the G-CSF treatment is filgrastim (Neupogen®). In some embodiments, immunotherapy which may be used in combination with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, of according to any of the methods described above is an immune checkpoint inhibitor. In some embodiments, immunotherapy includes one or more immune checkpoint inhibitors. In some embodiments, the immune checkpoint inhibitor is a CTLA4 inhibitor, a PD-1 inhibitor, or a PD-L1 inhibitor. In some embodiments, the CTLA-4 inhibitor is ipilimumab (Yervoy®) or tremelimumab (CP-675,206). In some embodiments, the PD-1 inhibitor is pembrolizumab (Keytruda®) or nivolumab (Opdivo®). In some embodiments, the PD-L1 inhibitor is atezolizumab (Tecentriq®), avelumab (Bavencio®), or durvalumab (Imfinzi™). In some embodiments, the PD-1 inhibitor is RN888 (sasanlimab). In some embodiments, immunotherapy which may be used in combination with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, of according to any of the methods described above is an mRNA-based immunotherapy. In some embodiments, the mRNA-based immunotherapy is CV9104 (see, for example, Rausch et al. (2014) Human Vaccine Immunother 10(11): 3146-52; and Kubler et al. (2015) J. Immunother Cancer 3:26). In some embodiments, immunotherapy which may be used in combination with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, of according to any of the methods described above is a treatment with oncolytic viruses. In some embodiments, the oncolytic virus treatment is talimogene laherparepvec (T-VEC; Imlygic®). In some embodiments, immunotherapy which may be used in combination with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, of According to any of the methods described above is a cancer vaccine. In some embodiments, the cancer vaccine is a human papillomavirus (HPV) vaccine. In some embodiments, the HPV vaccine is Gardasil®, Gardasil9® or Cervarix®. In some embodiments, the cancer vaccine is a hepatitis B virus (HBV) vaccine. In some embodiments, the HBV vaccine is Engerix-B®, Recombivax HB®, or GI-13020 (Tarmogen®). In some embodiments, the cancer vaccine is Twinrix® or Pediarix®. In some embodiments, the cancer vaccine is BiovaxID®, Oncophage®, GVAX, ADXS11-001, ALVAC-CEA, PROSTVAC®, Rindopepimut®, CimaVax-EGF, lapuleucel-T (APC8024; Neuvenge™), GRNVAC1, GRNVAC2, GRN-1201, hepcortespenlisimut-L (Hepko-V5), DCVAX®, SCIB1, BMT CTN 1401, PrCa VBIR, PANVAC, ProstAtak®, DPX-Survivac or viagenpumatucel-L (HS-110). In some embodiments, immunotherapy which may be used in combination with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, of according to any of the methods described above is a peptide vaccine. In some embodiments, the peptide vaccine is nelipepimut-S (E75) (NeuVax™), IMA901 or SurVaxM (SVN53-67). In some embodiments, the cancer vaccine is a personal neoantigen immunogenic vaccine (see, for example, Ott et al. (2017) Nature 547: 217-221; Sahin et al. (2017) Nature 547: 222 -226). In some embodiments, the cancer vaccine is RGSH4K or NEO-PV-01. In some embodiments, the cancer vaccine is a DNA-based vaccine. In some embodiments, the DNA-based vaccine is a mammaglobin-A DNA vaccine (see, for example, Kim etal. (2016) Oncolmmunology 5(2): el069940). In some embodiments, immunotherapy which may be used in combination with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, of according to any of the methods described above is a cellular immunotherapy (for example, treatment with adoptive T lymphocytes, treatment with dendritic cells, treatment with natural killer cells). In some embodiments, the cellular immunotherapy is sipuleucel-T (APC8015; Provenge™; Plosker (2011) Drugs 71(1): 101-108). In some embodiments, cellular immunotherapy includes cells that express a chimeric antigen receptor (CAR). In some embodiments, cellular immunotherapy is a CAR T cell treatment. In some embodiments, the CAR T cell therapy is tisagenlecleucel (Kymriah™). In some embodiments, the antineoplastic agent that can be used in combination with a compound of Formula I, I-A, II, III, IV or V, or a pharmaceutically acceptable salt thereof, according to any of the methods described above is a cytotoxic chemotherapeutic agent. Non-limiting examples of cytotoxic chemotherapeutic agents include arsenic trioxide, bleomycin, cabazitaxel, capecitabine, carboplatin, cisplatin, cyclophosphamide, cytarabine, dacarbazine, daunorubicin, docetaxel, doxorubicin, etoposide, 5fluorouracil, folinic acid, gemcitabine, irinotecan, lomustine, methotrexate, mitomycin C, oxaliplatin, paclitaxel, pemetrexed, temozolomide and vincristine, and combinations of these, for example, Nordic FLOX (fluorouracil, folinic acid and oxaliplatin), FOLFOXIRI (oxaliplatin, irinotecan and fluorouracil), FOLFIRI (folinic acid, fluorouracil and irinotecan) or CAPEOX (capecitabine and oxaliplatin). In some embodiments, the antineoplastic agent which may be used in combination with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, according to any of the methods described above is a treatment directed at angiogenesis. Non-limiting examples of treatments targeting angiogenesis include aflibercept and bevacizumab. In some embodiments, the antineoplastic agent which may be used in combination with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, according to any of the methods described above includes modulators of the apoptotic pathway (for example, obataclax). In some embodiments, the antineoplastic treatment which may be used in combination with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, according to any of the methods described above is radiotherapy. Non-limiting examples of radiation therapy include external beam radiation treatment (e.g., external beam treatment using kilovoltage X-rays or megavoltage X-rays) or internal radiation therapy. Internal radiation therapy (also called brachytherapy) may include the use of, for example, low-dose internal radiation therapy or high-dose internal radiation therapy. Low-dose internal radiation therapy includes, for example, inserting small radioactive pellets (also called seeds) into cancerous tissue in or near the subject. High-dose internal radiation therapy includes, for example, inserting a thin tube (e.g., catheter) or implant into or near cancerous tissue in the subject and delivering a high dose of radiation to the thin tube or implant with a radiation machine. Methods for performing radiotherapy on a subject having cancer are known in the art. In embodiments where the tumor is a CNS tumor, radiation therapy may include whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS), such as Cyberknife®, XKnife®, Gamma knife® or ExacTrac®. In some embodiments, the antineoplastic treatment which may be used in combination with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, according to any of the methods described above is surgery. Non-limiting examples of surgery include, for example, open surgery or minimally invasive surgery. Surgery may include, for example, at least a partial resection of the tumor, removing an entire tumor, reducing the size of a tumor, or removing a tumor that is causing pain or pressure in the subject. Methods for performing open surgery and minimally invasive surgery on a subject having cancer are known in the art. In some embodiments, the additional treatment includes any of the antineoplastic treatments or agents listed above that are standard of care treatments for cancer, wherein the cancer has a BRAF mutation. In one embodiment, provided herein is a method of treating a subject having a BRAF-associated tumor (e.g., any of the BRAF-associated tumors described herein) comprising administering a therapeutically effective amount of a compound. of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, for a period of time, wherein the subject is administered a MEK inhibitor (e.g., any of the MEK inhibitors disclosed herein) during said period of time. In one embodiment, the MEK inhibitor is binimetinib, or a pharmaceutically acceptable salt thereof. In one embodiment, the compound of Formula I is a compound selected from Examples 1164 or a pharmaceutically acceptable salt thereof. In one embodiment, provided herein is a method of treating a subject having a BRAF-associated tumor (e.g., any of the BRAF-associated tumors described herein) comprising administering a therapeutically effective amount of a compound. of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, for a period of time, wherein the subject is administered a BRAF inhibitor (e.g., any of the BRAF inhibitors disclosed herein, including a second compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt of this) during said period of time. In one embodiment, the compound is an iviA / a / zuzz / u i o / u j compound selected from Examples 1-164 or a pharmaceutically acceptable salt thereof. In one embodiment, provided herein is a method of treating a subject having a BRAF-associated tumor (e.g., any of the BRAF-associated tumors described herein) comprising administering a therapeutically effective amount of a compound. of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, for a period of time, wherein the subject is administered an EGFR inhibitor (e.g., any of the EGFR inhibitors disclosed herein) during such period of time. In one embodiment, the compound is a compound selected from Examples 1-164 or a pharmaceutically acceptable salt thereof. In one embodiment, the tumor is lung cancer. In one embodiment, provided herein is a method of treating a subject having a BRAF-associated tumor (e.g., any of the BRAF-associated tumors described herein) comprising administering a therapeutically effective amount of a compound. of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, for a period of time, wherein the subject is administered a HER2 inhibitor and / or HER3 during said period of time. In one embodiment, the compound is a compound selected from Examples 1-164 or a pharmaceutically acceptable salt thereof. In one embodiment, provided herein is a method of treating a subject having a BRAF-associated tumor (e.g., any of the BRAF-associated tumors described herein) comprising administering a therapeutically effective amount of a compound. of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, for a period of time, wherein the subject is administered an Axl inhibitor (for example, any of the Axl inhibitors disclosed herein) during said period of time. In one embodiment, the compound is a compound selected from Examples 1-164 or a pharmaceutically acceptable salt thereof. In one embodiment, provided herein is a method of treating a subject having a BRAF-associated tumor (e.g., any of the BRAF-associated tumors described herein) comprising administering a therapeutically effective amount of a compound. of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, for a period of time, wherein the subject is administered a SCSI inhibitor (e.g., any of the SOS1 inhibitors disclosed herein) during said period of time. In one embodiment, compound I is a compound selected from Examples 1-164 or a commercially acceptable salt. IVIA / a / ZUZZ / U I 3 / UJ pharmaceutical view of this. In one embodiment, provided herein is a method of treating a subject having a BRAF-associated tumor (e.g., any of the BRAF-associated tumors described herein), comprising administering a therapeutically effective amount of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, for a period of time, wherein the subject is administered an inhibitor of signal transduction (for example, any of the signal transduction inhibitors disclosed herein) during said period of time. In one embodiment, the compound is a compound selected from Examples 1-164 or a pharmaceutically acceptable salt thereof. In one embodiment, provided herein is a method of treating a subject having a BRAF-associated tumor (e.g., any of the BRAF-associated tumors described herein) comprising administering a therapeutically effective amount of a compound. of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, for a period of time, wherein the subject is administered a point inhibitor control (for example, any of the checkpoint inhibitors disclosed herein) during said period of time. In one embodiment, the compound is a compound selected from Examples 1-164 or a pharmaceutically acceptable salt thereof. In one embodiment, provided herein is a method of treating a subject having a BRAF-associated tumor (e.g., any of the BRAF-associated tumors described herein) comprising administering a therapeutically effective amount of a compound. of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, for a period of time, wherein the subject is administered a modulator of the apoptotic pathway (e.g., any of the apoptotic pathway modulators disclosed herein) during said period of time. In one embodiment, the compound is a compound selected from Examples 1-164 or a pharmaceutically acceptable salt thereof. In one embodiment, provided herein is a method of treating a subject having a BRAF-associated tumor (e.g., any of the BRAF-associated tumors described herein) comprising administering a therapeutically effective amount of a compound. of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, for a period of time, wherein the subject is administered a cytotoxic chemotherapeutic agent (e.g., any of the cytotoxic chemotherapeutic agents disclosed herein) during said period of time. In one embodiment, the compound is a compound selected from Examples 1-164 or a pharmaceutically acceptable salt thereof. In one embodiment, provided herein is a method of treating a subject having a BRAF-associated tumor (e.g., any of the BRAF-associated tumors described herein) comprising administering a therapeutically effective amount of a compound. of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, over a period of time, wherein the subject is administered a treatment directed at angiogenesis (e.g., any of the angiogenesis-targeting treatments disclosed herein) during said period of time. In one embodiment, the compound of Formula I is a compound selected from Examples 1-164 or a pharmaceutically acceptable salt thereof. In one embodiment, provided herein is a method of treating a subject having a BRAF-associated tumor (e.g., any of the BRAF-associated tumors described herein) comprising administering a therapeutically effective amount of a compound. of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, for a period of time, wherein the subject is administered an agent directed to the immune system (for example, any of the agents targeting the immune system disclosed herein) during said period of time. In one embodiment, the compound of Formula I is a compound selected from Examples 1-164 or a pharmaceutically acceptable salt thereof. Also provided herein is a pharmaceutical combination for treating a BRAF-associated tumor in a subject in need thereof, comprising (a) a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, and (b) at least one additional antineoplastic agent (e.g., any of the exemplary additional antineoplastic agents described herein or known in the art), wherein the compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, and the at least one additional antineoplastic agent are separately formulated for simultaneous use , separate or sequential for the treatment of the tumor, wherein the amounts of the compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, and of the additional antineoplastic agent are jointly effective in treating the tumor; (i) the use of such combination for the preparation of a medicament for the treatment of tumor; and (ii) a commercial package or product comprising such combination as a combination preparation for use simultaneously, separately or sequentially; and a method of treating a tumor in a subject in need. The term pharmaceutical combination, as used herein, refers to a non-fixed combination of the active ingredients. The term "non-fixed combination" means that a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, and at least one additional antineoplastic agent are formulated as separate compositions or doses, whereby they can be administered to a subject in need simultaneously, concurrently or sequentially with variable time intervals, wherein such administration provides effective levels of the two or more compounds in the subject's body. These also apply to cocktail therapies, for example the administration of three or more active ingredients Accordingly, also provided herein is a method of treating a BRAF-associated tumor, comprising administering to a subject in need thereof a pharmaceutical combination for treating said tumor comprising (a) a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, and (b) an additional antineoplastic agent for use simultaneously, separately or sequentially for the treatment of the tumor, wherein the amounts of the compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, and the additional antineoplastic agent are together effective in treating the tumor . In one embodiment, the BRAF-associated tumor is a malignant tumor, and the additional antineoplastic agent is an antineoplastic agent, for example, any of the antineoplastic agents described herein. In some embodiments, the compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, and the additional antineoplastic agent are administered as simultaneously as separate doses. In some embodiments, the compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, and the additional antineoplastic agent are administered as doses separated sequentially in any order, for example, at a rate of daily or intermittent doses, in therapeutically effective amounts as a whole. Additional antineoplastic agents may be administered with one or more doses of the compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of this, as part of the same or separate dosage forms, through the same or different routes of administration, and / or with the same or different administration schedules in accordance with standard pharmaceutical practice known to the public. of the mid-level trade. In some embodiments, the BRAF-associated tumor is a malignant BRAF-associated tumor (i.e., a BRAF-associated cancer). In some embodiments, the BRAF-associated cancer is a BRAF-associated CNS cancer. In some embodiments, the BRAF-associated CNS cancer is a BRAF-associated metastatic cancer. In some embodiments, the BRAF-associated metastatic cancer is metastatic melanoma. In some embodiments, the BRAF-associated metastatic cancer is metastatic colorectal cancer. In some embodiments, the BRAF-associated metastatic cancer is metastatic non-small cell lung cancer. In some embodiments, the BRAF-associated metastatic cancer is metastatic thyroid cancer. In some embodiments, the BRAF-associated metastatic cancer is metastatic ovarian cancer. In some embodiments, the BRAF-associated metastatic cancer is intracranial LMD or extracranial LMD. In some embodiments, BRAF-associated CNS cancer is a primary brain tumor. In some embodiments, the BRAF-associated tumor is a benign CNS tumor. In some embodiments, the cancer is selected from lung cancer (e.g., non-small cell lung cancer and small cell lung cancer), melanoma, colorectal cancer, breast cancer, pancreatic cancer, thyroid cancer. , prostate cancer, adenoid cystic carcinoma, appendiceal cancer, small intestine cancer, head and neck squamous cell carcinoma, angiosarcoma and CNS tumors. In some embodiments of any of the methods described herein, a subject has a BRAF-associated tumor (e.g., a benign, malignant or metastatic tumor), where the subject has been treated with a prior treatment or a treatment standard (for example, treatment with one or more antineoplastic agents other than a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof and / or radiotherapy and / or surgery), wherein said BRAF-associated tumor has become resistant or intolerant to said prior treatment. In some embodiments, a subject has a BRAF-associated tumor (e.g., a locally advanced or metastatic tumor) that does not have standard treatment. In one embodiment, the method comprises administering a compound of Formula I selected from Examples 1-164, or a pharmaceutically acceptable salt thereof. Accordingly, in one embodiment, a method of treating a subject having a BRAF-associated tumor is provided herein, wherein the subject was previously treated with one or more antineoplastic treatments (e.g., an antineoplastic agent, radiation therapy). and / or surgery), wherein the method comprises administering to the subject a therapeutically effective amount of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a technically acceptable salt pharmacist of this. In one embodiment, the BRAF-associated tumor has become resistant to said prior treatment. In one embodiment, the cancer is a BRAF-associated cancer having a class II mutation. In one embodiment, the class II mutation is a non-V600 mutation. In one embodiment, the non-V600 mutation is G469A, G469R, G469V, Κ601Ε, Κ601Ν, Κ601Τ, L597Q or L597V. In one embodiment, the non-V600 mutation is G469A. In one embodiment, the class II mutation is a BRAF splice variant. In one embodiment, the BRAF splice variant lacks exons 4-8 (also known as p61BRAF(V600E)), exons 4-10, exons 2-8, or exons 2-10. In one embodiment, the BRAF splice variant is p61BRAF(V600E). Non-limiting examples of BRAF-associated cancer types with class II mutations include lung cancer (e.g., non-small cell lung cancer and small cell lung cancer), melanoma, colorectal cancer, breast cancer, pancreatic cancer, thyroid cancer, prostate cancer, adenoid cystic carcinoma, appendiceal cancer, small intestine cancer, head and neck squamous cell carcinoma, angiosarcoma and CNS tumors. In some embodiments, a subject having a BRAF-associated cancer was previously treated with a BRAF inhibitor (i.e., a BRAF inhibitor other than a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof), alone or in combination with another antineoplastic agent, prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In one embodiment, the subject was pretreated with a BRAF inhibitor selected from encorafenib, dabrafenib, vemurafenib, N-[3-(5-chloro-lH-pyrrolo[2,3-b]pyridin-3- ¡lcarbonyl)-2,4-difluorophenyl]propan1-sulfonamide, (3R)-N-(3-[[5-(2-c¡cloprop¡lp¡rimidín-5-yl)-lH-p ¡rrolo[2,3-b]pyridín-3-¡l]carbonyl]-2,4difluorophenyl)-3-fluoropyrrolídin-l-sulfonamide (PLX8394), or a technically acceptable salt pharmacist of these. In one embodiment, the subject was pretreated with a BRAF inhibitor selected from encorafenib, dabrafenib and vemurafenib, or a pharmaceutically acceptable salt thereof. In one embodiment, the BRAF-associated cancer that was treated with the above BRAF inhibitor was a BRAF V600 mutant cancer (e.g., a BRAF V600E or BRAF V600K mutant cancer). In one embodiment, BRAF-associated cancer became resistant to such prior treatment. In one embodiment, the BRAF-associated cancer expressed a BRAF V600 resistance mutation during or after said prior treatment. In one embodiment, the subject developed brain metastasis during said prior treatment. In some embodiments, a subject having a BRAF-associated metastatic melanoma has received treatment with a BRAF inhibitor (i.e., a BRAF inhibitor other than a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof) prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. the pharmaceutical point of view of this. In one embodiment, the subject was pretreated iviA / a / zuzz / u i o i u □ with a BRAF inhibitor selected from encorafenib, dabrafenib, vemurafenib, N-[3-(5-chloro-lHpírrolo[2,3- b]pyridin-3-¡lcarbon¡l)-2,4-difluorophenyl]propan-l-sulfonamide, (3R)-N-(3-[[5-(2c¡cloprop¡lp¡r¡m¡) d¡n-5-¡l)-lH-pyrrolo[2,3-b]p¡r¡din-3-¡l]carbon¡l]-2,4-difluorophen¡l)-3 -fluoropírrolidín-lsulfonamide (PLX8394), or a pharmaceutically acceptable salt thereof. In one embodiment, the subject was pretreated with a BRAF inhibitor selected from encorafenib, dabrafenib and vemurafenib, or a pharmaceutically acceptable salt thereof. In one embodiment, the melanoma became resistant to said prior treatment. In one embodiment, the melanoma expressed a BRAF V600E resistance mutation during or after said pretreatment. In one embodiment, the subject developed brain metastasis during said prior treatment. In some embodiments, a subject having a BRAF-associated metastatic melanoma has received treatment with a BRAF inhibitor (e.g., other than a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof) and a MEK inhibitor prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or an acceptable salt from the pharmaceutical point of view of this. In one embodiment, the subject was pretreated with a BRAF inhibitor selected from encorafenib, dabrafenib, vemurafenib, N-[3(5-chloro-lH-pyrrolo[2,3-b]pyridin-3 -ylcarbon¡l)-2,4-difluorophen¡l]propan-l-sulfonamide and (3R)-N-(3-[[5(2-cyclopropylpyrimidin-5-yl)-lH-pyrrolo[ 2,3-b]pindin-3-yl]carbonyl]-2,4-difluorophenyl)-3-fluoropyrrolidine-lsulfonamide (PLX8394), or a pharmaceutically acceptable salt thereof, and a selected MEK inhibitor of binimetinib, trametinib, cobimetinib, selumetinib, pimasertib, refametinib, mirdametinib, 2-(2-chloro-4-iodophenylamino)-N-(cycloprop¡lmethox¡)-3,4-d¡fluorobenzamide (CI-1040) and 3 -[2(R),3-dihydroxyprop¡l]-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8-methylpyrid[2,3d]pyrim¡ din-4,7(3H,8H)-dione (TAK-733), or a pharmaceutically acceptable salt thereof. In one embodiment, the subject was pretreated with a BRAF inhibitor selected from encorafenib, dabrafenib and vemurafenib, or a pharmaceutically acceptable salt thereof, and a MEK inhibitor selected from binimetinib, trametinib and cobimetinib, or a pharmaceutically acceptable salt thereof. In one embodiment, the subject was pretreated with encorafenib, or a pharmaceutically acceptable salt thereof, and binimetinib, or a pharmaceutically acceptable salt thereof. In one embodiment, the subject was pretreated with dabrafenib, or a pharmaceutically acceptable salt thereof, and trametinib, or a pharmaceutically acceptable salt thereof. In one embodiment, the subject was pretreated with vemurafenib, or a pharmaceutically acceptable salt thereof, and cobimetinib, or a pharmaceutically acceptable salt thereof. In one embodiment, the melanoma became resistant to said prior treatment. In one embodiment, the melanoma expressed a BRAF V600E resistance mutation during or after said pretreatment. In one embodiment, the subject developed brain metastasis during said prior treatment. In some embodiments, a subject having a BRAF-associated metastatic melanoma has received treatment with one or more checkpoint inhibitors (e.g., any of the checkpoint inhibitors disclosed herein, e.g., an inhibitor of CTLA4, a PD-1 inhibitor and / or a PD-L1 inhibitor) before treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a salt acceptable from the pharmaceutical point of view of this. In one embodiment, the subject was pretreated with one or more checkpoint inhibitors independently selected from ipilimumab, nivolumab, pembrolizumab, and avelumab. In one embodiment, the melanoma became resistant to said prior treatment. In one embodiment, the subject developed brain metastasis during said prior treatment. In some embodiments, a subject having a BRAF-associated metastatic melanoma has received treatment with one or more PI3K inhibitors prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In one embodiment, the subject was pretreated with one or more PI3K inhibitors selected from buparlisib (BKM120), alpelisib (BYL719), samotolisib (LY3023414), 8-[(lR)-l-[(3.5- difluorophenyl)amino]ethyl]-N,N-dimethyl-2-(morpholin4-¡l)-4-oxo-4H-chromen-6-carboxamide (AZD8186), tenalisib (RP6530), sodium hydrochloride voxtalisib (SAR245409), gedatolisib (PF-05212384), panulisib (P-7170), taselisib (GDC-0032), trans-2-amino-8-[4-(2h¡drox¡ethox¡)cyclohex¡l ]-6-(6-methoxy¡p¡r¡d¡n-3-¡l)-4-met¡lp¡r¡do[2,3-d]p¡r¡m¡d¡n-7 (8H)-one (PF04691502), duvelisib (ABBV-954), N2-[4-oxo-4-[4-(4-oxo-8-phenyl-4H-l-benzopyran-2¡l acetate )morpholin-4-ium-4-ylmethox¡]butyríl]-L-arginyl-gl¡c¡l-L-aspartyl-L-serine (SF-1126), pictilisib (GDC-0941), 2-met¡ acid l-l-[2-methyl¡l-3-(trifluoromethyl)benzyl]-6-(morpholín-4-¡l)-lH-benzim¡dazole-4-carboxylic acid (GSK2636771) , idelalisib (GS-1101), thresholdisib tosylate (TGR-1202), pictilisib (GDC-0941), copanlisib hydrochloride (BAY 84-1236), dactolisib (BEZ-235), l-(4-[5-[ 5-amino-6-(5-tert-butyl-l,3,4oxad¡azol-2-¡l)pysraz¡n-2-¡l]-l-ethyl¡l-lH-l,2,4- triazol-3-¡l]p¡perídin-l-¡l)-3-hydroxy¡propan-l-one (AZD8835), 5-[6,6-dimet¡l-4 -(morphol¡n-4-¡l)-8,9-d¡hydro-6H-[l,4]oxaz¡no[4,3-e]pur¡n-2-¡l]p¡r¡ m¡d¡n-2-am¡na (GDC-0084) everolimus, rapamycin, perifosine, sirolimus and temsirolimus. In one embodiment, the subject was pretreated with buparlisib or alpelisib, alone or in combination. In one embodiment, the melanoma became resistant to said prior treatment. In one embodiment, the subject developed brain metastasis during said prior treatment. In one embodiment, the subject developed brain metastasis during said prior treatment. In some embodiments, a subject having a metastatic melanoma associated with BRAF has received treatment with a BRAF inhibitor other than a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, and one or more checkpoint inhibitors (e.g., any of the checkpoint inhibitors disclosed herein, e.g., a CTLA-4 inhibitor, a PD-1 inhibitor and / or a PD-L1 inhibitor) before of treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In one embodiment, the subject was pretreated with a BRAF inhibitor selected from encorafenib, dabrafenib, vemurafenib, N-[3-(5-chloro-lH-pyrrolo[2,3b]pyridin-3-ylcarbon¡l) -2,4-difluorophenyl]propan-l-sulfonamide and (3R)-N-(3-[[5-(2-cyclopropylp¡r¡m¡d¡n-5¡l)-lH-pyrrolo[2, 3-b]pyridn-3-¡l]carbon¡l]-2,4-difluorophenyl)-3-fluorop¡rrolidin-l-sulfonamide (PLX8394), or an acceptable salt from the pharmaceutical point of view of these, and one or more independently selected checkpoint inhibitors of ipilimumab, nivolumab and pembrolizumab. In one embodiment, the melanoma became resistant to said prior treatment. In one embodiment, the subject developed brain metastasis during said prior treatment. In some embodiments, a subject having a BRAF-associated metastatic melanoma has received treatment with a BRAF inhibitor (e.g., other than a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof), a MEK inhibitor, and one or more checkpoint inhibitors (e.g., any of the checkpoint inhibitors disclosed herein, e.g. , a CTLA-4 inhibitor, a PD-1 inhibitor and / or a PD-L1 inhibitor) prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In one embodiment, the subject was pretreated with a BRAF inhibitor selected from encorafenib, dabrafenib, vemurafenib, N-[3-(5-chloro-lH-pyrrolo[2,3-b]pyridín- 3-¡lcarbon¡l)-2,4-difluorophenyl]propan-l-sulfonamide (PLX4720) and (3R)-N-(3-[[5-(2-cyclopropylpyrimidin-5-yl )-1H-pyrrolo[2,3-b]pyridin-3-yl]carbonyl]-2,4-difluorophenyl)-3fluoropyrrolidin-l-sulfonamide (PLX8394), or a technically acceptable salt pharmaceutical of these, a MEK inhibitor selected from binimetinib, trametinib, cobimetinib, selumetinib, pimasertib, refametinib, mirdametinib, 2-(2-chloro-4-iodophenylam¡no)-N-(c¡cloprop¡lmethox¡)-3 ,4difluorobenzamide (CI-1040) and 3-[2(R),3-dihydroxypropyl]-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8methylpyrido[2,3 -d]pyrimidin-4,7(3H,8H)-dione (TAK-733), or a pharmaceutically acceptable salt thereof, and one or more checkpoint inhibitors (e.g., any of checkpoint inhibitors disclosed herein, for example, a CTLA-4 inhibitor, a PD-1 inhibitor and / or a PD-L1 inhibitor). In one embodiment, the subject was pretreated with a BRAF inhibitor selected from encorafenib, dabrafenib and vemurafenib, or a pharmaceutically acceptable salt thereof, a MEK inhibitor selected from binimetinib, trametinib and cobimetinib, and one or more checkpoint inhibitors independently selected from ipilimumab, nivolumab, pembrolizumab and avelumab. In one embodiment, the melanoma became resistant to said prior treatment. In one embodiment, the subject developed brain metastasis during said prior treatment. In some embodiments, a subject having a BRAF-associated metastatic melanoma has received treatment with one or more alkylating agents prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V. , or a pharmaceutically acceptable salt thereof. In one embodiment, the subject was pretreated with one or more alkylating agents selected from temozolomide, fotemustine, lomustine and carmustine. In one embodiment, the subject was pretreated with temozolomide. In one embodiment, the melanoma became resistant to said prior treatment. In one embodiment, the subject developed brain metastasis during said prior treatment. In some embodiments, a subject having a BRAF-associated metastatic colorectal cancer has received treatment with a BRAF inhibitor other than a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, a MEK inhibitor and an EGFR inhibitor prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt of this. In one embodiment, the subject was pretreated with a BRAF inhibitor selected from encorafenib, dabrafenib, vemurafenib, N-[3-(5-chloro-lH-pyrrolo[2,3-b]pyri). d¡n-3-ylcarbon¡l)-2,4-difluorophen¡l]propan1-sulfonamide (PLX4720) and (3R)-N-(3-[[5-(2-c¡c¡clopropylpyrimidin-5- l)-lH-pyrrolo[2,3-b]pyridn-3¡l]carbon¡l]-2,4-difluorophenyl)-3-fluorop¡rrol¡din-l-sulfonam¡ da (PLX8394), or a pharmaceutically acceptable salt thereof, a MEK inhibitor selected from binimetinib, trametinib, cobimetinib, selumetinib, pimasertib, refametinib, mirdametinib, 2-(2-chloro-4-iodophenylamino)- N(cyclopropylmethoxy¡)-3,4-difluorobenzamide (CI-1040) and 3-[2(R),3-dihydroxy¡propyl]-6-fluoro-5-(2-fluoro4-iodophenylamino )-8-methyllipid[2,3-d]pyrimidin-4,7(3H,8H)-dione (TAK-733), or a commercially acceptable salt pharmaceutical view of these, and an EGFR inhibitor selected from cetuximab, panitumumab, osimertinib, erlotinib, gefitinib, necitumumab, neratinib, lapatinib, vandetanib and brigatinib. In one embodiment, the subject was pretreated with a BRAF inhibitor selected from encorafenib, dabrafenib and vemurafenib, or a pharmaceutically acceptable salt thereof, a MEK inhibitor selected from binimetinib, trametinib and cobimetinib, or a pharmaceutically acceptable salt thereof, and an EGFR inhibitor selected from cetuximab and panitumumab. In one embodiment, the subject was pretreated with encorafenib, or a pharmaceutically acceptable salt thereof, binimetinib, or a pharmaceutically acceptable salt thereof, and cetuximab. In one embodiment, the subject was pretreated with dabrafenib, or a pharmaceutically acceptable salt thereof, trametinib, or a pharmaceutically acceptable salt thereof, and panitumumab. In one embodiment, the colorectal cancer became resistant to said prior treatment. In one embodiment, the subject developed brain metastasis during said prior treatment. In some embodiments, a subject having BRAF-associated metastatic colorectal cancer has received treatment with an EGFR inhibitor prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V. , or a pharmaceutically acceptable salt thereof. In some embodiments, a subject having a BRAF-associated metastatic colorectal cancer (e.g., a BRAF-mutant metastatic colorectal cancer) has received treatment with an EGFR inhibitor selected from cetuximab, panitumumab, osimertinib, erlotinib, gefitinib, necitumumab, neratinib, lapatinib, vandetanib and brigatinib and a BRAF inhibitor selected from encorafenib, dabrafenib, vemurafenib, N-[3-(5-chloro-lH-pyrrolo[2,3-b]pyridin-3- ¡lcarbon¡l)-2,4-difluorophen¡l]propan-l-sulfonamide (PLX4720) and (3R)-N-(3-[[5-(2-c¡cloprop¡lp¡rim) ¡d¡n-5-¡l)-lH-pyrrolo[2,3-b]pyr¡d¡n-3-yl]carbonyl]-2,4-difluorophen¡l)-3fluoropyrrolidine -l-sulfonamide (PLX8394), or a pharmaceutically acceptable salt thereof. In some embodiments, a subject having BRAF-associated metastatic colorectal cancer has received treatment with cetuximab or panitumumab prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In one embodiment, the colorectal cancer became resistant to said prior treatment. In one embodiment, the subject developed brain metastasis during said prior treatment. In some embodiments, a subject having BRAF-associated metastatic colorectal cancer has received treatment with an EGFR inhibitor and one or more cytotoxic chemotherapeutic agents prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In some embodiments, a subject having BRAF-associated metastatic colorectal cancer has received treatment with an EGFR inhibitor selected from cetuximab, panitumumab, osimertinib, erlotinib, gefitinib, necitumumab, neratinib, lapatinib, vandetanib and brigatinib, and one or plus cytotoxic chemotherapeutic agents. In some embodiments, a subject having a BRAF-associated metastatic colorectal cancer (e.g., a BRAF-mutant metastatic colorectal cancer) has received treatment with an EGFR inhibitor selected from cetuximab or panitumumab and one or more cytotoxic chemotherapeutic agents. , such as Nordic FLOX (fluorouracil, folinic acid and oxaliplatin) before treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt of this. In one embodiment, colorectal cancer is iviA / a / zuzz / u i 3 / uj 100 became resistant to said previous treatment. In one embodiment, the subject developed brain metastasis during said prior treatment. In some embodiments, a subject having BRAF-associated metastatic colorectal cancer has received treatment with an EGFR inhibitor and a BRAF inhibitor prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In some embodiments, a subject having BRAF-associated metastatic colorectal cancer has received treatment with an EGFR inhibitor selected from cetuximab, panitumumab, osimertinib, erlotinib, gefitinib, necitumumab, neratinib, lapatinib, vandetanib and brigatinib and an inhibitor of BRAF selected from encorafenib, dabrafenib, vemurafenib, N-[3-(5-chloro-lH-pyrrolo[2,3-b]pyridín-3ylcarbon¡l)-2,4-difluorophenyl]propan- l-sulfonamide (PLX4720) and (3R)-N-(3-[[5-(2-cyclopropylpyrimidin-5yl)-lH-pyrrolo[2,3-b]pindin-3-yl]carbonyl]-2 ,4-difluorophenyl)-3-fluoropyrrolidin-l-sulfonamide (PLX8394), or a pharmaceutically acceptable salt thereof. In one embodiment, the subject was pretreated with an EGFR inhibitor selected from cetuximab and panitumumab and a BRAF inhibitor selected from encorafenib, dabrafenib and vemurafenib, or a pharmaceutically acceptable salt thereof. In one embodiment, the subject was pretreated with encorafenib, or a pharmaceutically acceptable salt thereof, and cetuximab. In one embodiment, the subject was pretreated with vemurafenib, or a pharmaceutically acceptable salt thereof, and panitumumab. In one embodiment, the subject was pretreated with dabrafenib, or a pharmaceutically acceptable salt thereof, and panitumumab. In one embodiment, the colorectal cancer became resistant to said prior treatment. In one embodiment, the subject developed brain metastasis during said prior treatment. In some embodiments, a subject having metastatic colorectal cancer has received treatment with a MEK inhibitor and one or more checkpoint inhibitors (e.g., any of the checkpoint inhibitors disclosed herein, e.g. a CTLA-4 inhibitor, a PD-1 inhibitor and / or a PD-L1 inhibitor) prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt of this. In one embodiment, the subject was pretreated with a MEK inhibitor selected from binimetinib, trametinib, cobimetinib, selumetinib, pimasertib, refametinib, mirdametinib, 2-(2-chloro-4-iodophenylamino)-N(cyclopropylmethox¡)- 3,4-difluorobenzamide (CI-1040) and 3-[2(R),3-dihydroxypropyl]-6-fluoro-5-(2-fluoro4-iodophenylamino)-8- methyllipid[2,3-d]pyrimidin-4,7(3H,8H)-dione (TAK-733), and one or more checkpoint inhibitors (for example, any of the checkpoint inhibitors checkpoint disclosed herein, for example, a CTLA-4 inhibitor, a PD-1 inhibitor and / or a PD-L1 inhibitor). In In one embodiment, the subject was pretreated with a MEK inhibitor selected from binimetinib, trametinib and cobimetinib, and one or more checkpoint inhibitors independently selected from ipilimumab, nivolumab, pembrolizumab and avelumab. In one embodiment, the subject was pretreated with the MEK inhibitor binimetinib and the checkpoint inhibitors nivolumab and ipilimumab. In one embodiment, the subject was pretreated with the MEK inhibitor binimetinib and the checkpoint inhibitor pembrolizumab. In one embodiment, the subject was pretreated with the MEK inhibitor binimetinib and the checkpoint inhibitor avelumab. In one embodiment, the subject was pretreated with the MEK inhibitor trametinib and the checkpoint inhibitors nivolumab and ipilimumab. In one embodiment, the colorectal cancer became resistant to said prior treatment. In one embodiment, the subject developed brain metastasis during said prior treatment. In some embodiments, a subject having BRAF-associated metastatic colorectal cancer has received treatment with one or more checkpoint inhibitors (e.g., any of the checkpoint inhibitors disclosed herein, e.g., a CTLA-4 inhibitor, a PD-1 inhibitor and / or a PD-L1 inhibitor) prior to treatment with Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a salt acceptable from the pharmaceutical point of view of this. In one embodiment, the subject was pretreated with one or more checkpoint inhibitors independently selected from ipilimumab, nivolumab, pembrolizumab, and avelumab. In one embodiment, the subject was pretreated with nivolumab. In one embodiment, the colorectal cancer became resistant to said prior treatment. In one embodiment, the subject developed brain metastasis during said prior treatment. In some embodiments, a subject having BRAF-associated metastatic colorectal cancer has received treatment with one or more cytotoxic chemotherapeutic agents prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In some embodiments, a subject who has a BRAF-associated metastatic colorectal cancer (e.g., a BRAF mutant metastatic colorectal cancer) has received treatment with oxaliplatin, irinotecan, FOLFOXIRI (oxaliplatin, irinotecan and fluorouracil), FOLFIRI (acid folinic, fluorouracil and irinotecan) or CAPEOX (capecitabine and oxaliplatin) before treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt of this. In one embodiment, the colorectal cancer became resistant to said prior treatment. In one embodiment, the subject developed brain metastasis during said prior treatment. In some embodiments, a subject having metastatic colorectal cancer 102 associated with BRAF has received treatment with an antibody treatment and one or more cytotoxic chemotherapeutic agents before treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a salt acceptable from the pharmaceutical point of view of this. In some embodiments, a subject having a BRAF-associated metastatic colorectal cancer (e.g., a BRAF mutant metastatic colorectal cancer) has been treated with an antibody treatment that is bevacizumab and one or more cytotoxic chemotherapeutic agents. In some embodiments, a subject who has BRAF-associated metastatic colorectal cancer (e.g., BRAF-mutant metastatic colorectal cancer) has received treatment with bevacizumab and irinotecan, bevacizumab and FOLFOXIRI (oxaliplatin, irinotecan, and fluorouracil), or bevacizumab and FOLFIRI (folinic acid, fluorouracil and irinotecan) before treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In one embodiment, the colorectal cancer became resistant to said prior treatment. In one embodiment, the subject developed brain metastasis during said prior treatment. In some embodiments, a subject having BRAF-associated metastatic colorectal cancer has received treatment with an EGFR inhibitor, a BRAF inhibitor other than a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, and one or more cytotoxic chemotherapeutic agents prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In some embodiments, a subject having BRAF-associated metastatic colorectal cancer has received treatment with an EGFR inhibitor selected from cetuximab, panitumumab, osimertinib, erlotinib, gefitinib, necitumumab, neratinib, lapatinib, vandetanib and brigatinib, an inhibitor of BRAF selected from encorafenib, dabrafenib, vemurafenib, N-[3-(5-chloro-lH-pyrrolo[2,3-b]pyridín-3-ílcarbonyl)-2,4-difluorophen ¡l]propan-l-sulfonamide (PLX4720) and (3R)-N-(3-[[5-(2-cyclopropylpyrimidin-5-yl)-lH-pyrrolo[2,3-b]pyridin-3 -yl]carbonyl]-2,4-difluorophenyl)-3fluoropyrrolidin-l-sulfonamide (PLX8394), or a pharmaceutically acceptable salt thereof, and one or more cytotoxic chemotherapeutic agents. In some embodiments, a subject having BRAF-associated metastatic colorectal cancer has received treatment with an EGFR inhibitor selected from cetuximab and panitumumab, a BRAF inhibitor that is vemurafenib, or a pharmaceutically acceptable salt of this, and a cytotoxic chemotherapeutic agent which is irinotecan. In one embodiment, the colorectal cancer became resistant to said prior treatment. In one embodiment, the subject developed brain metastasis during said prior treatment. In some embodiments, a subject having a BRAF-associated metastatic colorectal cancer (e.g., a BRAF-mutant metastatic colorectal cancer) has received 103 treatment with an EGFR inhibitor and one or more cytotoxic chemotherapeutic agents before treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt of this. In some embodiments, a subject having a BRAF-associated metastatic colorectal cancer (e.g., a BRAF-mutant metastatic colorectal cancer) has received treatment with an EGFR inhibitor selected from cetuximab, panitumumab, osimertinib, erlotinib, gefitinib, necitumumab, neratinib, lapatinib, vandetanib and brigatinib, and one or more cytotoxic chemotherapeutic agents. In some embodiments, a subject having a BRAF-associated metastatic colorectal cancer (e.g., a BRAF-mutant metastatic colorectal cancer) has received treatment with an EGFR inhibitor selected from cetuximab and panitumumab, and a cytotoxic chemotherapeutic agent that It is irinotecan or FOLFIRI (folinic acid, fluorouracil and irinotecan). In one embodiment, the colorectal cancer became resistant to said prior treatment. In one embodiment, the subject developed brain metastasis during said prior treatment. In some embodiments, a subject having BRAF-associated metastatic colorectal cancer has received treatment with surgery prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt of this. In one embodiment, the subject became resistant to said prior treatment. In one embodiment, the subject developed brain metastasis during said prior treatment. In some embodiments, a subject having BRAF-associated metastatic colorectal cancer has received treatment with surgery followed by treatment with a BRAF inhibitor other than a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, a MEK inhibitor and an EGFR inhibitor prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In one embodiment, the subject was pretreated with surgery and pretreated with a BRAF inhibitor selected from encorafenib, dabrafenib, vemurafenib, N-[3-(5-chloro-lH-pyrrolo[2,3-b] pyrid¡n3-¡lcarbonyl)-2,4-difluorophen¡l]propan-l-sulfonamide (PLX4720) and (3R)-N-(3-[[5-(2-cyclopropylpyrimid¡n5) -¡l)-lH-pyrrolo[2,3-b]pindin-3-¡l]carbon¡l]-2,4-difluorophen¡l)-3-fluoropyrrolo¡din-l-sulfonam¡ da (PLX8394), or a pharmaceutically acceptable salt thereof, a MEK inhibitor selected from binimetinib, trametinib, cobimetinib, selumetinib, pimasertib, refametinib, mirdametinib, 2-(2-chloro-4-iodophenylamino)- N-(cyclopropylmethoxy)-3,4-difluorobenzamide (CI-1040) and 3-[2(R),3-dihydroxypropyl]-6-fluoro-5-(2-fluoro-4-iodophene) lamino)-8-methylpyrido[2,3-d]pyrimidin4,7(3H,8H)-dione (TAK-733), or a pharmaceutically acceptable salt thereof, and an EGFR inhibitor selected from cetuximab , panitumumab, osimertinib, erlotinib, gefitinib, iviA / a / zuzz / u i o / u j 104 necitumumab, neratinib, lapatinib, vandetanib and brigatinib. In one embodiment, the subject is pretreated with surgery and pretreated with a BRAF inhibitor selected from encorafenib, dabrafenib and vemurafenib, a MEK inhibitor selected from binimetinib, trametinib and cobimetinib, or a medically acceptable salt. pharmaceutical view of these, and an EGFR inhibitor selected from cetuximab and panitumumab. In one embodiment, the colorectal cancer became resistant to said prior treatment. In one embodiment, the subject developed brain metastasis during said prior treatment. In some embodiments, a subject having BRAF-associated metastatic colorectal cancer has received treatment with radiotherapy (e.g., whole brain radiotherapy or stereotactic radiosurgery) prior to treatment with a compound of Formula I, Formula I-A, Formula II , Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In one embodiment, the subject became resistant to said prior treatment. In one embodiment, the subject developed brain metastasis during said prior treatment. In some embodiments, a subject having BRAF-associated metastatic colorectal cancer has received treatment with radiation therapy (e.g., whole brain radiation therapy or stereotactic radiosurgery) followed by treatment with a BRAF inhibitor, a MEK inhibitor, and a BRAF inhibitor. of EGFR before treatment with a compound of Formula I, Formula ΙΑ, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In one embodiment, the subject was pretreated with radiotherapy and pretreated with a BRAF inhibitor selected from encorafenib, dabrafenib, vemurafenib, N-[3-(5-chloro-lH-pyrrolo[2,3- b]pyridin-3-ylcarbonyl)-2,4-difluorophen¡l]propan-l-sulfonamide (PLX4720) and (3R)-N-(3-[[5-(2-cyclopropylpyrimidin-5- il)-lH-pyrrolo[2,3-b]pyr¡din-3-yl]carbonyl]-2,4-difluorophenyl)-3fluoropyrrolidin-l-sulfonamide (PLX8394), or an acceptable salt from the pharmaceutical point of view of these, a MEK inhibitor selected from binimetinib, trametinib, cobimetinib, selumetinib, pimasertib, refametinib, mirdametinib, 2-(2-chloro-4-iodophenílamino)-N-(c¡cloprop¡ lmethox¡)-3,4difluorobenzamide (CI-1040) and 3-[2(R),3-dihydroxyprop¡l]-6-fluoro-5-(2-fluoro-4-iodophen¡lamino)-8methyl¡lp¡ ndo[2,3-d]pyrimidin-4,7(3H,8H)-dione (TAK-733), or a pharmaceutically acceptable salt thereof, and an EGFR inhibitor selected from cetuximab, panitumumab, osimertinib, erlotinib, gefitinib, necitumumab, neratinib, lapatinib, vandetanib and brigatinib. In one embodiment, the subject is pretreated with surgery and pretreated with a BRAF inhibitor selected from encorafenib, dabrafenib and vemurafenib, or a pharmaceutically acceptable salt thereof, a MEK inhibitor selected from binimetinib. , trametinib and cobimetinib, or a pharmaceutically acceptable salt thereof, and an EGFR inhibitor selected from cetuximab and panitumumab. In one embodiment, colorectal cancer became resistant 105 to said prior treatment. In one embodiment, the subject developed brain metastasis during said prior treatment. In some embodiments, a subject having a BRAF-associated metastatic non-small cell lung cancer (e.g., a BRAF mutant metastatic non-small cell lung cancer) has received treatment with one or more EGFR inhibitors. prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In one embodiment, the subject was pretreated with one or more EGFR inhibitors independently selected from cetuximab, panitumumab, osimertinib, erlotinib, gefitinib, necitumumab, neratinib, lapatinib, vandetanib, and brigatinib. In one embodiment, the subject was pretreated with erlotinib. In one embodiment, the subject was pretreated with gefitinib. In one embodiment, the subject was pretreated with erlotinib and gefitinib. In one embodiment, non-small cell lung cancer became resistant to such prior treatment. In one embodiment, the subject developed brain metastasis during said prior treatment. In some embodiments, a subject having BRAF-associated metastatic non-small cell lung cancer has received treatment with a BRAF inhibitor other than a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. from a pharmaceutical point of view of this. In one embodiment, the subject was pretreated with a BRAF inhibitor selected from encorafenib, dabrafenib, vemurafenib, N-[3(5-chloro-lH-pyrrolo[2,3-b]pyridín -3-¡lcarbon¡l)-2,4-difluorophen¡l]propan-l-sulfonamide (PLX4720) and (3R)-N-(3-[[5-(2-cycloprop¡ lp¡r¡midín-5-¡l)-lH-pyrrolo[2,3-b]pyridin-3-¡l]carbon¡l]-2,4-difluorophen¡l)-3fluoropyrrolidin-l -sulfonamide (PLX8394), or a pharmaceutically acceptable salt thereof, a MEK inhibitor selected from binimetinib, trametinib, cobimetinib, selumetinib, pimasertib, refametinib, mirdametinib, 2-(2-chloro-4-iodophenylam, no)-N-(cyclopropylmethoxy¡)-3,4difluorobenzamide (CI-1040) and 3-[2(R),3-dihydroxy¡propyl]-6-fluoro-5-(2-fluoro-4 -iodofen¡lam¡no)-8met¡lp¡r¡do[2,3-d]p¡r¡m¡d¡n-4,7(3H,8H)-d¡one (TAK-733), or a pharmaceutically acceptable salt thereof, and an EGFR inhibitor selected from cetuximab, panitumumab, osimertinib, erlotinib, gefitinib, necitumumab, neratinib, lapatinib, vandetanib and brigatinib. In one embodiment, the subject was pretreated with a BRAF inhibitor selected from vemurafenib, dabrafenib and encorafenib, or a pharmaceutically acceptable salt thereof, and an EGFR inhibitor selected from cetuximab and panitumumab prior to treatment. with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In one embodiment, lung cancer 106 non-small cells became resistant to said pretreatment. In one embodiment, the subject developed brain metastasis during said prior treatment. In some embodiments, a subject who has a BRAF-associated metastatic thyroid cancer (e.g., a BRAF-mutant metastatic thyroid cancer) has received treatment with a BRAF inhibitor (i.e., a BRAF inhibitor other than a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof) prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In one embodiment, the subject was pretreated with a BRAF inhibitor selected from encorafenib, dabrafenib, vemurafenib, N-[3-(5-chloro-lH-pyrrolo[2,3-b]pyrídin3- ¡lcarbonyl)-2,4-difluorophen¡l]propan-l-sulfonamide (PLX4720) and (3R)-N-(3-[[5-(2-cycloprop¡lp¡rim¡d¡n5) -¡l)-lH-pyrrolo[2,3-b]pyr¡din-3-yl]carbonyl]-2,4-difluorophen¡l)-3-fluorop¡rrol¡d n-l-sulfonamide (PLX8394), or a pharmaceutically acceptable salt thereof, a MEK inhibitor selected from binimetinib, trametinib, cobimetinib, selumetinib, pimasertib, refametinib, mirdametinib, 2-(2-chloro- 4-iodophenylamino)-N-(cyclopropylmethoxy)-3,4-difluorobenzamide (CI-1040) and 3-[2(R),3-d¡hydroxy¡prop¡l]-6-fluoro-5 -(2-fluoro-4-iodofen¡lano)-8-met¡lp¡r¡do[2,3-d]pyrimid¡n4,7(3H,8H)-dione (TAK-733) , or a pharmaceutically acceptable salt thereof, and an EGFR inhibitor selected from cetuximab, panitumumab, osimertinib, erlotinib, gefitinib, necitumumab, neratinib, lapatinib, vandetanib and brigatinib. In one embodiment, the subject was pretreated with a BRAF inhibitor selected from vemurafenib, dabrafenib and encorafenib prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt of this. In one embodiment, the thyroid cancer became resistant to said prior treatment. In one embodiment, the subject developed brain metastasis during said prior treatment. In one embodiment, the subject has a BRAF-associated LMD and was previously treated with a BRAF inhibitor (e.g., a BRAF inhibitor other than a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof) and one or more checkpoint inhibitors (e.g., any of the checkpoint inhibitors disclosed herein, e.g., an inhibitor of CTLA4, a PD-1 inhibitor and / or a PD-L1 inhibitor) before treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a salt acceptable from the pharmaceutical point of view of this. In one embodiment, the subject was pretreated with a BRAF inhibitor selected from encorafenib, dabrafenib, vemurafenib, N-[3-(5-chloro-lHpyrrolo[2,3-b]pyridin-3- ilcarbon¡l)-2,4-difluorophen¡l]propan-l-sulfonamide (PLX4720) and (3R)-N-(3-[[5(2-c¡cloprop¡lp¡r¡m¡d) ¡n-5-¡l)-lH-pyrrolo[2,3-b]pyridín-3-¡l]carbon¡l]-2,4-difluorophen¡l)-3- fluoroprolide-l 107 sulfonamide (PLX8394), or a pharmaceutically acceptable salt thereof, and one or more checkpoint inhibitors independently selected from ipilimumab, nivolumab, pembrolizumab and avelumab. In one embodiment, the LMD became resistant to said pretreatment. In one embodiment, the subject has a BRAF-associated LMD and was previously treated with a BRAF inhibitor (e.g., a BRAF inhibitor other than a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof), a MEK inhibitor, and one or more checkpoint inhibitors (e.g., any of the checkpoint inhibitors disclosed herein , for example, a CTLA-4 inhibitor, a PD-1 inhibitor and / or a PD-L1 inhibitor) prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In one embodiment, the subject was pretreated with a BRAF inhibitor selected from encorafenib, dabrafenib, vemurafenib, N-[3(5-chloro-lH-pyrrolo[2,3-b]pyridín -3-¡lcarbon¡l)-2,4-difluorophen¡l]propan-l-sulfonamide (PLX4720) and (3R)-N-(3-[[5-(2-cycloprop¡lp¡ rimidin-5-yl)-lH-pyrrolo[2,3-b]pyridin-3-yl]carbonyl]-2,4-difluorophenyl)-3fluoropyrrolidin-l-sulfonamide (PLX8394), or a commercially acceptable salt pharmaceutical view of these, a MEK inhibitor selected from binimetinib, trametinib, cobimetinib, selumetinib, pimasertib, refametinib, mirdametinib, 2-(2-chloro-4-iodophenylamino)-N-(cycloprop¡lmethox¡)-3,4difluorobenzamide ( CI-1040) and 3-[2(R),3-dihydroxy¡propyl]-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8methylpyride[2,3- d]p¡r¡m¡din-4,7(3H,8H)-d¡one (TAK-733), or a pharmaceutically acceptable salt thereof, and a checkpoint inhibitor (e.g. For example, any of the checkpoint inhibitors disclosed herein, for example, a CTLA-4 inhibitor, a PD-1 inhibitor and / or a PD-L1 inhibitor). In one embodiment, the subject was pretreated with a BRAF inhibitor selected from encorafenib, dabrafenib and vemurafenib, or a pharmaceutically acceptable salt thereof, a MEK inhibitor selected from binimetinib, trametinib and cobimetinib, or a pharmaceutically acceptable salt thereof, and one or more checkpoint inhibitors independently selected from ipilimumab, nivolumab, pembrolizumab and avelumab. In one embodiment, the LMD became resistant to said prior treatment. In one embodiment, the subject has a BRAF-associated LMD and was previously treated with one or more checkpoint inhibitors (e.g., any of the checkpoint inhibitors disclosed herein, e.g., a CTLA-4 inhibitor, a PD-1 inhibitor and / or a PD-L1 inhibitor) prior to treatment with a compound of Formula I, Formula ΙΑ, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt of this. In one embodiment, the subject was pretreated with one or more 108 independently selected checkpoint inhibitors of ipilimumab, nivolumab, pembrolizumab, avelumab and RN888. In one embodiment, the LMD became resistant to said prior treatment. In one embodiment, the subject has a BRAF-associated glioma and was previously treated with surgery prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or an acceptable salt. from the pharmaceutical point of view of this. In one embodiment, the glioma became resistant to said pretreatment. In one embodiment, the glioma is a grade 2, grade 3 or grade 4 glioma. In one embodiment, the subject has a BRAF-associated glioma and was previously treated with radiotherapy (e.g., whole brain radiotherapy or stereotactic radiosurgery) prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In one embodiment, the glioma became resistant to said pretreatment. In one embodiment, the glioma is a grade 2, grade 3 or grade 4 glioma. In one embodiment, the subject has a BRAF-associated glioma and was previously treated with one or more cytotoxic chemotherapeutic agents prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V , or a pharmaceutically acceptable salt thereof. In one embodiment, the subject was pretreated with one or more cytotoxic chemotherapeutic agents independently selected from cisplatin, pemetrexed, vinorelbine, and paclitaxel. In one embodiment, the glioma became resistant to said pretreatment. In one embodiment, the glioma is a grade 2, grade 3 or grade 4 glioma. In one embodiment, the subject has a BRAF-associated glioma and was previously treated with an ornithine decarboxylase inhibitor prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In one embodiment, the subject was previously treated with an ornithine decarboxylase inhibitor that is eflornithine (as the racemate, or the D or L enantiomer). In one embodiment, the glioma became resistant to said pretreatment. In one embodiment, the glioma is a grade 2, grade 3 or grade 4 glioma. In one embodiment, the subject has a BRAF-associated glioma and was previously treated with an alkylating agent prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt of this. In one embodiment, the subject was previously treated with an alkylating agent selected from temozolomide, lomustine and carmustine. In one embodiment, the glioma became resistant to said pretreatment. In one embodiment, the glioma is a 109 grade 2, grade 3 or grade 4 glioma. In one embodiment, the subject has a BRAF-associated glioma and was pretreated with an alkylating agent and an ornithine decarboxylase inhibitor prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In one embodiment, the subject was previously treated with an alkylating agent selected from temozolomide, lomustine and carmustine, and an ornithine decarboxylase inhibitor that is eflornithine (as the racemate, or the D or L enantiomer). In one embodiment, the glioma became resistant to said pretreatment. In one embodiment, the glioma is a grade 2, grade 3 or grade 4 glioma. In one embodiment, the subject has a BRAF-associated glioma and was previously treated with radiotherapy (e.g., whole brain radiotherapy or stereotactic radiosurgery) and an alkylating agent prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In one embodiment, the subject was previously treated with radiotherapy (e.g., whole brain radiotherapy or stereotactic radiosurgery) and an alkylating agent selected from temozolomide, lomustine, and carmustine. In one embodiment, the subject became resistant to said prior treatment. In one embodiment, the glioma is a grade 2, grade 3 or grade 4 glioma. In one embodiment, the subject has a BRAF-associated glioma and was previously treated with antibody treatment prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt of this. In one embodiment, the subject was previously treated with an antibody treatment that is bevacizumab. In one embodiment, the glioma became resistant to said pretreatment. In one embodiment, the glioma is a grade 2, grade 3 or grade 4 glioma. In one embodiment, the subject has a BRAF-associated glioma and was previously treated with surgery and radiation therapy prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt of this. In one embodiment, the glioma became resistant to said pretreatment. In one embodiment, the glioma is a grade 2, grade 3 or grade 4 glioma. In one embodiment, the subject has a BRAF-associated glioma and was previously treated with surgery, radiation therapy and an alkylating agent prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In one embodiment, the subject was pretreated with surgery, radiation therapy (e.g., whole brain radiation therapy or stereotactic radiosurgery), and an iviA / a / zuzz / u i o i u □ agent. 110 alkylating agent selected from temozolomide, lomustine and carmustine. In one embodiment, the glioma became resistant to said pretreatment. In one embodiment, the glioma is a grade 2, grade 3 or grade 4 glioma. In one embodiment, the subject has a BRAF-associated glioma and was previously treated with a BRAF inhibitor (i.e., a BRAF inhibitor other than a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof) prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. pharmaceutical point of view of this. In one embodiment, the subject was previously treated with a BRAF inhibitor selected from N-[3-(5-chloro-lH-pyrrolo[2,3-b]pyridin-3-ylcarbon l)-2,4difluorophenyl]propan-l-sulfonamide (PLX4720), vemurafenib, dabrafenib, encorafenib and (3R)-N-(3-[[5(2-cyclopropylpyrimidin-5-yl)-lH-pyrrolo[2, 3-b]pyridin-3-yl]carbonyl]-2,4-difluorophenyl)-3-fluoropyrrolidin-lsulfonamide (PLX8394). In one embodiment, the glioma became resistant to said pretreatment. In one embodiment, the glioma is a grade 2, grade 3 or grade 4 glioma. In one embodiment, the subject has a BRAF-associated glioma and was previously treated with a BRAF inhibitor (i.e., a BRAF inhibitor other than a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof) and a MEK inhibitor prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt of this. In one embodiment, the subject was previously treated with a BRAF inhibitor selected from N-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridín-3ylcarbonyl)-2,4-d fluorophen¡l]propan-l-sulfonamide (PLX4720), vemurafenib, dabrafenib, encorafenib and (3R)-N-(3-[[5-(2-cyclopropylpyrimidín-5-yl) -lH-pyrrolo[2,3-b]pyridin-3-¡l]carbon¡l]-2,4-difluorophen¡l)-3fluoropyrrolidin-l-sulfonamide (PLX8394) and a MEK inhibitor selected from binimetinib , trametinib, cobimetinib, selumetinib, pimasertib, refametinib, mirdametinib, 2-(2-chloro-4iodophenylamino)-N-(cyclopropílmethox¡)-3,4-difluorobenzamide (CI-1040) and 3-[2(R) ,3-dihydrox¡prop¡l]-6fluoro-5-(2-fluoro-4-iodofen¡lano)-8-met¡lprído[2,3-d]pyramid¡ n-4,7(3H,8H)-dione (TAK-733). In one embodiment, the subject was pretreated with a BRAF inhibitor selected from encorafenib, dabrafenib and vemurafenib, or a pharmaceutically acceptable salt thereof, and a MEK inhibitor selected from binimetinib, trametinib and cobimetinib, or a pharmaceutically acceptable salt thereof. In one embodiment, the glioma became resistant to said pretreatment. In one embodiment, the glioma is a grade 2, grade 3 or grade 4 glioma. In one embodiment, the subject has a BRAF-associated brainstem ganglioglioma and was previously treated with a BRAF inhibitor (i.e., a BRAF inhibitor other than a 111 compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof) prior to treatment with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In one embodiment, the subject was pretreated with a BRAF inhibitor selected from encorafenib, dabrafenib, vemurafenib, N-[3-(5-chloro-lHp¡rrolo[2,3-b]p¡nd¡n- 3-¡lcarbonyl)-2,4-difluorophen¡l]propan-l-sulfonamide (PLX4720) and (3R)-N-(3-[[5(2-cyclopropylpyrimidín-5-yl) -1H-pyrrolo[2,3-b]pindin-3-yl]carbonyl]-2,4-difluorophenyl)-3-fluoropírrolidine-lsulfonamide (PLX8394), or a commercially acceptable salt pharmaceutical view of these. In one embodiment, the subject was pretreated with a BRAF inhibitor selected from encorafenib, dabrafenib and vemurafenib, or a pharmaceutically acceptable salt thereof. In one embodiment, the ganglioglioma became resistant to said prior treatment. Although the genetic basis of tumorigenesis may vary between different cancer types, the cellular and molecular mechanisms required for metastasis appear to be similar in all solid tumor types. During a metastatic cascade, cancer cells lose growth inhibitory responses, experience alterations in adhesiveness, and produce enzymes that can degrade extracellular matrix components. This leads to detachment of tumor cells from the original tumor, infiltration into the circulation through the newly formed vasculature, migration, and extravasation of tumor cells to favorable distant sites where they can form colonies. Several genes have been identified as promoters or inhibitors of metastasis. Accordingly, methods are also provided herein for treating, inhibiting, preventing, assisting in the prevention or decreasing the symptoms of metastasis of a BRAF-associated cancer in a subject in need thereof, wherein the method comprises administering to the subject an amount therapeutically effective compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. In some embodiments, the compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, is used in combination with another antineoplastic treatment, for example, surgery (e.g., at least partial resection of a tumor) and / or radiation therapy and / or treatment with an antineoplastic agent. In one embodiment, the cancer is metastatic cancer with brain metastasis and the method comprises administering a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a technically acceptable salt pharmacist of this. In one embodiment, the cancer is metastatic melanoma with brain metastasis. In one embodiment, the cancer is metastatic colorectal cancer with brain metastasis. In one embodiment, the cancer is metastatic non-small cell lung cancer with metastases. 112 cerebral. In one embodiment, the cancer is metastatic ovarian cancer with brain metastasis. In one embodiment, the cancer is metastatic thyroid cancer with brain metastasis. In one embodiment, the cancer is neuroblastoma with brain metastasis and the method comprises administering a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt of this. In one embodiment, the subject was previously treated with another antineoplastic treatment, for example, surgery (e.g., at least partial resection of a tumor) and / or radiation therapy and / or treatment with an antineoplastic agent. In one embodiment, the subject became resistant to said prior treatment. In one embodiment, the subject is treated with a compound of Formula I, Formula ΙΑ, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, in combination with another antineoplastic treatment, for example, surgery (e.g., at least partial resection of a tumor) and / or radiotherapy and / or treatment with an antineoplastic agent. Also provided herein are methods of inhibiting metastasis in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. In some embodiments, the compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, is used in combination with another antineoplastic treatment, for example, surgery (for example, at least partial resection of a tumor) and / or radiotherapy and / or treatment with an antineoplastic agent. In one embodiment, the cancer is metastatic cancer with brain metastasis. In one embodiment, the cancer is metastatic melanoma with brain metastasis. In one embodiment, the cancer is metastatic colorectal cancer with brain metastasis. In one embodiment, the cancer is metastatic non-small cell lung cancer with brain metastasis. In one embodiment, the cancer is metastatic ovarian cancer with brain metastasis. In one embodiment, the cancer is metastatic thyroid cancer with brain metastasis. In one embodiment, the cancer is neuroblastoma with brain metastasis. In one embodiment, the subject was previously treated with another antineoplastic treatment, for example, surgery (e.g., at least partial resection of a tumor) and / or radiation therapy and / or treatment with an antineoplastic agent. In one embodiment, the subject became resistant to said prior treatment. In one embodiment, the subject is treated with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, in combination with another antineoplastic treatment, for example, surgery (e.g., at least partial resection of a tumor) and / or radiotherapy and / or treatment with an additional antineoplastic agent. 113 In one embodiment, the additional antineoplastic treatment is an antineoplastic agent. In one embodiment, the additional antineoplastic agent is selected from MEK inhibitors, BRAF inhibitors, EGFR inhibitors, HER2 and / or HER3 inhibitors, Axl inhibitors, PI3K inhibitors, SOS1 inhibitors, pathway inhibitors. signal transduction, checkpoint inhibitors, apoptotic pathway modulators, cytotoxic chemotherapeutic agents, therapeutics targeting angiogenesis and agents targeting the immune system. In one embodiment, the additional antineoplastic agent is a MEK inhibitor. In one embodiment, the MEK inhibitor is binimetinib, trametinib, cobimetinib, or a pharmaceutically acceptable salt thereof. In one embodiment, the MEK inhibitor is binimetinib, or a pharmaceutically acceptable salt thereof. As used herein, the term "treat metastases" means to reduce the size, progression and / or further spread of one or more metastases. Also provided herein are methods of inhibiting metastasis in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof or a pharmaceutical composition thereof. In some embodiments, the compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, is used in combination with another antineoplastic treatment, for example, surgery (e.g., at least partial resection of a tumor) and / or radiation therapy and / or treatment with an antineoplastic agent. In one embodiment, the cancer is metastatic cancer with brain metastasis. In one embodiment, the cancer is metastatic melanoma with brain metastasis. In one embodiment, the cancer is metastatic colorectal cancer with brain metastasis. In one embodiment, the cancer is metastatic non-small cell lung cancer with brain metastasis. In one embodiment, the cancer is metastatic ovarian cancer with brain metastasis. In one embodiment, the cancer is metastatic thyroid cancer with brain metastasis. In one embodiment, the cancer is neuroblastoma with brain metastasis. In one embodiment, the subject was previously treated with another antineoplastic treatment, for example, surgery (e.g., at least partial resection of a tumor) and / or radiation therapy and / or treatment with an antineoplastic agent. In one embodiment, the subject became resistant to said prior treatment. In one embodiment, the subject is treated with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, in combination with another antineoplastic treatment, for example, surgery (for example, at least partial resection of a tumor) and / or radiotherapy and / or treatment with an antineoplastic agent. In one embodiment, the antineoplastic treatment is an antineoplastic agent. In a way of 114 embodiment, the antineoplastic agent is selected from MEK inhibitors, BRAF inhibitors, EGFR inhibitors, HER2 and / or HER3 inhibitors, Axl inhibitors, PI3K inhibitors, SOS1 inhibitors, signal transduction pathway inhibitors, checkpoint inhibitors, apoptotic pathway modulators, cytotoxic chemotherapeutic agents, therapeutics targeting angiogenesis and agents targeting the immune system. In one embodiment, the antineoplastic agent is a MEK inhibitor. In one embodiment, the MEK inhibitor is binimetinib, trametinib, cobimetinib, or a pharmaceutically acceptable salt thereof. In one embodiment, the MEK inhibitor is binimetinib, or a pharmaceutically acceptable salt thereof. As used herein, the term "inhibit metastases" means to reduce the appearance (or recurrence) of one or more metastases, to prevent the appearance (or recurrence) of one or more metastases, or to reduce the spread of one or more metastases. Also provided are methods of decreasing the risk of developing one or more metastases or one or more additional metastases in a subject having a BRAF-associated cancer, including: selecting or identifying a subject with BRAF-associated cancer, or diagnosing such cancer. a subject, and administering a therapeutically effective amount of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, to the selected, identified subject or diagnosed as having a BRAF-associated cancer. Also provided are methods of decreasing the risk of developing one or more metastases or one or more additional metastases in a subject having a BRAF-associated cancer that includes administering a therapeutically effective amount of a compound of Formula I, Formula I-A, Formula II , Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, to a subject having a BRAF-associated cancer. The decreased risk of developing one or more metastases or one or more additional metastases in a subject who has a BRAF-associated cancer may be compared to the risk of developing one or more metastases or one or more additional metastases in the subject before treatment, or be compared to a subject or a population of subjects who have the same or similar BRAF-associated cancer and who have received no treatment or who have received a different treatment. The phrase "risk of developing one or more metastases" means the risk that a subject or subject who has a primary tumor will develop an additional tumor (e.g., a solid tumor) at a site distant from a primary tumor in a subject over the course of a period of time. a certain period of time, where the additional tumor includes the same or similar cancer cells as the primary tumor. Described herein are methods for reducing the risk of developing one or more metastases in a subject or subject having a cancer. The phrase risk of developing additional metastases means the risk that a subject or 115 subject who has a primary tumor and one or more additional tumors at sites distant from the primary tumor (where the one or more additional tumors include the same or similar cancer cells as the primary tumor) develops one or more additional tumors distant from the primary tumor , where the additional tumors include the same or similar cancer cells as the primary tumor. Methods to reduce the risk of developing additional metastases are described herein. Also provided herein is a method of treating a BRAF-associated tumor, metastasis of a BRAF-associated tumor, or a combination thereof, in a subject in need thereof, wherein the method comprises administering to the subject a compound of the Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In one embodiment, the subject has at least one metastasis or is at risk of developing at least one metastasis. In one embodiment, the subject has at least one metastasis. In one embodiment, the subject is at risk of developing at least one metastasis. In one embodiment, the subject is at risk of developing at least one metastasis, wherein said subject has a cancer selected from melanoma, colorectal cancer, thyroid cancer, non-small cell lung cancer, or ovarian cancer. In one embodiment, the cancer is a cancer that has a BRAF class I mutation (e.g., a BRAF V600 mutant cancer, e.g., a cancer that has a BRAF V600E and / or BRAF V600K mutation). ). In one embodiment, the cancer is a cancer that has a BRAF class II mutation (e.g., a G469A mutation or a BRAF V600E splice variant). In one embodiment, the subject was previously treated with another antineoplastic treatment, for example, surgery (e.g., at least partial resection of a tumor) and / or radiation therapy and / or treatment with an antineoplastic agent. In one embodiment, the subject became resistant to said prior treatment. In one embodiment, the subject is treated with a compound of Formula I, Formula ΙΑ, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, in combination with another antineoplastic treatment, for example, surgery (for example, at least partial resection of a tumor) and / or radiotherapy and / or treatment with an antineoplastic agent. In one embodiment, the antineoplastic treatment is an antineoplastic agent selected from MEK inhibitors, BRAF inhibitors, EGFR inhibitors, SOS1 inhibitors, HER2 and / or HER3 inhibitors, Axl inhibitors, PI3K inhibitors, signal transduction pathway, checkpoint inhibitors, apoptotic pathway modulators, cytotoxic chemotherapeutic agents, therapeutics targeting angiogenesis and agents targeting the immune system. In one embodiment, the antineoplastic agent is a MEK inhibitor. In one embodiment, the MEK inhibitor is binimetinib, trametinib, cobimetinib, or a pharmaceutically acceptable salt thereof. In one embodiment, the MEK inhibitor is binimetinib, or a pharmaceutically acceptable salt thereof. 116 In some embodiments, a subject is administered one or more agents to ameliorate the side effects of treatment (e.g., one or more of corticosteroids, serotonin antagonists, dopamine antagonists, NK-1 inhibitors, cannabinoids, drugs antianxiety (e.g., lorazepam or diazepam), antibiotics, antifungal agents, colony-stimulating factor, iron supplements, Procrit, epoetin alfa, darbepoetin alfa, antiemetics, diuretics, NSAIDs, pain relievers, methotrexate, antidiuretics, probiotics, medications for blood pressure, anti-nausea agents, laxatives, etc.). In one embodiment, the BRAF-associated tumor is a benign tumor, and a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a commercially acceptable salt, may be used. pharmaceutical view of this, alone or in combination with one or more different forms of treatment to treat a subject with a benign tumor. In some embodiments, a subject has a CNS tumor and receives one or more agents to improve one or more symptoms associated with a CNS tumor, including, but not limited to, seizures, nausea, headaches, blurred vision, vision loss, loss of balance, changes in fine motor skills and drowsiness. Examples of such agents for improving one or more symptoms associated with a CNS tumor include corticosteroids, anticonvulsant medications (e.g., cannabidiol, gabapentin, or pregabalin), analgesics (e.g., NSAIDs, acetaminophen), and anti-nausea agents. Also provided is a method of inhibiting BRAF kinase activity in a mammalian cell, comprising contacting the cell with an effective amount of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In some embodiments, the contacting is in vitro. In some embodiments, contacting is in vivo. In some embodiments, the contacting is in vivo, where the method comprises administering a therapeutically effective amount of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a salt acceptable from the pharmaceutical point of view of this, to a subject that has a cell that has BRAF kinase activity. In some embodiments, the cell is a cancer cell. In some embodiments, the cancer cell is from any cancer described herein. In some embodiments, the cancer cell is a BRAF-associated cancer cell. In some embodiments, the cell is a brain cell (e.g., a neuronal cell or a glial cell). As used herein, the term "contacting" or "contacting" refers to bringing together the indicated portions in an in vitro system or an in vivo system. For example, contacting a BRAF kinase with a compound provided herein includes contacting a cell containing a BRAF kinase with the compound provided herein, as well as, 117 for example, introducing a compound provided herein into a sample containing a cellular or purified preparation containing BRAF kinase. Also provided herein is a method of inhibiting cell proliferation, in vitro or in vivo, wherein the method comprises contacting a cell with a therapeutically effective amount of a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof as defined herein. As used herein, a therapeutically effective amount of a compound, pharmaceutical composition thereof, or pharmaceutical combination thereof, is an amount sufficient to achieve any one or more beneficial or desired results. For prophylactic use, beneficial or desired outcomes include eliminating or reducing the risk, decreasing the severity, or delaying the onset of the disease, including biochemical, histological, and / or behavioral symptoms of the disease, its complications, and intermediate pathological phenotypes that occur during the development of the disease. For therapeutic use, beneficial or desired results include providing a therapeutic effect, which may include reducing the size of a tumor, inhibiting (e.g., slowing down, to some extent, preferably stopping) tumor progression, inhibiting (e.g., slowing , to some extent, preferably stop) tumor growth, inhibit (e.g., slow down, to some extent, preferably stop) tumor invasiveness, and / or inhibit (e.g., slow down, to some extent, preferably stop) tumor metastasis . The mid-level skilled person understands that tumor progression in human subjects can be determined with various methods. For example, the size of a tumor close to the skin can be measured by establishing the width and depth of the tumor with calipers and then calculating the tumor volume. Less accessible tumors, such as lung and CNS cancers, can be measured by looking at images obtained with magnetic resonance imaging (MRI). CNS tumors, such as brain tumors, can be measured with a combination of MRI and neurological performance monitoring. Brain tumor growth is generally associated with decreased neurological performance. Providing a therapeutic effect also includes prolonging the survival of a subject beyond that expected in the absence of treatment and / or alleviating to some degree (or preferably eliminating) one or more signs or symptoms associated with cancer. In one embodiment, treatment of a subject with a compound or combination according to an invention prolongs survival beyond that expected in the absence of treatment at a rate of 1 or more months, for example, at a rate of 3 or more. months, for example, at a rate of 6 or more months, for example, at a rate of 1 or more years, for example, at a rate of 2 or more years, for example, at a rate of 3 or more years, for example, at at a rate of 5 or more years, for example, at a rate of 10 or more years. Providing a therapeutic effect also includes reducing the number of cancer cells. iviA / a / zuzz / u i o i u □ 118 Providing a therapeutic effect also includes killing cancer cells. Providing a therapeutic effect also includes reducing tumor mass. Providing a therapeutic effect also includes causing remission of a cancer. A therapeutically effective amount may be administered in one or more administrations. For the purposes of the present invention, a therapeutically effective amount as a dose of a compound, or a pharmaceutical composition thereof, is an amount sufficient to achieve prophylactic or therapeutic treatment either directly or indirectly. As understood in the clinical context, a therapeutically effective amount as a dose of a compound or pharmaceutical composition thereof may be achieved in conjunction with another treatment. Therefore, a therapeutically effective amount may be considered in the context of administering one or more treatments (for example, one or more antineoplastic agents), and the administration of a single agent in a therapeutically effective amount may be considered if, in conjunction with one or more other agents, a desirable result is or can be achieved. In reference to cancer treatment, a therapeutically effective amount may also refer to the amount that has the effect of (1) reducing the size of the tumor, (2) inhibiting (i.e., slowing to some extent, preferably stopping) the appearance of tumor metastases, (3) inhibit to some degree (i.e., slow to some degree, preferably stop) tumor growth or tumor invasiveness, and / or (4) alleviate to some degree (or, preferably, eliminate) one or more signs or symptoms associated with cancer. The therapeutic or pharmacological efficacy of doses and administration regimens can also be characterized as the ability to induce, improve, maintain or prolong disease control and / or overall survival in subjects with these specific tumors, which can be measured as a Prolonging the time before disease progression. In one embodiment, a subject treated in accordance with any of the methods disclosed herein may be evaluated according to one or more standard response evaluation criteria known in the art, including RECIST (Response Evaluation Criteria in Solid Tumors). , for example, RECIST version 1.0, RECIST version 1.1, and modified RECIST 1.1 (mRECIST 1.1), RANO-BM (Response Evaluation in Neuro-Oncology of Brain Metastases), Macdonald, RANO-LMD, and NANO (Neurological Evaluation in Neuro-Oncology). In one embodiment of any of said criteria, the tumor is evaluated by an imaging study (e.g., magnetic resonance imaging, computed tomography, multidetector computed tomography, or positron emission tomography). In one embodiment, the response to treatment is evaluated according to RECIST version 1.1, where: complete response (CR) is defined as the complete disappearance of all tumor lesions; Partial response (PR) is defined as a reduction in the sum of tumor measurements of at least 30%; progressive disease (PD) is defined as an increase of at least 20% in the sum of tumor measurements (where the development of new lesions or substantial progression of non-target lesions is also defined as PD), in 119 where an increase of at least 5 mm compared to the baseline level is evaluated as PD; and stable disease (SD) is defined as neither sufficient reduction to be classified as PR nor sufficient increase to be classified as PD, taking as reference the diameters of the smallest sum during treatment. In one embodiment, the evaluations include intracranial response (assessed according to modified RECIST with gadolinium-enhanced MRI), extracranial response, overall response rate, disease control rate (DCR), duration of response (DOR), progression-free survival (PFS) and overall survival (OS). In one embodiment, the subject has a CNS tumor and has at least one measurable intracranial tumor. In one embodiment, the at least one measurable intracranial tumor is measured by magnetic resonance imaging and computed tomography. A measurable tumor (tumor lesion) means a tumor that can be accurately measured in at least one dimension (the widest diameter in the measurement plane is not recorded) with a minimum size of: 10 mm by computed tomography (slice thickness of computed tomography no larger than 5 mm); measurement with 10 mm caliper by clinical examination; 20 mm by chest X-ray. When used as a pharmaceutical product, a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, may be administered in the form of pharmaceutical compositions. These compositions can be prepared in a manner known in the pharmaceutical art, and can be administered by various routes, depending on whether local or systemic treatment is desired and depending on the area to be treated. Administration may be topical (including transdermal, epidermal, ophthalmic and to mucous membranes, including intranasal, vaginal and rectal administration), pulmonary (for example, by inhalation or insufflation of powders or aerosols, including by nebulizer; intratracheal or intranasal), oral or parenteral. Oral administration may include a dosage form formulated for once-daily or twice-daily (BID) administration. Parenteral administration includes intravenous, intra-arterial, subcutaneous, intraperitoneal or intramuscular administration or injection or infusion; or intracranial administration, for example, intrathecal or intraventricular. Parenteral administration may be in the form of a single bolus dose or may be, for example, by means of a continuous infusion pump. Pharmaceutical compositions and formulations for topical administration may include transdermal patches, ointments, lotions, creams, gels, drops, suppositories, aerosols, liquids and powders. Conventional pharmaceutical carriers, aqueous, powder or oil bases and thickeners, and the like, may be necessary or desirable. Also provided herein are pharmaceutical compositions containing, as the active ingredient, a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV 120 or Formula V, or a pharmaceutically acceptable salt thereof, in combination with one or more pharmaceutically acceptable carriers (excipients). For example, a pharmaceutical composition prepared with a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof. In some embodiments, the composition is suitable for topical administration. In making the compositions provided herein, the active ingredient is generally mixed with an excipient, diluted with an excipient, or enclosed within such a carrier in the form of, for example, a capsule, sachet, paper, or other container. . When the excipient serves as a diluent, it can be a solid, semisolid or liquid material, which acts as a vehicle, carrier or medium for the active ingredient. Thus, the compositions can be in the form of tablets, pills, powders, dragees, sachets, stamps, elixirs, suspensions, emulsions, solutions, syrups, aerosols (as a solid or in a liquid medium), ointments containing, for example, For example, up to 10% by weight of the active compound, soft and hard gelatin capsules, suppositories, sterile injectable solutions and sterile packaged powders. In some embodiments, the composition is formulated for oral administration. In some embodiments, the composition is a solid oral formulation. In some embodiments, the composition is formulated as a tablet or capsule. Also provided herein are pharmaceutical compositions containing a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, with a pharmaceutically acceptable carrier. the pharmaceutical point of view. Pharmaceutical compositions containing a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, can be prepared as the active ingredient by intimately mixing the compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, with a pharmaceutical carrier according to conventional pharmaceutical compounding techniques. The carrier can have a wide variety of forms depending on the desired route of administration (e.g., oral, parenteral). In some embodiments, the composition is a solid oral composition. Suitable pharmaceutically acceptable carriers are known in the art. Descriptions of some of these pharmaceutically acceptable carriers can be found in The Handbook of Pharmaceutical Excipients, published by the American Pharmaceutical Association and the Pharmaceutical Society of Great Britain. Methods for formulating pharmaceutical compositions have been described in numerous publications, such as Pharmaceutical Dosage Forms: Tablets, Second Edition, Revised and Expanded, volumes 1-3, edited by Lieberman et al., Pharmaceutical Dosage Forms: Parenteral 121 Medications, volumes 1-2, edited by Avis et ai.) and Pharmaceuticai Dosage Forms: Disperse Systems, volumes 1-2, edited by Lieberman et ai.·, published by Marcel Dekker, Inc. To prepare the compositions in oral dosage form, any of the usual pharmaceutical means can be used. Therefore, for liquid oral preparations, such as suspensions, elixirs and solutions, suitable carriers and additives include water, glycols, oils, alcohols, flavoring agents, preservatives, stabilizers, coloring agents and the like; For solid oral preparations, such as powders, capsules and tablets, suitable carriers and additives include starches, sugars, diluents, granulating agents, lubricants, binders, disintegrating agents and the like. Suitable binders include, but are not limited to, starch, gelatin, natural sugars, such as glucose or beta-lactose, corn sweeteners, natural and synthetic gums, such as acacia, tragacanth or sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride and the like. Disintegrants include, but are not limited to, starch, methylcellulose, agar, bentonite, xanthan gum and the like. Solid oral preparations may also be coated with substances such as sugars or enteric coated to modulate the primary site of absorption. For parenteral administration, the carrier will usually consist of sterile water, and other ingredients may be added to increase solubility or preservation. Injectable suspensions or solutions can also be prepared by using aqueous carriers together with suitable additives. The pharmaceutical compositions herein will contain, per unit dosage, for example, tablet, capsule, powder, injection, teaspoon and the like, an amount of the active ingredient necessary to administer a therapeutically effective amount described herein. Compositions comprising a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, may be formulated in a unit dosage form, wherein each dose contains about 5 to about 1000 mg (1 g), most often about 100 mg to about 500 mg, of the active ingredient. The term "unit dose form" refers to physically separate units suitable as unit doses for human subjects and other subjects, where each unit contains a predetermined amount of active material (i.e., a compound of Formula I, Formula I-A, Formula II , Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof) calculated to produce the desired therapeutic effect, in association with a suitable pharmaceutical excipient. In some embodiments, the compositions provided herein contain from about 5 mg to about 50 mg of the active ingredient. A person of mid-level skill will appreciate that this encompasses compounds or compositions containing from about 5 mg to about 10 mg, from about 10 mg to about 15 mg, from about 15 mg to about 122 from 20 mg, from about 20 mg to about 25 mg, from about 25 mg to about 30 mg, from about 30 mg to about 35 mg, from about 35 mg to about 40 mg, from about 40 mg to about 45 mg or about 45 mg to about 50 mg of the active ingredient. In some embodiments, the compositions provided herein contain from about 50 mg to about 500 mg of the active ingredient. A person of mid-level skill will appreciate that this encompasses compounds or compositions containing from about 50 mg to about 100 mg, from about 100 mg to about 150 mg, from about 150 mg to about 200 mg, from about 200 mg to about 250 mg, about 250 mg to about 300 mg, about 350 mg to about 400 mg or about 450 mg to about 500 mg of the active ingredient. In some embodiments, the compositions provided herein contain about 10 mg, about 20 mg, about 80 mg, or about 160 mg of the active ingredient. The daily dose of the compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, may vary in a wide range from 1.0 to 10,000 mg per adult human per day, or more, or any range in between. For oral administration, the compositions are preferably provided in the form of tablets containing 0.01, 0.05, 0.1, 0.5, 1.0, 2.5, 5.0, 10.0, 15, 0, 25.0, 50.0, 100, 150, 160, 200, 250 and 500 milligrams of the active ingredient for symptomatic adjustment of the dose to the subject to be treated. A therapeutically effective amount of the drug is usually administered at a dose level of about 0.1 mg / kg to about 1000 mg / kg body weight per day, or any range in between. Preferably, the range is from about 0.5 to about 500 mg / kg body weight per day, or any range in between. More preferably, from about 1.0 to about 250 mg / kg body weight per day, or any range in between. More preferably, from about 0.1 to about 100 mg / kg body weight per day, or any range in between. In an example, the range may be from about 0.1 to about 50.0 mg / kg body weight per day, or any amount or range in between. In another example, the range may be from about 0.1 to about 15.0 mg / kg body weight per day, or any range in between. In yet another example, the range may be from about 0.5 to about 7.5 mg / kg body weight per day, or any amount or range in between. Pharmaceutical compositions containing a compound of Formula I, Formula I-A, Formula II, Formula III, Formula IV or Formula V, or a pharmaceutically acceptable salt thereof, can be administered in a regimen of 1 to 4 times per day or at the rate of a single daily dose. The active compound can be effective over a wide dose range and is generally administered in a therapeutically effective amount. People in mid-level trades can 123 easily determine the optimal doses to be administered. Therefore, it will be understood that the amount of the compound actually administered will generally be determined by a physician, and will vary according to the relevant circumstances, including the mode of administration, the compound actually administered, the concentration of the preparation, the condition to be treated and the progression of the pathological condition. In addition, factors associated with the particular subject under treatment, including the subject's response, age, weight and diet, the timing of administration, and the severity of the subject's symptoms, will result in the need to adjust doses. In some embodiments, the compounds provided herein may be administered in an amount of about 1 mg / kg to about 100 mg / kg. In some embodiments, the compound provided herein may be administered in an amount of about 1 mg / kg to about 20 mg / kg, about 5 mg / kg to about 50 mg / kg, about 10 mg / kg to about 40 mg / kg, from about 15 mg / kg to about 45 mg / kg, from about 20 mg / kg to about 60 mg / kg or from about 40 mg / kg to around 70 mg / kg. For example, about 5 mg / kg, about 10 mg / kg, about about about about about about about mg / kg, about mg / kg, about mg / kg, about mg / kg, about mg / kg, mg / kg, mg / kg, about about about about mg / kg, about mg / kg, about mg / kg, about mg / kg, mg / kg, mg / kg, mg / kg, mg / kg, about 90 mg / kg, about 95 mg / kg or about 100 mg / kg. In some embodiments, such administration may be once-daily (QD) or twice-daily (BID) administration. In some embodiments, such administration may be on an intermittent dosing schedule. A person of mid-level skill will recognize that both in vivo and in vitro assays using suitable known and generally accepted cellular and / or animal models are predictive of the ability of a test compound to treat or prevent a given disorder. A mid-level skilled person will further recognize that human clinical trials, including first-in-human, dose-ranging and efficacy trials, in healthy subjects and / or those suffering from a given disorder, can be completed. according to methods known in clinical and medical technique. Provided herein are pharmaceutical kits that are useful, for example, in the treatment of BRAF-associated diseases or disorders, such as cancer, which include one or more containers containing a pharmaceutical composition comprising a therapeutically effective amount of a compound provided at the moment. If desired, such kits may further include one or more of various conventional pharmaceutical kit components, such as, for example, containers with one or more pharmaceutically acceptable carriers, additional containers, etc., as will be apparent to people in the mid-level trade. 124 Instructions, either as package inserts or labels, indicating the quantities of the components to be administered, guidelines for administration, and / or guidelines for mixing the components may also be included in the kit. The following embodiments are also provided herein: Embodiment 1. A compound of Formula I I or a pharmaceutically acceptable salt thereof, wherein: L is NH or O; R1 is C1-C6 alkyl, C1-C6 deuteroalkyl, C1-C6 fluoroalkyl, C3-C6 cycloalkyl, (C3-C6 cycloalkyl)CH2-, (C1-C6 alkoxy)Cl-C6 alkyl-, Ar1, ANCHE-, hetAr1or hetCyc1; Ar1 is phenyl which is optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from halogen and C1-C3 alkyl; hetAr1 is a 5-6 membered heteroaryl ring having 1 or 2 ring nitrogen atoms and which is optionally substituted with 1, 2 or 3 substituents independently selected from halogen and C1-C3 alkyl; hetCyc1 is a saturated 4-6 membered monocyclic heterocyclic ring having one ring oxygen atom; R2is -CH3, -CH2CH3, -CH=CH2, F, Cl, Br or CN; R3is F or Cl; R4is H or F; R5 is H, F or Cl; R6is C1-C6 alkyl, and R7is C1-C6 alkyl, hetCyc2o C3-C6 cycloalkyl, or R6and R7 together with the nitrogen atom to which they are attached form a saturated ring system selected from (i) a 4-6 membered monocyclic ring optionally having a second heteroatom of ring which is O, wherein said ring is optionally substituted with 1 or 2 substituents independently selected from F, -OH, -OCH3, -OCHF2, -OCD3, -CH3, -CH2CH3, -CH2OCH3, -CH2OCH2F, -CH2OCHF2, - CH2OCF3, -OCF3, -OCH2CH3, and CN, (i) a 6-7 membered fused bicyclic ring optionally substituted with 1 or 2 substituents independently selected from F and -CH3, (i¡) a 6-bridged ring -7 members and (iv) a 6-8 membered spirocyclic ring; and 125 hetCyc2 is a saturated 5-6 membered monocyclic heterocyclic ring having 1 or 2 ring heteroatoms independently selected from N and O; as long as the compound is not: N-(2-chloro-3-((3,5-dimethyl-4-oxo-3,4-dihydroqunazolin-6-yl)amino)-4-fluorophenyl)pyrrole d¡n-lsulfonamide, (R)-N-(2-chloro-3-((3,5-dimethyl-4-oxo-3,4-d¡hydroquinazolin-6-¡l)am¡ no)-4-fluorophenyl)-3fluoropyrrolidin-l-sulfonamide, or N-(2-chloro-3-((3,5-dimethyl-4-oxo-3,4-dihydroquinazolin-6-l)amino)-4 -fluorophenyl)-N-ethyl-Nmethylamino-l-sulfonamide. Embodiment 2. A compound of Formula II or a pharmaceutically acceptable salt thereof, wherein: L is NH or O; R1 is C1-C6 alkyl or C1-C6 fluoroalkyl; R2is -CH3, -CH2CH3, -CH=CH2, F, Cl, Br or CN; R3is F or Cl; R4is H or F; R5 is H, F or Cl; R6is C1-C6 alkyl, and R7is C1-C6 alkyl, hetCyc2o C3-C6 cycloalkyl, or R6and R7 together with the nitrogen atom to which they are attached form a saturated ring system selected from (i) a 4-6 membered monocyclic ring optionally having a second heteroatom of ring which is O, wherein said ring is optionally substituted with 1 or 2 substituents independently selected from F, -OH, -OCH3, -OCHF2, -OCD3, -CH3, -CH2CH3, -CH2OCH3, -CH2OCH2F, -CH2OCHF2, - CH2OCF3, -OCF3, -OCH2CH3, and CN, (ii) a 6-7 membered fused bicyclic ring optionally substituted with 1 or 2 substituents independently selected from F and -CH3, (i¡) a 6-bridged ring 7 members and (iv) a 6-8 membered spirocyclic ring; and hetCyc2 is a saturated 5-6 membered monocyclic heterocyclic ring having 1 or 2 ring heteroatoms independently selected from N and O; as long as the compound is not: 126 N-(2-chloro-3-((3,5-dimethyl-4-oxo-3,4-dihydroquinazolin-6-íl)amino)-4-fluoropheníl)pyrrolidine-lsulfonamide, (R) -N-(2-chloro-3-((3,5...

Claims

1. A compound that is N-(2-chloro-3-((5-chloro-3-methyl-4-oxo-3,4-dihydroquinazolin-6-1l)amino)-4-fluorophenyl)-3-fluoroazethidine-1-sulfonamide having the structure: or a pharmaceutically acceptable salt thereof.

2. A compound that is N-(2-chloro-3-((5-chloro-3-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)amino)-4-fluorophenyl)-3-fluoroazethidine-sulfonamide having the structure:

3. A pharmaceutical composition comprising a compound according to any one of claims 1 or 2, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers.

4. The use of a compound according to any of claims 1 or 2 or a pharmaceutically acceptable salt thereof for treating a BRAF-associated tumor in a subject in need.

5. The use as claimed in claim 4, wherein said BRAF-associated tumor has a BRAF class II mutation.

6. The use as claimed in claim 5, wherein said BRAF class II mutation is a non-V600 BRAF mutation.

7. The use as claimed in claim 6, wherein said non-V600 BRAF mutation is BRAF G469A or G469R.

8. The use as claimed in claim 5, wherein said BRAF class II mutation is a BRAF V600E splice variant.

9. The use as claimed in claim 8, wherein said BRAF V600E splice variant is p61BRAF(V600E).

10. The use as claimed in any of claims 4 to 9, wherein said BRAF-associated tumor is a cancer type selected from lung cancer, melanoma, colorectal cancer, breast cancer, pancreatic cancer, thyroid cancer, prostate cancer, adenoid cystic carcinoma, appendiceal cancer, small bowel cancer, squamous cell carcinoma of the head and neck, angiosarcoma, bladder carcinoma, plasma cell neoplasia, hepatopancreatobiliary carcinoma, ovarian carcinoma, neuroendocrine cancer, cholangiocarcinoma, and CNS cancer types.

11. The use as claimed in any of claims 4 to 10, wherein said cancer is a type of metastatic cancer.

12. The use as claimed in claim 11, wherein said cancer is a type of metastatic CNS cancer.

13. The use as claimed is any of claims 4 to 9, wherein said BRAF-associated tumor is a primary brain tumor.

14. The use as claimed in claim 13, wherein said primary brain tumor is a grade 2 glioma, grade 3 glioma or grade 4 glioma.

15. The use as claimed in claim 4, wherein said BRAF-associated tumor has a BRAF class I mutation.

16. The use as claimed in claim 15, wherein said BRAF class I mutation is BRAF V600E or BRAF V600K.

17. The use as claimed in claim 15 or 16, wherein said BRAF-associated tumor is selected from melanoma, colorectal cancer, thyroid cancer, non-small cell lung cancer, ovarian cancer, renal cell carcinoma and metastatic cancer types of these and primary brain tumors.

18. The use as claimed in any of claims 4 to 17, wherein the drug is adapted to be additionally administerable with additional antineoplastic therapy.

19. The use as claimed in claim 18, wherein the additional antineoplastic therapy is selected from one or more of surgery, radiotherapy and an antineoplastic agent.

20. The use as claimed in claim 19, wherein the additional antineoplastic therapy is an antineoplastic agent.

21. The use as claimed in claim 20, wherein the additional antineoplastic agent is selected from MEK inhibitors, BRAF inhibitors, EGFR inhibitors, HER2 and / or HER3 inhibitors, Axl inhibitors, PI3K inhibitors, SOS1 inhibitors, signal transduction pathway inhibitors, checkpoint inhibitors, apoptotic pathway modulators, cytotoxic chemotherapeutic agents, angiogenesis-directed therapies, and immune system-directed agents.

22. The use as claimed in claim 21, wherein the additional antineoplastic agent is a MEK inhibitor. 293 23. The use as claimed in claim 22, wherein the MEK inhibitor is binimetinib, or a pharmaceutically acceptable salt thereof.

24. The use as claimed in claim 21, wherein the additional antineoplastic agent is an EGFR inhibitor.

25. The use as claimed in claim 24, wherein the EGFR inhibitor is cetuximab.

26. A compound according to any of claims 1 or 2 or a pharmaceutically acceptable salt thereof for use in the treatment of a BRAF-associated tumor in a subject in need.

27. The pharmaceutically acceptable compound or salt thereof for use in accordance with claim 26, wherein said BRAF-associated tumor has a BRAF class II mutation.

28. The pharmaceutically acceptable compound or salt thereof for use in accordance with claim 27, wherein said BRAF class II mutation is a non-V600 BRAF mutation.

29. The pharmaceutically acceptable compound or salt thereof for use in accordance with claim 28, wherein said non-V600 BRAF mutation is G469A or G469R of BRAF.

30. The pharmaceutically acceptable compound or salt thereof for use in accordance with claim 27, wherein said BRAF class II mutation is a BRAF V600E splice variant.

31. The pharmaceutically acceptable compound or salt thereof for use in accordance with claim 30, wherein said BRAF V600E splice variant is p61BRAF(V600E).

32. The pharmaceutically acceptable compound or salt thereof for use in accordance with any of claims 26 to 31, wherein said BRAF-associated tumor is a cancer type selected from lung cancer, melanoma, colorectal cancer, breast cancer, pancreatic cancer, thyroid cancer, prostate cancer, adenoid cystic carcinoma, appendiceal cancer, small bowel cancer, squamous cell carcinoma of the head and neck, angiosarcoma, bladder carcinoma, plasma cell neoplasia, hepatopancreatobiliary carcinoma, ovarian carcinoma, neuroendocrine cancer, cholangiocarcinoma, and CNS cancer types.

33. The pharmaceutically acceptable compound or salt thereof for use in accordance with any of claims 26 to 32, wherein said cancer is a type of metastatic cancer. 294 34. The pharmaceutically acceptable compound or salt thereof for use in accordance with claim 33, wherein said cancer is a type of metastatic CNS cancer.

35. The pharmaceutically acceptable compound or salt thereof for use in accordance with any of claims 26 to 31, wherein said BRAF-associated tumor is a primary brain tumor.

36. The pharmaceutically acceptable compound or salt thereof for use in accordance with claim 35, wherein said primary brain tumor is a grade 2 glioma, grade 3 glioma, or grade 4 glioma.

37. The pharmaceutically acceptable compound or salt thereof for use in accordance with claim 26, wherein said BRAF-associated tumor has a BRAF class I mutation.

38. The pharmaceutically acceptable compound or salt thereof for use in accordance with claim 37, wherein said BRAF class I mutation is BRAF V600E or BRAF V600K.

39. The pharmaceutically acceptable compound or salt thereof for use in accordance with claim 37 or 38, wherein said BRAF-associated tumor is selected from melanoma, colorectal cancer, thyroid cancer, non-small cell lung cancer, ovarian cancer, renal cell carcinoma and metastatic cancer types thereof and primary brain tumors.

40. The pharmaceutically acceptable compound or salt thereof for use in accordance with any of claims 26 to 39, wherein the pharmaceutically acceptable compound or salt thereof is adapted to be further administered with additional antineoplastic therapy.

41. The pharmaceutically acceptable compound or salt thereof for use in accordance with claim 40, wherein the additional antineoplastic therapy is selected from one or more of surgery, radiotherapy and an antineoplastic agent.

42. The pharmaceutically acceptable compound or salt thereof for use in accordance with claim 41, wherein the additional antineoplastic therapy is an antineoplastic agent.

43. The pharmaceutically acceptable compound or salt thereof for use in accordance with claim 42, wherein the additional antineoplastic agent is selected from MEK inhibitors, BRAF inhibitors, EGFR inhibitors, HER2 and / or HER3 inhibitors, Axl inhibitors, PI3K inhibitors, SOS1 inhibitors, signal transduction pathway inhibitors, checkpoint inhibitors, apoptotic pathway modulators, cytotoxic chemotherapeutic agents, angiogenesis-directed therapies, and immune system-directed agents.

44. The pharmaceutically acceptable compound or salt thereof for use in accordance with claim 43, wherein the additional antineoplastic agent is a MEK inhibitor 5.

45. The pharmaceutically acceptable compound or salt thereof for use in accordance with claim 44, wherein the MEK inhibitor is binimetinib, or a pharmaceutically acceptable salt thereof.

46. ​​The pharmaceutically acceptable compound or salt thereof for use 10 in accordance with claim 43, wherein the additional antineoplastic agent is an EGFR inhibitor.

47. The pharmaceutically acceptable compound or salt thereof for use in accordance with claim 46, wherein the EGFR inhibitor is cetuximab.