BCR-ABL1 inhibitors for use in treating cancer

Abstract

The present disclosure is directed to methods of treating cancer in a subject in need thereof with Compound (1): or a pharmaceutically acceptable salt thereof, or a tautomer of Compound (1) or a pharmaceutically acceptable salt thereof, or a prodrug thereof, or a pharmaceutical composition comprising any of the foregoing. Methods for dosing Compound (1) are also provided by the present disclosure.

Description

[0001]Attorney Docket No.: TRPH-054 / 001WO 346923-2814 BCR-ABL1 INHIBITORS FOR USE IN TREATING CANCER CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to and the benefit of U.S. Provisional Application Nos.63 / 637,869, filed on April 23, 2024, and 63 / 762,602, filed on February 24, 2025, each of which are incorporated by reference herein in their entirety for all purposes. FIELD OF THE INVENTION Provided herein are compounds, preferably compounds inhibiting tyrosine kinase enzymatic activity of a protein selected from Abelson protein (ABL1), Abelson-related protein (ABL2), or a chimeric protein BCR-ABL1, compositions thereof, and methods of their preparation, and methods of inhibiting tyrosine kinase enzymatic activity of a protein selected from Abelson protein (ABL1), Abelson-related protein (ABL2), or a chimeric protein BCR-ABL1, and methods for treating diseases wherein modulation of BCR-ABL1 activity prevents, inhibits, or ameliorates the pathology and / or symptomology of the disease. BACKGROUND In chronic myeloid leukemia (CML) the Philadelphia chromosome (Ph), formed by the t(9,22) reciprocal chromosome, translocates in a haematopoietic stem cell. This chromosome carries the BCR-ABL1 oncogene which encodes the chimeric BCR-ABL1 protein. CML is a cancer that occurs when the blood-forming cells of the bone marrow overproduce white blood cells. In the United States, CML is an orphan indication with approximately 8,930 new cases expected to be diagnosed in 2023. Drugs that inhibit the tyrosine kinase activity of BCR-ABL1 via an ATP competitive mechanism, such as Gleevec® / Glivec® (imatinib), Tasigna® (nilotinib) and Sprycel® (dasatinib), may be effective in treating CML; however, some patients relapse due to the emergence of drug- resistant clones. Despite improvements in outcomes with active-site targeting TKIs, many patients do not achieve long-term disease control with these therapies due to resistance or intolerance, leading patients to cycle through prior generation treatments. As a result, physicians and patients are seeking additional efficacious therapies for people whose tolerability, co-morbidity and / or drug-drug interaction profiles change over time, limiting their available treatment options, quality of life and the effectiveness of mainstay therapies. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 Allosteric BCR-ABL TKIs are the only class of drug to show efficacy and tolerability benefits compared with active-site TKIs, and represent an important advancement in the treatment of CML. Compound 1 is an oral, potent, and novel allosteric BCR-ABL inhibitor specifically targeting the BCR-ABL myristoyl pocket, which is in clinical development for chronic myeloid leukemia. Asciminib is the only currently approved allosteric BCR-ABL inhibitor. Compound 1 was designed to be a differentiated BCR-ABL inhibitor that could have efficacy, safety and tolerability equal to or greater than asciminib with more convenient dosing and minimal drug interactions to improve outcomes and quality of life for people living with CML as a chronic disease. Asciminib, the only currently approved allosteric BCR-ABL inhibitor, requires three hours of fasting with each dose, twice-daily dosing in multiple clinical settings and dose modifications and avoidance of many co-administered medications due to CYP-mediated drug interactions. Accordingly, clinically efficacious treatments using compounds that inhibit the activity of BCR-ABL1 and BCR-ABL1 mutations via the ATP binding site, the myristoyl binding site or a combination of both sites are lacking, and the present disclosure aims to satisfy this presently unmet clinical need. SUMMARY In some embodiments, the present disclosure is directed to a method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, known as (R)-N-(4- (chlorodifluoromethoxy)phenyl)-2-(difluoromethyl)-1-(1-hydroxypropan-2-yl)-7-(pyrimidin- 5-yl)-1H-benzo[d]imidazole-5-carboxamide): (Compound 1), or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered at a daily dosage of between about 5 mg 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 and about 700 mg, and wherein the difference between AUCinf of Compound 1 if administered under fed conditions and AUCinf of Compound 1 if administered under fasted conditions is less than about 40%. In some embodiments, the present disclosure is directed to a method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered at a daily dosage of between about 5 mg and about 700 mg, and wherein the difference between Cmaxof Compound 1 if administered under fed conditions and Cmaxof Compound 1 if administered under fasted conditions is less than about 60%. In some embodiments, the present disclosure is directed to a method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof by administering Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 to the subject, wherein the cancer is a leukemia. In some embodiments, the present disclosure is directed to a method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, wherein Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered with food. In some embodiments, the present disclosure is directed to a method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, wherein Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered without food. In some embodiments, the present disclosure is directed to a kit comprising Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, and printed instructions for using Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 in a subject for the treatment for leukemia. In some embodiments, the present disclosure is directed to a method of inhibiting tyrosine kinase enzymatic activity of a protein selected from the group consisting of Abelson protein (ABL1), Abelson-related protein (ABL2), and a chimeric protein BCR-ABL1, comprising administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered at a daily dosage of between about 5 mg and about 700 mg, and wherein the 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 difference between AUCinf of Compound 1 if administered under fed conditions and AUCinf of Compound 1 if administered under fasted conditions is less than about 40%. In some embodiments, the present disclosure is directed to a method of inhibiting tyrosine kinase enzymatic activity of a protein selected from the group consisting of Abelson protein (ABL1), Abelson-related protein (ABL2), and a chimeric protein BCR-ABL1, comprising administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered at a daily dosage of between about 5 mg and about 700 mg, and wherein the difference between Cmaxof Compound 1 if administered under fed conditions and Cmaxof Compound 1 if administered under fasted conditions is less than about 60%. In some embodiments, the present disclosure is directed to a method of treating a disease, wherein modulation of BCR-ABL1 activity prevents, inhibits, or ameliorates the pathology and / or symptomology of the disease, in a patient, comprising administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered at a daily dosage of between about 5 mg and about 700 mg, and wherein the difference between AUCinf of Compound 1 if administered under fed conditions and AUCinf of Compound 1 if administered under fasted conditions is less than about 40%. In some embodiments, the present disclosure is directed to a method of treating a disease, wherein modulation of BCR-ABL1 activity prevents, inhibits, or ameliorates the pathology and / or symptomology of the disease, in a patient, comprising administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered at a daily dosage of between about 5 mg and about 700 mg, and wherein the difference between Cmaxof Compound 1 if administered under fed conditions and Cmaxof Compound 1 if administered under fasted conditions is less than about 60%. In some embodiments, the present disclosure is directed to a method of treating leukemia in a patient comprising administering to the patient a therapeutically effective amount of Compound 1, or a pharmaceutically acceptable salt thereof, wherein the leukemia is chronic myeloid leukemia (CML), acute myeloid leukemia (AML), or acute lymphoblastic leukemia (ALL). In some embodiments, Compound 1 is prepared as provided in U.S. Patent No. 10,889,571, the contents of which are incorporated by reference. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, the present disclosure provides a method of treating a cancer, the method comprising administering Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, to a subject in need thereof at a dosage disclosed herein. In some embodiments, the present disclosure provides a method of treating a cancer, the method comprising administering a composition comprising Compound 1, or the pharmaceutically acceptable salt thereof, to a subject in need thereof at a dosage disclosed herein. In some embodiments, the present disclosure provides a composition comprising Compound 1, or the pharmaceutically acceptable salt thereof for use in treating a cancer in a subject in need thereof at a dosage disclosed herein. In some embodiments, the present disclosure provides Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 for use in treating a cancer in a subject in need thereof at a dosage disclosed herein. In some embodiments, the present disclosure provides Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 for use in treating leukemia in a subject in need thereof at a dosage disclosed herein. In some embodiments, described herein is use of a composition (e.g., a composition comprising Compound 1, or the pharmaceutically acceptable salt thereof) in the manufacture of a medicament for the treatment of a cancer in a subject in need thereof at a dosage disclosed herein. In some embodiments, described herein is use of Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 in the manufacture of a medicament for the treatment of a cancer in a subject in need thereof at a dosage disclosed herein. In some embodiments, described herein is use of Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 in the manufacture of a medicament for the treatment of leukemia in a subject in need thereof at a dosage disclosed herein. In some embodiments, provided herein is a method of inhibiting tyrosine kinase enzymatic activity of a protein selected from the group consisting of Abelson protein (ABL1), Abelson-related protein (ABL2), and a chimeric protein BCR-ABL1, comprising 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 contacting an effective amount of Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, to the protein. In some embodiments, provided herein is a method of treating a disease, wherein modulation of BCR-ABL1 activity prevents, inhibits, or ameliorates the pathology and / or symptomology of the disease, in a patient, comprising administering to the patient a therapeutically effective amount of Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1. In some embodiments, provided herein is a method of treating leukemia in a patient comprising administering to the patient a therapeutically effective amount of Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein the leukemia is chronic myeloid leukemia (CML), acute myeloid leukemia (AML), or acute lymphoblastic leukemia (ALL). BRIEF DESCRIPTION OF THE DRAWINGS The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee. The accompanying drawings, which are incorporated into and form a part of the specification, illustrate several embodiments of the present disclosure and, together with the description, serve to explain the principles of the present disclosure. The drawings are only for the purpose of illustrating an embodiment of the disclosure and are not to be construed as limiting the invention. Further objects, features and advantages of the invention will become apparent from the following detailed description taken in conjunction with the accompanying figures showing illustrative embodiments of the disclosure. FIG.1A depicts the PK profiles following administration, at fasted conditions, of single doses of 20 mg, 40 mg, 80 mg, and 160 mg up to 24 hours postdose. Below limit of quantification (BLQ) values after first measurable concentration are reported as ½*(lower limit of quantification, LLOQ) in the figure. LLOQ is 1 ng / mL. IC90 values shown in figure are as follows: KCL22-s (most sensitive non-T315I cell lines) total IC90 = 15.3 ng / mL; KCL22-r (least sensitive non-T315I cell lines) total IC90 = 72.2 ng / mL. FIG.1B depicts the PK profiles following administration, at fasted and fed conditions, of a single dose of 80 mg up to 24 hours postdose. Below limit of quantification (BLQ) values after first measurable concentration are reported as ½*LLOQ in the figure. LLOQ is 1 ng / mL. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 FIG.2 depicts the PK profiles following administration, at fasted conditions, of single doses of Compound 1 at 20 mg, 40 mg, 80 mg, 160 mg, 320 mg, and 400 mg up to 24 hours postdose. DETAILED DESCRIPTION It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination. This disclosure also includes all salts, such as pharmaceutically acceptable salts, of Compound 1 referred to herein. All forms of Compound 1 are also embraced by the invention, such as crystalline or non-crystalline forms of Compound 1. Compositions comprising Compound 1 are also intended, such as a composition of substantially pure Compound 1. Definitions As used herein, the following definitions shall apply unless otherwise indicated. Further, if any term or symbol used herein is not defined as set forth below, it shall have its ordinary meaning in the art. As used herein, the term “comprising” is intended to mean that the compositions and methods include the recited elements, but not excluding others. “Consisting essentially of” when used to define compositions and methods, shall mean excluding other elements of any essential significance to the combination. For example, a composition consisting essentially of the elements as defined herein would not exclude other elements that do not materially affect the basic and novel characteristic(s) of the claimed invention. “Consisting of” shall mean excluding more than trace amount of, e.g., other ingredients and substantial method steps recited. Embodiments defined by each of these transition terms are within the scope of this invention. In the claims, as well as in the specification above, all transitional phrases such as “comprising,” “including,” “carrying,” “having,” “containing,” “involving,” “holding,” “composed of,” and the like are to be understood to be open-ended, i.e., to mean including but not limited to. Only the transitional phrases “consisting of” and “consisting essentially of” shall be closed or semi-closed transitional phrases, respectively, as set forth in the United States Patent Office Manual of Patent Examining Procedures, Section 2111.03. 7 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 As used herein, the term “therapeutically effective amount”, refers to an amount of a pharmaceutical agent to treat, ameliorate, or prevent an identified disease or condition, or to exhibit a detectable therapeutic or inhibitory effect. The effect can be detected by any assay method known in the art. The precise effective amount for a subject will depend upon the subject’s body weight, size, and health; the nature and extent of the condition; and the therapeutic or combination of therapeutics selected for administration. Therapeutically effective amounts for a given situation can be determined by routine experimentation that is within the skill and judgment of the clinician. As used herein, the term “patient” refers to mammals and includes humans and non- human mammals. Examples of patients include, but are not limited to mice, rats, hamsters, guinea pigs, pigs, rabbits, cats, dogs, goats, sheep, cows, and humans. In some embodiments, patient refers to a human. As used herein, the term “subject in need thereof” refers to a subject having a disease or having an increased risk of developing the disease. A subject in need thereof can be one who has been previously diagnosed or identified as having a disease or disorder disclosed herein. A subject in need thereof can also be one who is suffering from a disease or disorder disclosed herein. Alternatively, a subject in need thereof can be one who has an increased risk of developing such disease or disorder relative to the population at large (i.e., a subject who is predisposed to developing such disorder relative to the population at large). A subject in need thereof can have a refractory or resistant a disease or disorder disclosed herein (i.e., a disease or disorder disclosed herein that does not respond or has not yet responded to treatment). The subject may be resistant at start of treatment or may become resistant during treatment. In some embodiments, the subject in need thereof received and failed all known effective therapies for a disease or disorder disclosed herein. As used herein, the term “pharmaceutically acceptable” refers to safe and non-toxic, preferably for in vivo, more preferably, for human administration. As used herein, the term “pharmaceutically acceptable salt” refers to a pharmaceutical salt that is, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, and allergic response, and is commensurate with a reasonable benefit / risk ratio. Pharmaceutically-acceptable salts are well known in the art. For example, S. M. Berge et al. describes pharmacologically acceptable salts in J. Pharm. Sci., 1977, 66, 1–19. Included in the present teachings are pharmaceutically acceptable salts of Compound 1. Compounds having basic groups can form pharmaceutically acceptable salts with 8 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 pharmaceutically acceptable acid(s). Suitable pharmaceutically acceptable acid addition salts of compounds include salts of inorganic acids (such as hydrochloric acid, hydrobromic, phosphoric, metaphosphoric, nitric, and sulfuric acids) and of organic acids (such as acetic acid, benzenesulfonic, benzoic, ethanesulfonic, methanesulfonic, succinic, and trifluoroacetic acid acids). Compounds with acidic groups such as carboxylic acids can form pharmaceutically acceptable salts with pharmaceutically acceptable base(s). Suitable pharmaceutically acceptable basic salts include ammonium salts, alkali metal salts (such as sodium and potassium salts) and alkaline earth metal salts (such as magnesium and calcium salts). As used herein, the term “pharmaceutically acceptable excipient” means an excipient that is useful in preparing a pharmaceutical composition that is generally safe, non-toxic and neither biologically nor otherwise undesirable, and includes excipient that is acceptable for veterinary use as well as human pharmaceutical use. A “pharmaceutically acceptable excipient” as used in the specification and claims includes both one and more than one such excipient. As used herein, the term “pharmaceutical composition” is a formulation containing Compound 1 of the present disclosure in a form suitable for administration to a subject. In one embodiment, the pharmaceutical composition is in bulk or in unit dosage form. The unit dosage form is any of a variety of forms, including, for example, a capsule, an IV bag, a tablet, a single pump on an aerosol inhaler or a vial. The quantity of active ingredient (e.g., a formulation of the disclosed compound or salt, hydrate, solvate or isomer thereof) in a unit dose of composition is an effective amount and is varied according to the particular treatment involved. One skilled in the art will appreciate that it is sometimes necessary to make routine variations to the dosage depending on the age and condition of the patient. The dosage will also depend on the route of administration. A variety of routes are contemplated, including oral, pulmonary, rectal, parenteral, transdermal, subcutaneous, intravenous, intramuscular, intraperitoneal, inhalational, buccal, sublingual, intrapleural, intrathecal, intranasal, and the like. Dosage forms for the topical or transdermal administration of Compound 1 include powders, sprays, ointments, pastes, creams, lotions, gels, solutions, patches and inhalants. In one embodiment, the active compound is mixed under sterile conditions with a pharmaceutically acceptable carrier, and with any preservatives, buffers, or propellants that are required. It is to be understood that a compound or pharmaceutical composition of the disclosure can be administered to a subject in many of the well-known methods currently 9 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 used for chemotherapeutic treatment. For example, a compound of the disclosure may be injected into the blood stream or body cavities or taken orally or applied through the skin with patches. The dose chosen should be sufficient to constitute effective treatment but not so high as to cause unacceptable side effects. The state of the disease condition (e.g., a disease or disorder disclosed herein) and the health of the patient should preferably be closely monitored during and for a reasonable period after treatment. Dosage and administration are adjusted to provide sufficient levels of the active agent(s) or to maintain the desired effect. Factors which may be taken into account include the severity of the disease state, general health of the subject, age, weight, and gender of the subject, diet, time and frequency of administration, drug combination(s), reaction sensitivities, and tolerance / response to therapy. As used herein, the term “prodrug” refers to a compound that, after administration, is metabolized or otherwise converted to a biologically active or more active compound (or drug) with respect to at least one property. A prodrug, relative to the drug, is modified chemically in a manner that renders it, relative to the drug, less active or inactive, but the chemical modification is such that the corresponding drug is generated by metabolic or other biological processes after the prodrug is administered. A prodrug may have, relative to the active drug, altered metabolic stability or transport characteristics, fewer side effects or lower toxicity, or improved flavor (for example, see the reference Nogrady, 1985, Medicinal Chemistry A Biochemical Approach, Oxford University Press, New York, pages 388-392, incorporated herein by reference). A prodrug may be synthesized using reactants other than employing the corresponding drug. For illustration and without limitation, prodrugs include, carboxy esters, linear and cyclic phosphate esters and phosphoramide and phosphoramidates, carbamates, preferably phenolic carbamates (i.e., carbamates where the hydroxy group is part of an aryl or heteroaryl moiety, where the aryl and heteroaryl may be optionally substituted), and the likes. As used herein, the term “salt” refers to an ionic compound formed between an acid and a base. As used herein, the term “treating” or “treatment” of a disease in a patient refers to 1) preventing the disease from occurring in a patient that is predisposed or does not yet display symptoms of the disease; 2) inhibiting the disease or arresting its development; or 3) ameliorating or causing regression of the disease. As used herein, “treatment” or “treating” is an approach for obtaining beneficial or desired results including clinical results. For purposes of this disclosure, beneficial or desired results include, but are not limited to, one or more of 10 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 the following: decreasing one more symptoms resulting from the disease or disorder, diminishing the extent of the disease or disorder, stabilizing the disease or disorder (e.g., preventing or delaying the worsening of the disease or disorder), delaying the occurrence or recurrence of the disease or disorder, delay or slowing the progression of the disease or disorder, ameliorating the disease or disorder state, providing a remission (whether partial or total) of the disease or disorder, decreasing the dose of one or more other medications required to treat the disease or disorder, enhancing the effect of another medication used to treat the disease or disorder, delaying the progression of the disease or disorder, increasing the quality of life, and / or prolonging survival of a patient. Also encompassed by “treatment” is a reduction of pathological consequence of the disease or disorder. The methods of the invention contemplate any one or more of these aspects of treatment. As used herein, the term “preventing,” “prevent,” or “protecting against” describes reducing or eliminating the onset of the symptoms or complications of such disease, condition or disorder. The term “fed conditions” refers to the consumption or uptake of calories , in either solid or liquid forms, or calories, in any suitable form, before or at the same time when Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered. For example, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 may be administered to the subject (e.g., a human) within minutes or hours of consuming calories (e.g., a meal). In some embodiments, the active ingredients may be administered to the subject (e.g., a human) within 5-10 minutes, about 30 minutes, about 60 The term “fasted conditions” refers to a subject (e.g., a human) fasting at least about 1 hour before or after being administered Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1. As used herein, the term “optional” or “optionally” as used throughout the specification means that the subsequently described event or circumstance may but need not occur, and that the description includes instances where the event or circumstance occurs and instances in which it does not. As used herein, the term “stereoisomer” or “stereoisomers” refer to compounds that differ in the stereogenicity of the constituent atoms such as, without limitation, in the chirality of one or more stereocenters or related to the cis or trans configuration of a carbon-carbon or carbon-nitrogen double bond. Stereoisomers include enantiomers and diastereomers. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 This disclosure also includes all salts, such as pharmaceutically acceptable salts, of Compound 1. This disclosure also includes any or all of the stereochemical forms, including any enantiomeric or diastereomeric forms, and any tautomers or other forms, such as solvates, prodrugs, or isotopomers, of Compound 1. Unless stereochemistry is explicitly indicated in a chemical structure or name, the structure or name is intended to embrace all possible stereoisomers of a compound depicted. In addition, where a specific stereochemical form is depicted, it is understood that other stereochemical forms are also embraced by the invention. All forms of Compound 1 are also embraced by the invention, such as crystalline or non-crystalline forms of Compound 1. Compositions comprising Compound 1 of the invention are also intended, such as a composition of substantially pure Compound 1, including a specific stereochemical form thereof. Compositions comprising a mixture of two or more stereochemical forms of Compound 1 in any ratio are also embraced by the invention, such that racemic, non-racemic, enantioenriched and scalemic mixtures of Compound 1 are embraced. Unless explicitly indicated otherwise, the terms “approximately” and “about” are synonymous. In one embodiment, “approximately” and “about” refer to the recited amount, value, or duration ± 5%, ± 4.5%, ± 4%, ±3.5%, ±3%, ±2.5%, ±2%, ±1.75%, ±1.5%, ±1.25%, ±1%, ±0.9%, ±0.8%, ±0.7%, ±0.6%, ± 0.5% ±0.4%, ±0.3%, ±0.2%, ±0.1%, ±0.09%, ±0.08%, ±0.07%, ±0.06%, ±0.05%, ±0.04%, ±0.03%, ±0.02%, or ±0.01%. In another embodiment, “approximately” and “about” refer to the listed amount, value, or duration ±2.5%, ±2%, ±1.75%, ±1.5%, ±1.25%, ±1%, ±0.9%, ±0.8%, ±0.7%, ±0.6%, ± 0.5%. In yet another embodiment, “approximately” and “about” refer to the listed amount, value, or duration ±1%. In yet another embodiment, “approximately” and “about” refer to the listed amount, value, or duration ±0.5%. In yet another embodiment, “approximately” and “about” refer to the listed amount, value, or duration ±0.1%. As used herein, the phrase “and / or,” as used herein in the specification and in the claims, should be understood to mean “either or both” of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases. Multiple elements listed with “and / or” should be construed in the same fashion, i.e., “one or more” of the elements so conjoined. Other elements may optionally be present other than the elements specifically identified by the “and / or” clause, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, a reference to “A and / or B”, when used in conjunction with open-ended language such as “comprising” can refer, in one embodiment, to A only (optionally including elements other than B); in another 12 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 embodiment, to B only (optionally including elements other than A); in yet another embodiment, to both A and B (optionally including other elements); etc. As used herein in the specification and in the claims, the phrase “at least one,” in reference to a list of one or more elements, should be understood to mean at least one element selected from anyone or more of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements. This definition also allows that elements may optionally be present other than the elements specifically identified within the list of elements to which the phrase “at least one” refers, whether related or unrelated to those elements specifically identified. Thus, as a nonlimiting example, “at least one of A and B” (or, equivalently, “at least one of A or B,” or, equivalently “at least one of A and / or B”) can refer, in one embodiment, to at least one, optionally including more than one, A, with no B present (and optionally including elements other than B); in another embodiment, to at least one, optionally including more than one, B, with no A present (and optionally including elements other than A); in yet another embodiment, to at least one, optionally including more than one, A, and at least one, optionally including more than one, B (and optionally including other elements); etc. Abbreviations 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 All publications and patent documents cited herein are incorporated herein by reference as if each such publication or document was specifically and individually indicated to be incorporated herein by reference. Citation of publications and patent documents is not intended as an admission that any is pertinent prior art, nor does it constitute any admission as to the contents or date of the same. The invention having now been described by way of written description, those of skill in the art will recognize that the invention can be practiced in a variety of embodiments and that the foregoing description and examples below are for purposes of illustration and not limitation of the claims that follow. Other features and advantages of the present disclosure are apparent from the different examples. The provided examples illustrate different components and methodology useful in practicing the present disclosure. The examples do not limit the claimed disclosure. Based on the present disclosure the skilled artisan can identify and employ other components and methodology useful for practicing the present disclosure. Pharmaceutical Compositions and Formulations Pharmaceutical compositions of Compound 1 (Compound 1), or a pharmaceutically acceptable salt thereof are embraced by this invention. Thus, the invention includes pharmaceutical compositions comprising Compound 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, diluent, or excipient. In some embodiments, the pharmaceutically acceptable salt is an acid addition salt, such as a salt formed with an inorganic or organic acid. Pharmaceutical compositions according to the invention may take a form suitable for oral, buccal, parenteral, nasal, topical or rectal administration or a form suitable for administration by inhalation. “Pharmaceutically acceptable carrier” and “pharmaceutically acceptable diluent” refer to a substance that aids the formulation and / or administration of an active agent to and / or 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 absorption by a subject and can be included in the compositions of the present disclosure without causing a significant adverse toxicological effect on the subject. Non-limiting examples of pharmaceutically acceptable carriers and / or diluents include water, NaCl, normal saline solutions, lactated Ringer’s, normal sucrose, normal glucose, binders, fillers, disintegrants, lubricants, coatings, sweeteners, flavors, salt solutions (such as Ringer’s solution), alcohols, oils, gelatins, carbohydrates such as lactose, amylose or starch, fatty acid esters, hydroxymethycellulose, polyvinyl pyrrolidine, and colors, and the like. Such preparations can be sterilized and, if desired, mixed with auxiliary agents such as lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, coloring, and / or aromatic substances and the like that do not deleteriously react with or interfere with the activity of Compound 1 provided herein. One of ordinary skill in the art will recognize that other pharmaceutical excipients are suitable for use with disclosed Compound 1. The pharmaceutical compositions of the present teachings optionally include one or more pharmaceutically acceptable carriers and / or diluents therefor, such as lactose, starch, cellulose and dextrose. Other excipients, such as flavoring agents; sweeteners; and preservatives, such as methyl, ethyl, propyl and butyl parabens, can also be included. More complete listings of suitable excipients can be found in the Handbook of Pharmaceutical Excipients (5thEd., Pharmaceutical Press (2005)). A person skilled in the art would know how to prepare formulations suitable for various types of administration routes. Conventional procedures and ingredients for the selection and preparation of suitable formulations are described, for example, in Remington’s Pharmaceutical Sciences (2003 - 20th edition) and in The United States Pharmacopeia: The National Formulary (USP 24 NF19) published in 1999. The carriers, diluents and / or excipients are “acceptable” in the sense of being compatible with the other ingredients of the pharmaceutical composition and not deleterious to the recipient thereof. The term “dosage holiday”, also referred to as “drug holiday,” refers to a period of time wherein the subject is not administered or administered at a lower dosage of the therapeutic (i.e., Compound 1). The timing of a dosage holiday depends on the timing of the regular dosing regimen and the purpose for taking the dosage holiday (e.g., to regain drug sensitivity and / or to reduce unwanted side effects of continuous, long- term administration). In some embodiments, the dosage holiday may be a reduction in the dosage of the drug (e.g., to below the therapeutically effective amount for a certain interval of time). In other embodiments, administration of the dosage is stopped for a certain interval of time before 15 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 administration is started again at the same or different dosing regimen (e.g., at a lower or higher dose and / or frequency of administration). A dosage holiday of the disclosure may thus be selected from a wide range of time-periods and dosage regimens. In some embodiments, Compound 1 may be in a purified form and compositions comprising Compound 1 in purified forms are detailed herein. Compositions comprising Compound 1 or a salt thereof are provided, such as compositions of substantially pure Compound 1. In some embodiments, a composition containing Compound 1 or a salt thereof is in substantially pure form. In one variation, “substantially pure” intends a composition that contains no more than 35% impurity, wherein the impurity denotes a compound other than Compound 1 comprising the majority of the composition or a salt thereof. For example, a composition of a substantially pure Compound 1 intends a composition that contains no more than 35% impurity, wherein the impurity denotes a compound other than Compound 1 or a salt thereof. In one variation, a composition of substantially pure Compound 1 or a salt thereof is provided wherein the composition contains no more than 25% impurity. In another variation, a composition of substantially pure Compound 1 or a salt thereof is provided wherein the composition contains or no more than 20% impurity. In still another variation, a composition of substantially pure Compound 1 or a salt thereof is provided wherein the composition contains or no more than 10% impurity. In a further variation, a composition of substantially pure Compound 1 or a salt thereof is provided wherein the composition contains or no more than 5% impurity. In another variation, a composition of substantially pure Compound 1 or a salt thereof is provided wherein the composition contains or no more than 3% impurity. In still another variation, a composition of substantially pure Compound 1 or a salt thereof is provided wherein the composition contains or no more than 1% impurity. In a further variation, a composition of substantially pure Compound 1 or a salt thereof is provided wherein the composition contains or no more than 0.5% impurity. In yet other variations, a composition of substantially pure compound means that the composition contains no more than 15% or preferably no more than 10% or more preferably no more than 5% or even more preferably no more than 3% and most preferably no more than 1% impurity, which impurity may be Compound 1 in a different stereochemical form. For instance, and without limitation, a composition of substantially pure (R) compound means that the composition contains no more than 15% or no more than 10% or no more than 5% or no more than 3% or no more than 1% of the (S) form of the compound. In one variation, Compound 1 herein is prepared for administration to an individual such as a human. In another variation, compositions are provided containing Compound 1 in 16 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 substantially pure form. In another variation, the invention embraces pharmaceutical compositions comprising Compound 1 and a pharmaceutically acceptable carrier or excipient. In another variation, methods of administering Compound 1 are provided. The purified forms, pharmaceutical compositions and methods of Compound 1 are suitable for any form of Compound 1. Compound 1 may be formulated for any available delivery route, including an oral, mucosal (e.g., nasal, sublingual, vaginal, buccal or rectal), parenteral (e.g., intramuscular, subcutaneous or intravenous), topical or transdermal delivery form. Compound 1 may be formulated with suitable carriers to provide delivery forms that include, but are not limited to, tablets, caplets, capsules (such as hard gelatin capsules or soft elastic gelatin capsules), cachets, troches, lozenges, gums, dispersions, suppositories, ointments, cataplasms (poultices), pastes, powders, dressings, creams, solutions, patches, aerosols (e.g., nasal spray or inhalers), gels, suspensions (e.g., aqueous or non-aqueous liquid suspensions, oil-in-water emulsions or water-in-oil liquid emulsions), solutions and elixirs. Compound 1 can be used in the preparation of a formulation, such as a pharmaceutical formulation, by combining Compound 1 as an active ingredient with a pharmaceutically acceptable carrier, such as those mentioned above. Depending on the therapeutic form of the system (e.g., transdermal patch vs. oral tablet), the carrier may be in various forms. In addition, pharmaceutical formulations may contain preservatives, solubilizers, stabilizers, re-wetting agents, emulgators, sweeteners, dyes, adjusters, and salts for the adjustment of osmotic pressure, buffers, coating agents or antioxidants. Formulations comprising Compound 1 may also contain other substances which have valuable therapeutic properties. Pharmaceutical formulations may be prepared by known pharmaceutical methods. Suitable formulations can be found, e.g., in Remington: The Science and Practice of Pharmacy, Lippincott Williams & Wilkins, 21sted. (2005), which is incorporated herein by reference. Compound 1 may be administered to individuals (e.g., a human) in a form of generally accepted oral compositions, such as tablets, coated tablets, and gel capsules in a hard or in soft shell, emulsions or suspensions. Examples of carriers, which may be used for the preparation of such compositions, are lactose, corn starch or its derivatives, talc, stearate or its salts, etc. Acceptable carriers for gel capsules with soft shell are, for instance, plant oils, wax, fats, semisolid and liquid polyols, and so on. In addition, pharmaceutical formulations may contain preservatives, solubilizers, stabilizers, re-wetting agents, emulgators, sweeteners, 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 dyes, adjusters, and salts for the adjustment of osmotic pressure, buffers, coating agents or antioxidants. Compound 1 can be formulated in a tablet in any dosage form described. Compositions comprising Compound 1 are also described. In one variation, the composition comprises Compound 1 and a pharmaceutically acceptable carrier or excipient. In another variation, a composition of substantially pure Compound 1 is provided. Methods of Use / Treatments Described herein is a method of treating a cancer by administering to the subject an effective amount of Compound 1, or a pharmaceutically acceptable salt thereof, or the corresponding pharmaceutical composition comprising Compound 1. Compositions detailed herein, such as a pharmaceutical composition containing Compound 1, or a salt thereof, and a pharmaceutically acceptable carrier or excipient, may be used in methods of administration and treatment as provided herein. Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 may also be used in in vitro methods, such as in vitro methods of administering Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 to cells for screening purposes and / or for conducting quality control assays. In some embodiments, provided herein is a method of inhibiting tyrosine kinase enzymatic activity of a protein selected from Abelson protein (ABL1), Abelson-related protein (ABL2), or a chimeric protein BCR-ABL1, comprising contacting an effective amount of Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, to the protein. In one embodiment, provided herein is a method of inhibiting tyrosine kinase enzymatic activity of Abelson protein (ABL1) comprising contacting an effective amount of Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 to ABL1. In another embodiment, provided herein is a method of inhibiting tyrosine kinase enzymatic activity of Abelson-related protein (ABL2) comprising contacting an effective amount of Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 to ABL2. In a further embodiment, provided herein is a method of inhibiting tyrosine kinase enzymatic activity of a chimeric protein BCR-ABL1 comprising contacting an effective amount of Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 to the chimeric protein. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, provided herein is a method of treating a disease in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1. In some embodiments, Compound 1, or salt thereof, or the composition is administered according to a dosage described herein. Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 are believed to be effective for treating a variety of diseases and disorders. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 may be used in a method of treating a disease mediated by ABL1, ABL2, and / or BCR-ABL1. In some embodiments, provided herein is a method of treating a disease, wherein modulation of BCR-ABL1 activity prevents, inhibits, or ameliorates the pathology and / or symptomology of the disease, in a patient, comprising administering to the patient a therapeutically effective amount of Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1. In one embodiment, provided herein is a method of treating a disease, wherein modulation of BCR-ABL1 activity prevents the pathology and / or symptomology of the disease, in a patient, comprising administering to the patient a therapeutically effective amount of Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1. In one embodiment, provided herein is a method of treating a disease, wherein modulation of BCR-ABL1 activity inhibits the pathology and / or symptomology of the disease, in a patient, comprising administering to the patient a therapeutically effective amount of Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1. In one embodiment, provided herein is a method of treating a disease, wherein modulation of BCR-ABL1 activity ameliorates the pathology and / or symptomology of the disease, in a patient, comprising administering to the patient a therapeutically effective amount of Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1. In some embodiments, the disease is leukemia. In some embodiments, the leukemia is chronic myeloid leukemia (CML), acute myeloid leukemia (AML), or acute lymphoblastic leukemia (ALL). In some embodiments, the leukemia is chronic myeloid leukemia (CML). In some embodiments, provided herein is a method of treating leukemia in a patient comprising administering to the patient a therapeutically effective amount of Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 Compound 1. In some embodiments, provided herein is a method of treating leukemia in a patient comprising administering to the patient a therapeutically effective amount of Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein the leukemia is chronic myeloid leukemia (CML), acute myeloid leukemia (AML), or acute lymphoblastic leukemia (ALL). In some embodiments, the leukemia treated herein is CML or ALL, and the method further comprises administering a therapeutically effective amount of a compound selected from imatinib, nilotinib, dasatinib, bosutinib, ponatinib, and bafetinib. In some embodiments, the leukemia is CML or ALL, and the method further comprises administering a therapeutically effective amount of a compound selected from imatinib, nilotinib, dasatinib, bosutinib, ponatinib, and bafetinib. In some embodiments, the leukemia is resistant to treatment. In some embodiments, the leukemia is resistant to treatment with imatinib, nilotinib, dasatinib, bosutinib, ponatinib, and / or bafetinib. In some embodiments, the CML is resistant to standard-of-care treatment such as treatment with one or more of imatinib, nilotinib, and dasatinib. In some embodiments, the leukemia progressed during a prior treatment. In some embodiments the prior treatment comprised administration of imatinib, nilotinib, dasatinib, bosutinib, ponatinib, and / or bafetinib. In some embodiments, the method further comprises administering a therapeutically effective amount of a compound selected from imatinib, nilotinib, dasatinib, bosutinib, ponatinib and bafetinib. In some embodiments, the AML is secondary AML, which develops after myelodysplastic syndromes (MDS) or myeloproliferative neo-plasms (MPN). In some embodiments, provided herein is a method of treating a cancer in a patient comprising administering to the patient a therapeutically effective amount of Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1. In some embodiments, the cancer is melanoma, hereditary leiomyomatosis, renal cell carcinoma (HLRCC), or other solid tumors. In some embodiments, the cancer is B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, multiple myeloma, breast cancer, head and neck cancer, soft tissue sarcoma, ovarian cancer, pancreatic cancer, follicular lymphoma, or mantle cell lymphoma. In some embodiments, the cancer to be treated is a lymphoma. Lymphomas which can be treated by the disclosed methods include Non-Hodgkin’s lymphoma; Burkitt’s lymphoma; 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 small lymphocytic lymphoma; lymphoplasmacytic lymphoma; MALT lymphoma; follicular lymphoma; diffuse large B-cell lymphoma; and T-cell lymphoma. Lymphoma is a malignancy in the lymphatic cells of the immune system (e.g. B cells, T cells, or natural killer (NK) cells). Lymphomas often originate in the lymph nodes and present as solid tumors. They can metastasize to other organs such as the brain, bone, or skin. Extranodal sites are often located in the abdomen. Lymphomas are closely related to the lymphoid leukemia and in some cases a particular form of cancer is categorized as both a lymphoma and a leukemia. Leukemias, which can be treated by the disclosed methods, include acute lymphoblastic leukemia (ALL); Burkitt’s leukemia; B-cell leukemia; B-cell acute lymphoblastic leukemia; chronic lymphocytic leukemia (CLL); acute myelogenous leukemia (AML); chronic myelogenous leukemia (CML); and T-cell acute lymphoblastic leukemia (T- ALL). In some embodiments, the cancer to be treated is B-cell neoplasms, B-cell leukemia, B-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, Burkitt's leukemia, acute myelogenous leukemia and / or T-ALL. The maturation of B cells most typically ceases or substantially decreases when the foreign antigen has been neutralized. Occasionally, however, proliferation of a particular B cell will continue unabated; such proliferation can result in a cancer referred to as "B-cell lymphoma" or a "B- cell leukemia." In some embodiments the cancer to be treated is chronic lymphocytic leukemia (CLL) or chronic myelogenous leukemia (CML). In some embodiments, cancer which can be treated by the disclosed methods include colon cancer, liver cancer, gastric cancer, intestinal cancer, esophageal cancer, breast cancer, ovarian cancer, head and neck cancer, lung cancer, and thyroid cancer. In some embodiments, the cancer is relapsed or refractory. In some embodiments, the subject has progressed on prior therapy. In some embodiments, the subject has previously received treatment for CML. In some embodiments, the subject has previously received a TKI treatment. In some embodiments, the subject has previously received at least one second generation TKI (nilotinib, dasatinib or bosutinib). In some embodiments, the subject is intolerant to prior TKI treatment (including asciminib). In some embodiments, the subject was previously treated with asciminib. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In another aspect is provided a method of delaying the onset and / or development of a disease or disorder that is mediated by BCR-ABL1 activity in a patient (such as a human) who is at risk for developing the disease or disorder. It is appreciated that delayed development may encompass prevention in the event the individual or patient does not develop the disease or disorder. In some embodiments, an individual or patient at risk of developing a disease or disorder that is mediated by BCR-ABL1 activity has one or more risk factors for developing the disease or disorder, such as a family history of an individual or patient having the disease or disorder, or having an underlying genetic condition that is associated with an increased likelihood of developing the disease or disorder. In some embodiments, provided herein is a method of delaying the onset and / or development of leukemia in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 provided herein. In one variation, provided herein is a method of delaying the onset and / or development of CML in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 provided herein. In one variation, provided herein is a method of delaying the onset and / or development of AML in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 provided herein. In one variation, provided herein is a method of delaying the onset and / or development of ALL in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 provided herein. Methods of treating a disease mediated by BCR-ABL1, such as various leukemias and the like, are well known to the skilled artisan and can be adapted to treating such a disease with Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 provided herein. In some embodiments, the patient is a mammal. In some embodiments, the patient is a primate, dog, cat, rabbit, or rodent. In some embodiments, the patient is a primate. In some embodiments, the patient is a human. In some embodiments, the human is at least about or is about any of 18, 21, 30, 50, 60, 65, 70, 75, 80, or 85 years old. In some embodiments, the human is a child. In some embodiments, the human is less than about or about any of 21, 18, 15, 10, 5, 4, 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 3, 2, or 1 years old. In some embodiments, the patient has a genetic condition that is associated with an increased likelihood of developing the disease, such as the leukemia. In some embodiments, the patient has a mutation in the ABL1 and / or ABL2 gene. In some embodiments, the patient is Philadelphia chromosome positive. Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 provided herein may be administered to a patient in accordance with an effective dosing regimen for a desired period of time or duration, such as at least about one month, at least about 2 months, at least about 3 months, at least about 6 months, or at least about 12 months or longer, which in some variations may be for the duration of the patient’s life. In one variation, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered on a daily or intermittent schedule. Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 can be administered to a patient continuously (for example, at least once daily) over a period of time. The dosing frequency can also be less than once daily, e.g., about a once weekly dosing. The dosing frequency can be more than once daily, e.g., twice or three times daily. The dosing frequency can also be intermittent (e.g., once daily dosing for 7 days followed by no doses for 7 days, repeated for any 14 day time period, such as about 2 months, about 4 months, about 6 months or more). Any of the dosing frequencies can employ Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 together with any of the dosages described herein. Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 may be administered to a patient via various routes, including, e.g., intravenous, intramuscular, subcutaneous, oral and transdermal. The dose of Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 administered to a patient may vary with the particular method of administration, and the particular disease. In some embodiments, the amount of Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is a therapeutically effective amount. The effective amount of Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 may in one aspect be a dose of between about 0.01 and about 100 mg / kg. Effective amounts or doses of Compound 1 may be ascertained by routine methods, such as modeling, dose escalation, or clinical trials, taking 23 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 into account routine factors, e.g., the mode or route of administration or drug delivery, the pharmacokinetics of the agent, the severity and course of the disease to be treated, the subject’s health status, condition, and weight. An exemplary dose is in the range of about from about 0.7 mg to 7 g in a day, or about 7 mg to 350 mg in a day, or about 350 mg to 1.75 g in a day, or about 1.75 to 7 g in a day. Also provided herein are uses of Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 described herein, in the manufacture of a medicament. In some embodiments, the manufacture of a medicament is for the treatment of a disease described herein. In some embodiments, the manufacture of a medicament is for the treatment of a disease mediated by ABL1, ABL2, and / or BCR-ABL1. In some embodiments, the present disclosure provides a method of treating a cancer comprising administering to a subject in need thereof Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, at a dosage from about 5 mg to about 700 mg. In some embodiments, the present disclosure provides a method of treating a cancer comprising administering to a subject in need thereof a composition comprising Compound 1, or the pharmaceutically acceptable salt thereof, at a dosage from about 5 mg to about 700 mg. In some embodiments, the present disclosure provides a composition comprising Compound 1, or the pharmaceutically acceptable salt thereof, for use in treating cancer in a subject in need thereof at a dosage from about 5 mg to about 700 mg. In some embodiments, the present disclosure provides Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, for use in treating cancer in a subject in need thereof at a dosage from about 5 mg to about 700 mg. In some embodiments, the present disclosure provides use of a composition comprising Compound 1, or the pharmaceutically acceptable salt thereof, for the treatment of cancer in a subject in need thereof at a dosage from about 5 mg to about 700 mg. In some embodiments, the present disclosure provides use of Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, for the treatment of cancer in a subject in need thereof at a dosage from about 5 mg to about 700 mg. In some embodiments, the present disclosure provides use of a composition comprising Compound 1, or the pharmaceutically acceptable salt thereof, in the manufacture 24 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 of a medicament for the treatment of cancer in a subject in need thereof at a dosage from about 5 mg to about 700 mg. In some embodiments, the present disclosure provides the use of Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, in the manufacture of a medicament for the treatment of cancer in a subject in need thereof at a dosage from about 5 mg to about 700 mg. In some embodiments, the subject is a mammal. In some embodiments, the mammal is human. In some embodiments administering Compound 1 comprises providing a subject with a pharmaceutical composition comprising pharmaceutically acceptable salt thereof. Without being bound to any particular theory, may become Compound 1 in particular biological environments, such as in plasma. Methods of Administration and Dosage Forms The precise amount of compound administered to provide an “effective amount” to the subject will depend on the mode of administration, the type, and severity of the disease, and on the characteristics of the subject, such as general health, age, sex, body weight, and tolerance to drugs. The skilled artisan will be able to determine appropriate dosages depending on these and other factors. When administered in combination with other therapeutic agents, e.g., when administered in combination with an anti-cancer agent, an “effective amount” of any additional therapeutic agent(s) will depend on the type of drug used. Suitable dosages are known for approved therapeutic agents and can be adjusted by the skilled artisan according to the condition of the subject, the type of condition(s) being treated and the amount of a compound of the disclosure being used by following, for example, dosages reported in the literature and recommended in the Physician’s Desk Reference (57th ed., 2003). 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 The term “effective amount” means an amount when administered to the subject which results in beneficial or desired results, including clinical results, e.g., inhibits, suppresses or reduces the symptoms of the condition being treated in the subject as compared to a control. For example, a therapeutically effective amount can be given in unit dosage form (e.g., 0.1 mg to about 50 g per day, alternatively from 1 mg to about 5 grams per day). The terms “administer”, “administering”, “administration”, and the like, as used herein, refer to methods that may be used to enable delivery of compositions to the desired site of biological action. These methods include, but are not limited to, intraarticular (in the joints), intravenous, intramuscular, intratumoral, intradermal, intraperitoneal, subcutaneous, orally, topically, intrathecally, inhalationally, transdermally, rectally, and the like. Administration techniques that can be employed with the agents and methods described herein are found in e.g., Goodman and Gilman, The Pharmacological Basis of Therapeutics, current ed.; Pergamon; and Remington’s, Pharmaceutical Sciences (current edition), Mack Publishing Co., Easton, Pa. The particular mode of administration and the dosage regimen will be selected by the attending clinician, taking into account the particulars of the case (e.g., the subject, the disease, the disease state involved, the particular treatment). Treatment can involve daily or multi-daily or less than daily (such as weekly or monthly etc.) doses over a period of a few days to months, or even years. However, a person of ordinary skill in the art would immediately recognize appropriate and / or equivalent doses looking at dosages of approved compositions for treating cancer using Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 for guidance. Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 taught herein can be administered to a patient in a variety of forms depending on the selected route of administration, as will be understood by those skilled in the art. Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 may be administered, for example, by oral, parenteral, buccal, sublingual, nasal, rectal, patch, pump or transdermal administration and the pharmaceutical compositions formulated accordingly. Parenteral administration includes intravenous, intraperitoneal, subcutaneous, intramuscular, transepithelial, nasal, intrapulmonary, intrathecal, rectal and topical modes of administration. Parenteral administration can be by continuous infusion over a selected period of time. The pharmaceutical composition of the disclosure is formulated to be compatible with its intended route of administration. In an embodiment, the composition is formulated in 26 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 accordance with routine procedures as a pharmaceutical composition adapted for intravenous, subcutaneous, intramuscular, oral, intranasal, or topical administration to human beings. In preferred embodiments, the pharmaceutical composition is formulated for intravenous administration. Typically, for oral therapeutic administration, Compound 1, or the pharmaceutically acceptable salt thereof may be incorporated with excipient and used in the form of ingestible tablets, buccal tablets, troches, capsules, elixirs, suspensions, syrups, wafers, and the like. Typically for parenteral administration, solutions of Compound 1, or the pharmaceutically acceptable salt thereof can generally be prepared in water suitably mixed with a surfactant such as hydroxypropylcellulose. Dispersions can also be prepared in glycerol, liquid polyethylene glycols, DMSO and mixtures thereof with or without alcohol, and in oils. Under ordinary conditions of storage and use, these preparations contain a preservative to prevent the growth of microorganisms. Typically, for injectable use, sterile aqueous solutions or dispersion of, and sterile powders of, Compound 1, or the pharmaceutically acceptable salt thereof for the extemporaneous preparation of sterile injectable solutions or dispersions are appropriate. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 5 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 10 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 15 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 20 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 25 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 30 mg. 27 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 35 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 40 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 45 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 50 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 55 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 60 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 65 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 70 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 75 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 80 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 85 mg. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 90 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 95 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 100 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 110 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 120 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 130 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 140 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 150 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 160 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 170 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 180 mg. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 190 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 200 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 220 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 240 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 260 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 280 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 300 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 320 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 340 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 360 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 380 mg. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 400 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 420 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 440 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 460 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 480 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 500 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 520 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 540 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 560 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 580 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 600 mg. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 620 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 640 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 660 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 680 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 700 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 20±2 mg, 20±1.8 mg, 20±1.6 mg, 20±1.5 mg, 20±1.4 mg, 15±1.3 mg, 20±1.2 mg, 20±1.1 mg, 20±1 mg, 20±0.9 mg, 20±0.8 mg, 20±0.7 mg, 20±0.6 mg, 20±0.5 mg, 20±0.4 mg, 20±0.3 mg, 20±0.2 mg, or 20±0.1 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 40±2 mg, 40±1.8 mg, 40±1.6 mg, 40±1.5 mg, 40±1.4 mg, 40±1.3 mg, 40±1.2 mg, 40±1.1 mg, 40±1 mg, 40±0.9 mg, 40±0.8 mg, 40±0.7 mg, 40±0.6 mg, 40±0.5 mg, 40±0.4 mg, 40±0.3 mg, 40±0.2 mg, or 40±0.1 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 80±5 mg, 80±4.5 mg, 80±4 mg, 80±3.5 mg, 80±3 mg, 80±2.5 mg, 80±2 mg, 80±1.5 mg, 80±1 mg, 80±0.9 mg, 80±0.8 mg, 80±0.7 mg, 80±0.6 mg, 80±0.5 mg, 80±0.4 mg, 80±0.3 mg, 80±0.2 mg, or 80±0.1 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 160±10 mg, 160±9 mg, 160±8 mg, 160±7 mg, 160±6 mg, 160±5 mg, 160±4.5 mg, 160±4.0 mg, 160±3.5 mg, 160±3.0 mg, mg, 160±2.0 mg, 160±1.5 mg, 160±1.0 mg, 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 160±0.9 mg, 160±0.8 mg, 160±0.7 mg, 160±0.6 mg, 160±0.5 mg, 160±0.4 mg, 160±0.3 mg, 160±0.2 mg, or 160±0.1 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 200±10 mg, 200±9 mg, 200±8 mg, 200±7 mg, 200±6 mg, 200±5 mg, 200±4.5 mg, 200±4.0 mg, 200±3.5 mg, 200±3.0 mg, 200±2.5 mg, 200±2.0 mg, 200±1.5 mg, 200±1.0 mg, 200±0.9 mg, 200±0.8 mg, 200±0.7 mg, 200±0.6 mg, 200±0.5 mg, 200±0.4 mg, 200±0.3 mg, 200±0.2 mg, or 200±0.1 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 320±10 mg, 320±9 mg, 320±8 mg, 320±7 mg, 320±6 mg, 320±5 mg, 320±4.5 mg, 320±4.0 mg, 320±3.5 mg, 320±3.0 mg, 320±2.5 mg, 320±2.0 mg, 320±1.5 mg, 320±1.0 mg, 320±0.9 mg, 320±0.8 mg, 320±0.7 mg, 320±0.6 mg, 320±0.5 mg, 320±0.4 mg, 320±0.3 mg, 320±0.2 mg, or 320±0.1 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 400±10 mg, 400±9 mg, 400±8 mg, 400±7 mg, 400±6 mg, 400±5 mg, 400±4.5 mg, 400±4.0 mg, 400±3.5 mg, 400±3.0 mg, 400±2.5 mg, 400±2.0 mg, 400±1.5 mg, 400±1.0 mg, 400±0.9 mg, 400±0.8 mg, 400±0.7 mg, 400±0.6 mg, 400±0.5 mg, 400±0.4 mg, 400±0.3 mg, 400±0.2 mg, or 400±0.1 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 500±10 mg, 500±9 mg, 500±8 mg, 500±7 mg, 500±6 mg, 500±5 mg, 500±4.5 mg, 500±4.0 mg, 500±3.5 mg, 500±3.0 mg, 500±2.5 mg, 500±2.0 mg, 500±1.5 mg, 500±1.0 mg, 500±0.9 mg, 500±0.8 mg, 500±0.7 mg, 500±0.6 mg, 500±0.5 mg, 500±0.4 mg, 500±0.3 mg, 500±0.2 mg, or 500±0.1 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 5 mg to about 700 mg, about 5 mg to about 650 mg, about 5 mg to about 600 mg, about 5 mg to about 550 mg, about 5 mg to about 500 mg, about 5 mg to about 450 mg, about 5 mg to about 400 mg, about 5 mg to about 350 mg, about 5 mg to about 300 mg, about 5 mg to about 250 mg, about 5 mg to about 200 mg, about 5 mg to about 150 mg, about 5 mg to about 140 mg, about 5 mg to about 130 mg, about 5 mg to about 120 mg, about 5 mg to about 100 mg, about 5 mg to about 90 mg, about 5 mg to about 80 mg, about 5 mg to about 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 70 mg, about 5 mg to about 60 mg, about 5 mg to about 50 mg, about 5 mg to about 45 mg, about 5 mg to about 40 mg, about 5 mg to about 35 mg, about 5 mg to about 30 mg, about 5 mg to about 25 mg, or about 5 mg to about 20 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 20 mg to about 700 mg, about 25 mg to about 700 mg, about 30 mg to about 700 mg, about 35 mg to about 700 mg, about 40 mg to about 700 mg, about 45 mg to about 700 mg, about 50 mg to about 700 mg, about 60 mg to about 700 mg, about 70 mg to about 700 mg, about 80 mg to about 700 mg, about 90 mg to about 700 mg, about 100 mg to about 700 mg, about 110 mg to about 700 mg, about 120 mg to about 700 mg, about 130 mg to about 700 mg, about 140 mg to about 700 mg, about 150 mg to about 700 mg, about 200 mg to about 700 mg, about 250 mg to about 700 mg, about 300 mg to about 700 mg, about 350 mg to about 700 mg, about 400 mg to about 700 mg, about 450 mg to about 700 mg, about 500 mg to about 700 mg, about 550 mg to about 700 mg, about 600 mg to about 700 mg, or about 650 mg to about 700 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 20 mg to about 600 mg, about 25 mg to about 600 mg, about 30 mg to about 600 mg, about 35 mg to about 600 mg, about 40 mg to about 600 mg, about 45 mg to about 600 mg, about 50 mg to about 600 mg, about 60 mg to about 600 mg, about 70 mg to about 600 mg, about 80 mg to about 600 mg, about 90 mg to about 600 mg, about 100 mg to about 600 mg, about 110 mg to about 600 mg, about 120 mg to about 600 mg, about 130 mg to about 600 mg, about 140 mg to about 600 mg, about 150 mg to about 600 mg, about 200 mg to about 600 mg, about 250 mg to about 600 mg, about 300 mg to about 600 mg, about 350 mg to about 600 mg, about 400 mg to about 600 mg, about 450 mg to about 600 mg, about 500 mg to about 600 mg, or about 550 mg to about 600 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 20 mg to about 500 mg, about 25 mg to about 500 mg, about 30 mg to about 500 mg, about 35 mg to about 500 mg, about 40 mg to about 500 mg, about 45 mg to about 500 mg, about 50 mg to about 500 mg, about 60 mg to about 500 mg, about 70 mg to about 500 mg, about 80 mg to about 500 mg, about 90 mg to about 500 mg, about 100 mg to about 500 mg, about 110 mg to about 500 mg, about 120 mg to about 500 mg, about 130 mg to about 500 mg, about 140 mg to about 500 mg, about 150 mg to about 500 mg, about 200 34 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 mg to about 500 mg, about 250 mg to about 500 mg, about 300 mg to about 500 mg, about 350 mg to about 500 mg, about 400 mg to about 500 mg, or about 450 mg to about 500 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 20 mg to about 400 mg, about 25 mg to about 400 mg, about 30 mg to about 400 mg, about 35 mg to about 400 mg, about 40 mg to about 400 mg, about 45 mg to about 400 mg, about 50 mg to about 400 mg, about 60 mg to about 400 mg, about 70 mg to about 400 mg, about 80 mg to about 400 mg, about 90 mg to about 400 mg, about 100 mg to about 400 mg, about 110 mg to about 400 mg, about 120 mg to about 400 mg, about 130 mg to about 400 mg, about 140 mg to about 400 mg, about 150 mg to about 400 mg, about 200 mg to about 400 mg, about 250 mg to about 400 mg, about 300 mg to about 400 mg, or about 350 mg to about 400 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 20 mg to about 300 mg, about 25 mg to about 300 mg, about 30 mg to about 300 mg, about 35 mg to about 300 mg, about 40 mg to about 300 mg, about 45 mg to about 300 mg, about 50 mg to about 300 mg, about 60 mg to about 300 mg, about 70 mg to about 300 mg, about 80 mg to about 300 mg, about 90 mg to about 300 mg, about 100 mg to about 300 mg, about 110 mg to about 300 mg, about 120 mg to about 300 mg, about 130 mg to about 300 mg, about 140 mg to about 300 mg, about 150 mg to about 300 mg, about 200 mg to about 300 mg, or about 250 mg to about 300 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 20 mg to about 200 mg, about 25 mg to about 200 mg, about 30 mg to about 200 mg, about 35 mg to about 200 mg, about 40 mg to about 200 mg, about 45 mg to about 200 mg, about 50 mg to about 200 mg, about 60 mg to about 200 mg, about 70 mg to about 200 mg, about 80 mg to about 200 mg, about 90 mg to about 200 mg, about 100 mg to about 200 mg, about 110 mg to about 200 mg, about 120 mg to about 200 mg, about 130 mg to about 200 mg, about 140 mg to about 200 mg, about 150 mg to about 200 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 20 mg to about 150 mg, about 25 mg to about 150 mg, about 30 mg to about 150 mg, about 35 mg to about 150 mg, about 40 mg to about 150 mg, about 45 mg to about 150 mg, about 50 mg to about 150 mg, about 60 mg to about 150 mg, about 70 mg to 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 about 150 mg, about 80 mg to about 150 mg, about 90 mg to about 150 mg, about 100 mg to about 150 mg, about 110 mg to about 150 mg, about 120 mg to about 150 mg, about 130 mg to about 150 mg, or about 140 mg to about 150 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 20 mg to about 100 mg, about 25 mg to about 100 mg, about 30 mg to about 100 mg, about 35 mg to about 100 mg, about 40 mg to about 100 mg, about 45 mg to about 100 mg, about 50 mg to about 100 mg, about 60 mg to about 100 mg, about 70 mg to about 100 mg, about 80 mg to about 100 mg, or about 90 mg to about 100 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 5 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 10 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 15 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 20 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 25 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 30 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 35 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 40 mg / day. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 45 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 50 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 55 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 60 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 65 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 70 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 75 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 80 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 85 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 90 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 95 mg / day. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 100 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 110 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 120 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 130 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 140 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 150 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 160 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 170 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 180 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 190 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 200 mg / day. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 220 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 240 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 260 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 280 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 300 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 320 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 340 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 360 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 380 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 400 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 420 mg / day. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 440 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 460 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 480 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 500 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 520 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 540 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 560 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 580 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 600 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 620 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 640 mg / day. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 660 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 680 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage of about 700 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 5 mg / day to about 700 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 5 mg / day to about 600 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 5 mg / day to about 500 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 5 mg / day to about 400 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 5 mg / day to about 300 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 5 mg / day to about 200 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 5 mg / day to about 100 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 5 mg / day to about 95 mg / day. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 5 mg / day to about 90 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 5 mg / day to about 85 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 5 mg / day to about 80 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 5 mg / day to about 75 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 5 mg / day to about 70 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 5 mg / day to about 65 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 5 mg / day to about 60 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 5 mg / day to about 55 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 5 mg / day to about 50 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 5 mg / day to about 45 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 5 mg / day to about 40 mg / day. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 5 mg / day to about 35 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 5 mg / day to about 30 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about5 mg / day to about 25 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 5 mg / day to about 20 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 10 mg / day to about 700 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 15 mg / day to about 700 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 20 mg / day to about 700 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 25 mg / day to about 700 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 30 mg / day to about 700 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 35 mg / day to about 700 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 40 mg / day to about 700 mg / day. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 45 mg / day to about 700 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 50 mg / day to about 700 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 55 mg / day to about 700 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 60 mg / day to about 700 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 65 mg / day to about 700 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 70 mg / day to about 700 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 75 mg / day to about 700 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 80 mg / day to about 700 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 85 mg / day to about 700 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 90 mg / day to about 700 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 95 mg / day to about 700 mg / day. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 100 mg / day to about 700 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 200 mg / day to about 700 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 300 mg / day to about 700 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 400 mg / day to about 700 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 500 mg / day to about 700 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a dosage ranging from about 600 mg / day to about 700 mg / day. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered orally. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once daily. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once daily at a dosage of about 700 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once daily at a dosage of about 600 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once daily at a dosage of about 500 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once daily at a dosage of about 400 mg. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once daily at a dosage of about 320 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once daily at a dosage of about 300 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once daily at a dosage of about 200 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once daily at a dosage of about 180 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once daily at a dosage of about 160 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once daily at a dosage of about 140 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once daily at a dosage of about 120 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once daily at a dosage of about 100 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once daily at a dosage of about 80 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once daily at a dosage of about 60 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once daily at a dosage of about 40 mg. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once daily at a dosage of about 20 mg. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once daily, for example, at any of the dosage described herein, under fed conditions, wherein the difference between AUCinfof Compound 1 if administered under fed conditions and AUCinfof Compound 1 if administered under fasted conditions is less than about 15%, less than about 20%, less than about 25%, less than about 30%, less than about 35%, less than about 40%, or less than about 45%. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once daily, for example, at any of the dosage described herein, under fed conditions, wherein the difference between AUCinf of Compound 1 if administered under fed conditions and AUCinf of Compound 1 if administered under fasted conditions is about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, or about 17%, about 18%, about 19%, about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, or about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, or about 37%, about 38%, about 39%, about 40%, about 41%, about 42%, about 43%, about 44%, or about 45%. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once daily, for example, at any of the dosage described herein, under fasted conditions, wherein the difference between AUCinfof Compound 1 if administered under fed conditions and AUCinfof Compound 1 if administered under fasted conditions is less than about 15%, less than about 20%, less than about 25%, less than about 30%, less than about 35%, less than about 40%, or less than about 45%. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once daily, for example, at any of the dosage described herein, under fasted conditions, wherein the difference between AUCinf of Compound 1 if administered under fed conditions and AUCinf of Compound 1 if administered under fasted conditions is about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, or about 17%, about 18%, about 19%, about 20%, about 21%, about 22%, about 47 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 23%, about 24%, about 25%, about 26%, or about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, or about 37%, about 38%, about 39%, about 40%, about 41%, about 42%, about 43%, about 44%, or about 45%. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once daily, for example, at any of the dosage described herein, under fed conditions, wherein the difference between Cmaxof Compound 1 if administered under fed conditions and Cmaxof Compound 1 if administered under fasted conditions is less than about 35%, less than about 38%, less than about 40%, less than about 45%, less than about 50%, less than about 55%, or less than about 60%. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once daily, for example, at any of the dosage described herein, under fed conditions, wherein the difference between Cmax of Compound 1 if administered under fed conditions and Cmax of Compound 1 if administered under fasted conditions is about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, or about 17%, about 18%, about 19%, about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, or about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, or about 37%, about 38%, about 39%, about 40%, about 41%, about 42%, about 43%, about 44%, about 45%, about 46%, or about 47%, about 48%, about 49%, about 50%, about 51%, about 52%, about 53%, about 54%, about 55%, about 56%, or about 57%, about 58%, about 59%, or about 60%. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once daily, for example, at any of the dosage described herein, under fasted conditions, wherein the difference between Cmax of Compound 1 if administered under fed conditions and Cmax of Compound 1 if administered under fasted conditions is less than about 35%, less than about 38%, less than about 40%, less than about 45%, less than about 50%, less than about 55%, or less than about 60%. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once daily, for example, at any of the dosage described herein, under fasted conditions, wherein the difference between Cmax of Compound 1 if administered under fed conditions and Cmax of Compound 1 if administered under fasted conditions is about 10%, about 11%, about 12%, 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 about 13%, about 14%, about 15%, about 16%, or about 17%, about 18%, about 19%, about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, or about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, or about 37%, about 38%, about 39%, about 40%, about 41%, about 42%, about 43%, about 44%, about 45%, about 46%, or about 47%, about 48%, about 49%, about 50%, about 51%, about 52%, about 53%, about 54%, about 55%, about 56%, or about 57%, about 58%, about 59%, or about 60%. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered at a dosage of between about 5 mg and about 700 mg, and wherein the difference between AUCinf of Compound 1 if administered under fed conditions and AUCinf of Compound 1 if administered under fasted conditions is less than about 40%. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered at a dosage of between about 5 mg and about 700 mg, and wherein the difference between AUCinfof Compound 1 if administered under fed conditions and AUCinfof Compound 1 if administered under fasted conditions is less than about 35%. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered at a dosage of between about 5 mg and about 700 mg, and wherein the difference between AUCinf of Compound 1 if administered under fed conditions and AUCinf of Compound 1 if administered under fasted conditions is less than about 30%. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered at a dosage of between about 5 mg and about 700 mg, and wherein the difference between AUCinf of Compound 1 if administered 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 under fed conditions and AUCinf of Compound 1 if administered under fasted conditions is less than about 25%. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered at a dosage of between about 5 mg and about 700 mg, and wherein the difference between AUCinfof Compound 1 if administered under fed conditions and AUCinfof Compound 1 if administered under fasted conditions is less than about 20%. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered at a dosage of between about 5 mg and about 700 mg, and wherein the difference between AUCinf of Compound 1 if administered under fed conditions and AUCinf of Compound 1 if administered under fasted conditions is less than about 15%. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered at a dosage of between about 5 mg and about 700 mg, and wherein the difference between AUCinfof Compound 1 if administered under fed conditions and AUCinfof Compound 1 if administered under fasted conditions is about 5%, about 10%, about 11%, about 15%, about 20%, about 25%, about 30%, about 35%, or about 40%. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered at a dosage of between about 5 mg and about 700 mg, and wherein the difference between Cmax of Compound 1 if administered under fed conditions and Cmax of Compound 1 if administered under fasted conditions is less than about 60%. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 Compound 1, wherein Compound 1 is administered at a dosage of between about 5 mg and about 700 mg, and wherein the difference between Cmax of Compound 1 if administered under fed conditions and Cmax of Compound 1 if administered under fasted conditions is less than about 55%. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered at a dosage of between about 5 mg and about 700 mg, and wherein the difference between Cmaxof Compound 1 if administered under fed conditions and Cmaxof Compound 1 if administered under fasted conditions is less than about 50%. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered at a dosage of between about 5 mg and about 700 mg, and wherein the difference between Cmax of Compound 1 if administered under fed conditions and Cmax of Compound 1 if administered under fasted conditions is less than about 45%. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered at a dosage of between about 5 mg and about 700 mg, and wherein the difference between Cmaxof Compound 1 if administered under fed conditions and Cmaxof Compound 1 if administered under fasted conditions is less than about 40%. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered at a dosage of between about 5 mg and about 700 mg, and wherein the difference between Cmax of Compound 1 if administered under fed conditions and Cmax of Compound 1 if administered under fasted conditions is about 35%, about 38%, about 40%, about 45%, about 50%, about 55%, or about 60%. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or 51 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the AUCinf of Compound 1 is from about 200 ng*h / mL to about 1,500 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the AUCinfof Compound 1 is from about 250 ng*h / mL to about 1,300 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the AUCinf of Compound 1 is from about 300 ng*h / mL to about 1,100 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the AUCinfof Compound 1 is from about 350 ng*h / mL to about 900 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the AUCinf of Compound 1 is from about 400 ng*h / mL to about 800 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the AUCinf of Compound 1 is from about 450 ng*h / mL to about 700 ng*h / mL. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the AUCinfof Compound 1 is from about 500 ng*h / mL to about 650 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the AUCinf of Compound 1 is from about 500 ng*h / mL to about 600 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fed conditions, wherein after administration the AUCinf of Compound 1 is from about 100 ng*h / mL to about 1,500 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fed conditions, wherein after administration the AUCinfof Compound 1 is from about 250 ng*h / mL to about 1,300 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fed conditions, wherein after administration the AUCinf of Compound 1 is from about 300 ng*h / mL to about 1,100 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 fed conditions, wherein after administration the AUCinf of Compound 1 is from about 350 ng*h / mL to about 900 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fed conditions, wherein after administration the AUCinfof Compound 1 is from about 400 ng*h / mL to about 800 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fed conditions, wherein after administration the AUCinf of Compound 1 is from about 450 ng*h / mL to about 700 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fed conditions, wherein after administration the AUCinfof Compound 1 is from about 500 ng*h / mL to about 650 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fed conditions, wherein after administration the AUCinfof Compound 1 is from about 500 ng*h / mL to about 600 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the AUCinf of Compound 1 is from about 1,500 ng*h / mL to about 2,800 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or 54 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the AUCinf of Compound 1 is from about 1,600 ng*h / mL to about 2,700 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the AUCinfof Compound 1 is from about 1,700 ng*h / mL to about 2,600 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the AUCinf of Compound 1 is from about 1,800 ng*h / mL to about 2,500 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the AUCinfof Compound 1 is from about 1,900 ng*h / mL to about 2,400 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the AUCinf of Compound 1 is from about 1,950 ng*h / mL to about 2,300 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the AUCinf of Compound 1 is from about 2,000 ng*h / mL to about 2,200 ng*h / mL. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the AUCinfof Compound 1 is from about 1,000 ng*h / mL to about 2,800 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the AUCinf of Compound 1 is from about 1,200 ng*h / mL to about 2,700 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the AUCinf of Compound 1 is from about 1,400 ng*h / mL to about 2,600 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the AUCinfof Compound 1 is from about 1,600 ng*h / mL to about 2,500 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the AUCinf of Compound 1 is from about 1,800 ng*h / mL to about 2,400 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 fed conditions, wherein after administration the AUCinf of Compound 1 is from about 1,900 ng*h / mL to about 2,300 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the AUCinfof Compound 1 is from about 2,000 ng*h / mL to about 2,200 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fasted conditions, wherein after administration the AUCinf of Compound 1 is from about 2,000 ng*h / mL to about 3,100 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fasted conditions, wherein after administration the AUCinfof Compound 1 is from about 2,100 ng*h / mL to about 3,000 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fasted conditions, wherein after administration the AUCinfof Compound 1 is from about 2,200 ng*h / mL to about 2,900 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fasted conditions, wherein after administration the AUCinf of Compound 1 is from about 2,250 ng*h / mL to about 2,800 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or 57 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fasted conditions, wherein after administration the AUCinf of Compound 1 is from about 2,300 ng*h / mL to about 2,750 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fasted conditions, wherein after administration the AUCinfof Compound 1 is from about 2,350 ng*h / mL to about 2,700 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fasted conditions, wherein after administration the AUCinf of Compound 1 is from about 2,400 ng*h / mL to about 2,650 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fasted conditions, wherein after administration the AUCinfof Compound 1 is from about 2,500 ng*h / mL to about 2,600 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fed conditions, wherein after administration the AUCinf of Compound 1 is from about 1,700 ng*h / mL to about 2,800 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fed conditions, wherein after administration the AUCinf of Compound 1 is from about 1,800 ng*h / mL to about 2,700 ng*h / mL. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fed conditions, wherein after administration the AUCinfof Compound 1 is from about 1,900 ng*h / mL to about 2,600 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fed conditions, wherein after administration the AUCinf of Compound 1 is from about 2,000 ng*h / mL to about 2,500 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fed conditions, wherein after administration the AUCinf of Compound 1 is from about 2,100 ng*h / mL to about 2,400 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fed conditions, wherein after administration the AUCinfof Compound 1 is from about 2,200 ng*h / mL to about 2,300 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the AUCinf of Compound 1 is from about 5,800 ng*h / mL to about 7,400 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 at fasted conditions, wherein after administration the AUCinf of Compound 1 is from about 5,900 ng*h / mL to about 7,300 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the AUCinfof Compound 1 is from about 6,000 ng*h / mL to about 7,200 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the AUCinf of Compound 1 is from about 6,100 ng*h / mL to about 7,100 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the AUCinfof Compound 1 is from about 6,200 ng*h / mL to about 7,000 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the AUCinfof Compound 1 is from about 6,300 ng*h / mL to about 6,900 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the AUCinf of Compound 1 is from about 6,400 ng*h / mL to about 6,800 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or 60 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the AUCinf of Compound 1 is from about 6,500 ng*h / mL to about 6,700 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the AUCinfof Compound 1 is from about 5,500 ng*h / mL to about 7,400 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the AUCinf of Compound 1 is from about 5,600 ng*h / mL to about 7,300 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the AUCinfof Compound 1 is from about 5,800 ng*h / mL to about 7,200 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the AUCinf of Compound 1 is from about 6,000 ng*h / mL to about 7,100 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the AUCinf of Compound 1 is from about 6,200 ng*h / mL to about 7,000 ng*h / mL. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the AUCinfof Compound 1 is from about 6,300 ng*h / mL to about 6,900 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the AUCinf of Compound 1 is from about 6,400 ng*h / mL to about 6,800 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the AUCinf of Compound 1 is from about 6,500 ng*h / mL to about 6,700 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the AUCinfof Compound 1 is about 200 ng*h / mL, about 250 ng*h / mL, about 300 ng*h / mL, about 350 ng*h / mL, about 400 ng*h / mL, about 450 ng*h / mL, about 500 ng*h / mL, about 550 ng*h / mL, about 553 ng*h / mL, about 600 ng*h / mL, about 650 ng*h / mL, about 700 ng*h / mL, about 750 ng*h / mL, about 800 ng*h / mL, about 850 ng*h / mL, about 900 ng*h / mL, about 950 ng*h / mL, about 1,000 ng*h / mL, about 1,050 ng*h / mL, about 1,100 ng*h / mL, about 1,150 ng*h / mL, about 1,200 ng*h / mL, about 1,250 ng*h / mL, about 1,300 ng*h / mL, about 1,350 ng*h / mL, about 1,400 ng*h / mL, about 1,450 ng*h / mL, or about 1,500 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 fed conditions, wherein after administration the AUCinf of Compound 1 is about 100 ng*h / mL, about 150 ng*h / mL, about 200 ng*h / mL, about 250 ng*h / mL, about 300 ng*h / mL, about 350 ng*h / mL, about 400 ng*h / mL, about 450 ng*h / mL, about 500 ng*h / mL, about 550 ng*h / mL, about 600 ng*h / mL, about 650 ng*h / mL, about 700 ng*h / mL, about 750 ng*h / mL, about 800 ng*h / mL, about 850 ng*h / mL, about 900 ng*h / mL, about 950 ng*h / mL, about 1,000 ng*h / mL, about 1,050 ng*h / mL, about 1,100 ng*h / mL, about 1,150 ng*h / mL, about 1,200 ng*h / mL, about 1,250 ng*h / mL, about 1,300 ng*h / mL, about 1,350 ng*h / mL, about 1,400 ng*h / mL, about 1,450 ng*h / mL, or about 1,500 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the AUCinf of Compound 1 is about 1,500 ng*h / mL, about 1,550 ng*h / mL, about 1,600 ng*h / mL, about 1,650 ng*h / mL, about 1,700 ng*h / mL, about 1,750 ng*h / mL, about 1,800 ng*h / mL, about 1,850 ng*h / mL, about 1,900 ng*h / mL, about 1,950 ng*h / mL, about 2,000 ng*h / mL, about 2,050 ng*h / mL, about 2,070 ng*h / mL, about 2,100 ng*h / mL, about 2,150 ng*h / mL, about 2,200 ng*h / mL, about 2,250 ng*h / mL, about 2,300 ng*h / mL, about 2,350 ng*h / mL, about 2,400 ng*h / mL, about 2,450 ng*h / mL, about 2,500 ng*h / mL, about 2,550 ng*h / mL, about 2,600 ng*h / mL, about 2,650 ng*h / mL, about 2,700 ng*h / mL, about 2,750 ng*h / mL, or about 2,800 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the AUCinfof Compound 1 is about 1,000 ng*h / mL, about 1,050 ng*h / mL, about 1,100 ng*h / mL, about 1,150 ng*h / mL, about 1,200 ng*h / mL, about 1,250 ng*h / mL, about 1,300 ng*h / mL, about 1,350 ng*h / mL, about 1,400 ng*h / mL, about 1,450 ng*h / mL, about 1,500 ng*h / mL, about 1,550 ng*h / mL, about 1,600 ng*h / mL, about 1,650 ng*h / mL, about 1,700 ng*h / mL, about 1,750 ng*h / mL, about 1,800 ng*h / mL, about 1,850 ng*h / mL, about 1,900 ng*h / mL, about 1,950 ng*h / mL, about 2,000 ng*h / mL, about 2,050 ng*h / mL, about 2,100 ng*h / mL, about 2,150 ng*h / mL, about 2,200 ng*h / mL, about 2,250 ng*h / mL, about 2,300 ng*h / mL, about 2,350 ng*h / mL, about 2,400 ng*h / mL, about 2,450 ng*h / mL, about 2,500 ng*h / mL, about 2,550 ng*h / mL, about 2,600 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 ng*h / mL, about 2,650 ng*h / mL, about 2,700 ng*h / mL, about 2,750 ng*h / mL, or about 2,800 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fasted conditions, wherein after administration the AUCinfof Compound 1 is about 2,000 ng*h / mL, about 2,050 ng*h / mL, about 2,100 ng*h / mL, about 2,150 ng*h / mL, about 2,200 ng*h / mL, about 2,250 ng*h / mL, about 2,300 ng*h / mL, about 2,350 ng*h / mL, about 2,400 ng*h / mL, about 2,450 ng*h / mL, about 2,500 ng*h / mL, about 2,550 ng*h / mL, about 2,560 ng*h / mL, about 2,600 ng*h / mL, about 2,650 ng*h / mL, about 2,700 ng*h / mL, about 2,750 ng*h / mL, about 2,800 ng*h / mL, about 2,850 ng*h / mL, about 2,900 ng*h / mL, about 2,950 ng*h / mL, about 3,000 ng*h / mL, about 3,050 ng*h / mL, or about 3,100 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fed conditions, wherein after administration the AUCinf of Compound 1 is about 1,700 ng*h / mL, about 1,750 ng*h / mL, about 1,800 ng*h / mL, about 1,850 ng*h / mL, about 1,900 ng*h / mL, about 1,950 ng*h / mL, about 2,000 ng*h / mL, about 2,050 ng*h / mL, about 2,100 ng*h / mL, about 2,150 ng*h / mL, about 2,200 ng*h / mL, about 2,250 ng*h / mL, about 2,300 ng*h / mL, about 2,350 ng*h / mL, about 2,400 ng*h / mL, about 2,450 ng*h / mL, about 2,500 ng*h / mL, about 2,550 ng*h / mL, about 2,560 ng*h / mL, about 2,600 ng*h / mL, about 2,650 ng*h / mL, about 2,700 ng*h / mL, about 2,750 ng*h / mL, or about 2,800 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the AUCinf of Compound 1 is about 5,800 ng*h / mL, about 5,850 ng*h / mL, about 5,900 ng*h / mL, about 5,950 ng*h / mL, about 6,000 ng*h / mL, about 6,050 ng*h / mL, about 6,100 ng*h / mL, about 6,150 ng*h / mL, about 6,200 ng*h / mL, about 6,250 ng*h / mL, about 6,300 ng*h / mL, about 6,350 ng*h / mL, about 6,400 ng*h / mL, about 6,450 ng*h / mL, about 6,500 ng*h / mL, about 6,550 ng*h / mL, about 6,560 ng*h / mL, about 6,600 ng*h / mL, about 6,650 ng*h / mL, about 6,700 ng*h / mL, about 6,750 64 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 ng*h / mL, about 6,800 ng*h / mL, about 6,850 ng*h / mL, about 6,900 ng*h / mL, about 6,950 ng*h / mL, about 7,000 ng*h / mL, about 7,050 ng*h / mL, about 7,100 ng*h / mL, about 7,150 ng*h / mL, about 7,200 ng*h / mL, about 7,250 ng*h / mL, about 7,300 ng*h / mL, about 7,350 ng*h / mL, or about 7,400 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the AUCinfof Compound 1 is about 5,500 ng*h / mL, about 5,550 ng*h / mL, about 5,600 ng*h / mL, about 5,650 ng*h / mL, about 5,700 ng*h / mL, about 5,750 ng*h / mL, about 5,800 ng*h / mL, about 5,850 ng*h / mL, about 5,900 ng*h / mL, about 5,950 ng*h / mL, about 6,000 ng*h / mL, about 6,050 ng*h / mL, about 6,100 ng*h / mL, about 6,150 ng*h / mL, about 6,200 ng*h / mL, about 6,250 ng*h / mL, about 6,300 ng*h / mL, about 6,350 ng*h / mL, about 6,400 ng*h / mL, about 6,450 ng*h / mL, about 6,500 ng*h / mL, about 6,550 ng*h / mL, about 6,560 ng*h / mL, about 6,600 ng*h / mL, about 6,650 ng*h / mL, about 6,700 ng*h / mL, about 6,750 ng*h / mL, about 6,800 ng*h / mL, about 6,850 ng*h / mL, about 6,900 ng*h / mL, about 6,950 ng*h / mL, about 7,000 ng*h / mL, about 7,050 ng*h / mL, about 7,100 ng*h / mL, about 7,150 ng*h / mL, about 7,200 ng*h / mL, about 7,250 ng*h / mL, about 7,300 ng*h / mL, about 7,350 ng*h / mL, or about 7,400 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the Cmaxof Compound 1 is from about 25 ng / mL to about 240 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the Cmax of Compound 1 is from about 30 ng / mL to about 230 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the Cmax of Compound 1 is from about 35 ng / mL to about 220 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the Cmaxof Compound 1 is from about 40 ng / mL to about 210 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the Cmax of Compound 1 is from about 45 ng / mL to about 200 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the Cmaxof Compound 1 is from about 50 ng / mL to about 190 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the Cmax of Compound 1 is from about 55 ng / mL to about 180 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the Cmax of Compound 1 is from about 60 ng / mL to about 170 ng / mL. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the Cmaxof Compound 1 is from about 65 ng / mL to about 160 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the Cmax of Compound 1 is from about 70 ng / mL to about 150 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fed conditions, wherein after administration the Cmax of Compound 1 is from about 25 ng / mL to about 240 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fed conditions, wherein after administration the Cmaxof Compound 1 is from about 30 ng / mL to about 230 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fed conditions, wherein after administration the Cmax of Compound 1 is from about 35 ng / mL to about 220 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 fed conditions, wherein after administration the Cmax of Compound 1 is from about 40 ng / mL to about 210 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fed conditions, wherein after administration the Cmaxof Compound 1 is from about 45 ng / mL to about 200 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fed conditions, wherein after administration the Cmax of Compound 1 is from about 50 ng / mL to about 190 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fed conditions, wherein after administration the Cmaxof Compound 1 is from about 55 ng / mL to about 180 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fed conditions, wherein after administration the Cmaxof Compound 1 is from about 60 ng / mL to about 170 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fed conditions, wherein after administration the Cmax of Compound 1 is from about 65 ng / mL to about 160 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or 68 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fed conditions, wherein after administration the Cmax of Compound 1 is from about 70 ng / mL to about 150 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the Cmaxof Compound 1 is from about 200 ng / mL to about 450 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the Cmax of Compound 1 is from about 205 ng / mL to about 440 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the Cmaxof Compound 1 is from about 210 ng / mL to about 430 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the Cmax of Compound 1 is from about 215 ng / mL to about 420 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the Cmax of Compound 1 is from about 220 ng / mL to about 410 ng / mL. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the Cmaxof Compound 1 is from about 225 ng / mL to about 400 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the Cmax of Compound 1 is from about 230 ng / mL to about 390 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the Cmax of Compound 1 is from about 235 ng / mL to about 380 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the Cmaxof Compound 1 is from about 240 ng / mL to about 370 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the Cmax of Compound 1 is from about 245 ng / mL to about 360 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 fasted conditions, wherein after administration the Cmax of Compound 1 is from about 250 ng / mL to about 350 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the Cmaxof Compound 1 is from about 180 ng / mL to about 470 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the Cmax of Compound 1 is from about 190 ng / mL to about 460 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the Cmaxof Compound 1 is from about 200 ng / mL to about 450 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the Cmaxof Compound 1 is from about 205 ng / mL to about 440 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the Cmax of Compound 1 is from about 210 ng / mL to about 430 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or 71 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the Cmax of Compound 1 is from about 215 ng / mL to about 420 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the Cmaxof Compound 1 is from about 220 ng / mL to about 410 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the Cmax of Compound 1 is from about 225 ng / mL to about 400 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the Cmaxof Compound 1 is from about 230 ng / mL to about 390 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the Cmax of Compound 1 is from about 235 ng / mL to about 380 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the Cmax of Compound 1 is from about 240 ng / mL to about 370 ng / mL. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the Cmaxof Compound 1 is from about 245 ng / mL to about 360 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the Cmax of Compound 1 is from about 250 ng / mL to about 350 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fasted conditions, wherein after administration the Cmax of Compound 1 is from about 305 ng / mL to about 550 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fasted conditions, wherein after administration the Cmaxof Compound 1 is from about 310 ng / mL to about 540 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fasted conditions, wherein after administration the Cmax of Compound 1 is from about 315 ng / mL to about 530 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 fasted conditions, wherein after administration the Cmax of Compound 1 is from about 320 ng / mL to about 520 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fasted conditions, wherein after administration the Cmaxof Compound 1 is from about 325 ng / mL to about 510 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fasted conditions, wherein after administration the Cmax of Compound 1 is from about 330 ng / mL to about 500 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fasted conditions, wherein after administration the Cmaxof Compound 1 is from about 335 ng / mL to about 490 ng / mL.In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fasted conditions, wherein after administration the Cmaxof Compound 1 is from about 340 ng / mL to about 480 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fasted conditions, wherein after administration the Cmax of Compound 1 is from about 345 ng / mL to about 470 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fasted conditions, wherein after administration the Cmax of Compound 1 is from about 350 ng / mL to about 460 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fed conditions, wherein after administration the Cmaxof Compound 1 is from about 160 ng / mL to about 420 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fed conditions, wherein after administration the Cmax of Compound 1 is from about 165 ng / mL to about 410 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fed conditions, wherein after administration the Cmaxof Compound 1 is from about 170 ng / mL to about 400 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fed conditions, wherein after administration the Cmax of Compound 1 is from about 175 ng / mL to about 390 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fed conditions, wherein after administration the Cmax of Compound 1 is from about 180 ng / mL to about 380 ng / mL. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fed conditions, wherein after administration the Cmaxof Compound 1 is from about 185 ng / mL to about 370 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fed conditions, wherein after administration the Cmax of Compound 1 is from about 190 ng / mL to about 360 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fed conditions, wherein after administration the Cmax of Compound 1 is from about 195 ng / mL to about 350 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fed conditions, wherein after administration the Cmaxof Compound 1 is from about 200 ng / mL to about 340 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fed conditions, wherein after administration the Cmax of Compound 1 is from about 200 ng / mL to about 330 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 at fasted conditions, wherein after administration the Cmax of Compound 1 is from about 450 ng / mL to about 1,650 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the Cmaxof Compound 1 is from about 500 ng / mL to about 1,550 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the Cmax of Compound 1 is from about 550 ng / mL to about 1,450 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the Cmaxof Compound 1 is from about 600 ng / mL to about 1,350 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the Cmaxof Compound 1 is from about 650 ng / mL to about 1,250 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the Cmax of Compound 1 is from about 700 ng / mL to about 1,150 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or 77 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the Cmax of Compound 1 is from about 750 ng / mL to about 1,050 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the Cmaxof Compound 1 is from about 800 ng / mL to about 950 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the Cmax of Compound 1 is from about 350 ng / mL to about 1,850 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the Cmaxof Compound 1 is from about 400 ng / mL to about 1,750 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the Cmax of Compound 1 is from about 450 ng / mL to about 1,650 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the Cmax of Compound 1 is from about 500 ng / mL to about 1,550 ng / mL. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the Cmaxof Compound 1 is from about 550 ng / mL to about 1,450 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the Cmax of Compound 1 is from about 600 ng / mL to about 1,350 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the Cmax of Compound 1 is from about 650 ng / mL to about 1,250 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the Cmaxof Compound 1 is from about 700 ng / mL to about 1,150 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the Cmax of Compound 1 is from about 750 ng / mL to about 1,050 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 at fed conditions, wherein after administration the Cmax of Compound 1 is from about 800 ng / mL to about 950 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the Cmaxof Compound 1 is about 25 ng / mL, about 30 ng / mL, about 35 ng / mL, about 40 ng / mL, about 45 ng / mL, about 50 ng / mL, about 55 ng / mL, about 60 ng / mL, about 65 ng / mL, about 70 ng / mL, about 75 ng / mL, about 80 ng / mL, about 85 ng / mL, about 90 ng / mL, about 95 ng / mL, about 100 ng / mL, about 105 ng / mL, about 110 ng / mL, about 111 ng / mL, about 115 ng / mL, about 120 ng / mL, about 125 ng / mL, about 130 ng / mL, about 135 ng / mL, about 140 ng / mL, about 145 ng / mL, about 150 ng / mL, about 155 ng / mL, about 160 ng / mL, about 165 ng / mL, about 170 ng / mL, about 175 ng / mL, about 180 ng / mL, about 185 ng / mL, about 190 ng / mL, about 195 ng / mL, about 200 ng / mL, about 205 ng / mL, about 210 ng / mL, about 215 ng / mL, about 220 ng / mL, about 225 ng / mL, about 230 ng / mL, about 235 ng / mL, or about 240 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fed conditions, wherein after administration the Cmaxof Compound 1 is about 25 ng / mL, about 30 ng / mL, about 35 ng / mL, about 40 ng / mL, about 45 ng / mL, about 50 ng / mL, about 55 ng / mL, about 60 ng / mL, about 65 ng / mL, about 70 ng / mL, about 75 ng / mL, about 80 ng / mL, about 85 ng / mL, about 90 ng / mL, about 95 ng / mL, about 100 ng / mL, about 105 ng / mL, about 110 ng / mL, about 115 ng / mL, about 120 ng / mL, about 125 ng / mL, about 130 ng / mL, about 135 ng / mL, about 140 ng / mL, about 145 ng / mL, about 150 ng / mL, about 155 ng / mL, about 160 ng / mL, about 165 ng / mL, about 170 ng / mL, about 175 ng / mL, about 180 ng / mL, about 185 ng / mL, about 190 ng / mL, about 195 ng / mL, about 200 ng / mL, about 205 ng / mL, about 210 ng / mL, about 215 ng / mL, about 220 ng / mL, about 225 ng / mL, about 230 ng / mL, about 235 ng / mL, or about 240 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 fasted conditions, wherein after administration the Cmax of Compound 1 is about 200 ng / mL, about 205 ng / mL, about 210 ng / mL, about 215 ng / mL, about 220 ng / mL, about 225 ng / mL, about 230 ng / mL, about 235 ng / mL, about 240 ng / mL, about 245 ng / mL, about 250 ng / mL, about 255 ng / mL, about 260 ng / mL, about 265 ng / mL, about 270 ng / mL, about 275 ng / mL, about 280 ng / mL, about 285 ng / mL, about 290 ng / mL, about 295 ng / mL, about 296 ng / mL, about 300 ng / mL, about 305 ng / mL, about 310 ng / mL, about 315 ng / mL, about 320 ng / mL, about 325 ng / mL, about 330 ng / mL, about 335 ng / mL, about 340 ng / mL, about 345 ng / mL, about 350 ng / mL, about 355 ng / mL, about 360 ng / mL, about 365 ng / mL, about 370 ng / mL, about 375 ng / mL, about 380 ng / mL, about 385 ng / mL, about 390 ng / mL, about 395 ng / mL, about 400 ng / mL, about 405 ng / mL, about 410 ng / mL, about 415 ng / mL, about 420 ng / mL, about 425 ng / mL, about 430 ng / mL, about 435 ng / mL, about 440 ng / mL, about 445 ng / mL, or about 450 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the Cmax of Compound 1 is about 180 ng / mL, about 185 ng / mL, about 190 ng / mL, about 195 ng / mL, about 200 ng / mL, about 205 ng / mL, about 210 ng / mL, about 215 ng / mL, about 220 ng / mL, about 225 ng / mL, about 230 ng / mL, about 235 ng / mL, about 240 ng / mL, about 245 ng / mL, about 250 ng / mL, about 255 ng / mL, about 260 ng / mL, about 265 ng / mL, about 270 ng / mL, about 275 ng / mL, about 280 ng / mL, about 285 ng / mL, about 290 ng / mL, about 295 ng / mL, about 296 ng / mL, about 300 ng / mL, about 305 ng / mL, about 310 ng / mL, about 315 ng / mL, about 320 ng / mL, about 325 ng / mL, about 330 ng / mL, about 335 ng / mL, about 340 ng / mL, about 345 ng / mL, about 350 ng / mL, about 355 ng / mL, about 360 ng / mL, about 365 ng / mL, about 370 ng / mL, about 375 ng / mL, about 380 ng / mL, about 385 ng / mL, about 390 ng / mL, about 395 ng / mL, about 400 ng / mL, about 405 ng / mL, about 410 ng / mL, about 415 ng / mL, about 420 ng / mL, about 425 ng / mL, about 430 ng / mL, about 435 ng / mL, about 440 ng / mL, about 445 ng / mL, about 450 ng / mL, about 455 ng / mL, about 460 ng / mL, about 465 ng / mL, or about 470 ng / mL.In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fasted conditions, wherein after administration the Cmaxof Compound 1 is about 305 ng / mL, 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 about 310 ng / mL, about 315 ng / mL, about 320 ng / mL, about 325 ng / mL, about 330 ng / mL, about 335 ng / mL, about 340 ng / mL, about 345 ng / mL, about 350 ng / mL, about 355 ng / mL, about 360 ng / mL, about 365 ng / mL, about 370 ng / mL, about 375 ng / mL, about 380 ng / mL, about 385 ng / mL, about 390 ng / mL, about 395 ng / mL, about 400 ng / mL, about 405 ng / mL, about 409 ng / mL, about 410 ng / mL, about 415 ng / mL, about 420 ng / mL, about 425 ng / mL, about 430 ng / mL, about 435 ng / mL, about 440 ng / mL, about 445 ng / mL, about 450 ng / mL, about 455 ng / mL, about 460 ng / mL, about 465 ng / mL, about 470 ng / mL, about 475 ng / mL, about 480 ng / mL, about 485 ng / mL, about 490 ng / mL, about 495 ng / mL, about 500 ng / mL, about 505 ng / mL, about 510 ng / mL, about 515 ng / mL, about 520 ng / mL, about 525 ng / mL, about 530 ng / mL, about 535 ng / mL, about 540 ng / mL, about 545 ng / mL, or about 550 ng / mL In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fed conditions, wherein after administration the Cmax of Compound 1 is about 160 ng / mL, about 165 ng / mL, about 170 ng / mL, about 175 ng / mL, about 180 ng / mL, about 185 ng / mL, about 190 ng / mL, about 195 ng / mL, about 200 ng / mL, about 205 ng / mL, about 210 ng / mL, about 215 ng / mL, about 220 ng / mL, about 225 ng / mL, about 230 ng / mL, about 235 ng / mL, about 240 ng / mL, about 245 ng / mL, about 250 ng / mL, about 255 ng / mL, about 260 ng / mL, about 265 ng / mL, about 270 ng / mL, about 275 ng / mL, about 280 ng / mL, about 285 ng / mL, about 290 ng / mL, about 295 ng / mL, about 300 ng / mL, about 305 ng / mL, about 310 ng / mL, about 315 ng / mL, about 320 ng / mL, about 325 ng / mL, about 330 ng / mL, about 335 ng / mL, about 340 ng / mL, about 345 ng / mL, about 350 ng / mL, about 355 ng / mL, about 360 ng / mL, about 365 ng / mL, about 370 ng / mL, about 375 ng / mL, about 380 ng / mL, about 385 ng / mL, about 390 ng / mL, about 395 ng / mL, about 400 ng / mL, about 405 ng / mL, about 410 ng / mL, about 415 ng / mL, or about 420 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the Cmax of Compound 1 is about 450 ng / mL, about 500 ng / mL, about 550 ng / mL, about 600 ng / mL, about 650 ng / mL, about 700 ng / mL, about 750 ng / mL, about 800 ng / mL, about 850 ng / mL, about 886 ng / mL, about 900 ng / mL, about 950 ng / mL, about 1,000 ng / mL, about 1,050 ng / mL, about 1,100 ng / mL, about 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 1,150 ng / mL, about 1,200 ng / mL, about 1,250 ng / mL, about 1,300 ng / mL, about 1,350 ng / mL, about 1,400 ng / mL, about 1,450 ng / mL, about 1,500 ng / mL, about 1,550 ng / mL, about 1,600 ng / mL, or about 1,650 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the Cmaxof Compound 1 is from about 350 ng / mL, about 400 ng / mL, about 450 ng / mL, about 500 ng / mL, about 550 ng / mL, about 600 ng / mL, about 650 ng / mL, about 700 ng / mL, about 750 ng / mL, about 800 ng / mL, about 850 ng / mL, about 886 ng / mL, about 900 ng / mL, about 950 ng / mL, about 1,000 ng / mL, about 1,050 ng / mL, about 1,100 ng / mL, about 1,150 ng / mL, about 1,200 ng / mL, about 1,250 ng / mL, about 1,300 ng / mL, about 1,350 ng / mL, about 1,400 ng / mL, about 1,450 ng / mL, about 1,500 ng / mL, about 1,550 ng / mL, about 1,600 ng / mL, about 1,650 ng / mL, about 1,700 ng / mL, about 1,750 ng / mL, about 1,800 ng / mL, or about 1,850 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the C24hof Compound 1 is from about 1 ng / mL to about 80 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the C24h of Compound 1 is from about 2 ng / mL to about 70 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the of Compound 1 is from about 3 ng / mL to about 60 ng / mL. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the C24hof Compound 1 is from about 4 ng / mL to about 50 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the C24h of Compound 1 is from about 5 ng / mL to about 40 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the C24h of Compound 1 is from about 6 ng / mL to about 30 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the C24hof Compound 1 is from about 1 ng / mL to about 60 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the C24h of Compound 1 is from about 1 ng / mL to about 50 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 fasted conditions, wherein after administration the C24h of Compound 1 is from about 1 ng / mL to about 40 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the C24hof Compound 1 is from about 1 ng / mL to about 30 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the C24h of Compound 1 is from about 1 ng / mL to about 20 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the C24hof Compound 1 is from about 1 ng / mL to about 10 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fed conditions, wherein after administration the C24hof Compound 1 is from about 1 ng / mL to about 80 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fed conditions, wherein after administration the C24h of Compound 1 is from about 2 ng / mL to about 70 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or 85 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fed conditions, wherein after administration the C24h of Compound 1 is from about 3 ng / mL to about 60 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fed conditions, wherein after administration the C24hof Compound 1 is from about 4 ng / mL to about 50 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fed conditions, wherein after administration the C24h of Compound 1 is from about 5 ng / mL to about 40 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fed conditions, wherein after administration the C24hof Compound 1 is from about 6 ng / mL to about 30 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fed conditions, wherein after administration the C24h of Compound 1 is from about 1 ng / mL to about 60 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fed conditions, wherein after administration the C24h of Compound 1 is from about 1 ng / mL to about 50 ng / mL. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fed conditions, wherein after administration the C24hof Compound 1 is from about 1 ng / mL to about 40 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fed conditions, wherein after administration the C24h of Compound 1 is from about 1 ng / mL to about 30 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fed conditions, wherein after administration the C24h of Compound 1 is from about 1 ng / mL to about 20 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fed conditions, wherein after administration the C24hof Compound 1 is from about 1 ng / mL to about 10 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the C24h of Compound 1 is from about 1 ng / mL to about 180 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 fasted conditions, wherein after administration the C24h of Compound 1 is from about 2 ng / mL to about 170 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the C24hof Compound 1 is from about 3 ng / mL to about 160 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the C24h of Compound 1 is from about 4 ng / mL to about 150 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the C24hof Compound 1 is from about 5 ng / mL to about 140 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the C24hof Compound 1 is from about 6 ng / mL to about 130 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the C24h of Compound 1 is from about 1 ng / mL to about 160 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or 88 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the C24h of Compound 1 is from about 1 ng / mL to about 140 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the C24hof Compound 1 is from about 1 ng / mL to about 120 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the C24h of Compound 1 is from about 1 ng / mL to about 100 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the C24hof Compound 1 is from about 1 ng / mL to about 80 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the C24h of Compound 1 is from about 1 ng / mL to about 60 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the C24h of Compound 1 is from about 1 ng / mL to about 180 ng / mL. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the C24hof Compound 1 is from about 2 ng / mL to about 170 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the C24h of Compound 1 is from about 3 ng / mL to about 160 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the C24h of Compound 1 is from about 4 ng / mL to about 150 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the C24hof Compound 1 is from about 5 ng / mL to about 140 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the C24h of Compound 1 is from about 6 ng / mL to about 130 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 fed conditions, wherein after administration the C24h of Compound 1 is from about 1 ng / mL to about 160 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the C24hof Compound 1 is from about 1 ng / mL to about 140 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the C24h of Compound 1 is from about 1 ng / mL to about 120 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the C24hof Compound 1 is from about 1 ng / mL to about 100 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the C24hof Compound 1 is from about 1 ng / mL to about 80 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the C24h of Compound 1 is from about 1 ng / mL to about 60 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or 91 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fasted conditions, wherein after administration the C24h of Compound 1 is from about 1 ng / mL to about 100 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fasted conditions, wherein after administration the C24hof Compound 1 is from about 5 ng / mL to about 80 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fasted conditions, wherein after administration the C24h of Compound 1 is from about 10 ng / mL to about 60 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fasted conditions, wherein after administration the C24hof Compound 1 is from about 15 ng / mL to about 40 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fed conditions, wherein after administration the C24h of Compound 1 is from about 1 ng / mL to about 100 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fed conditions, wherein after administration the C24h of Compound 1 is from about 5 ng / mL to about 80 ng / mL. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fed conditions, wherein after administration the C24hof Compound 1 is from about 10 ng / mL to about 60 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fed conditions, wherein after administration the C24h of Compound 1 is from about 15 ng / mL to about 40 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the C24h of Compound 1 is from about 1 ng / mL to about 180 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the C24hof Compound 1 is from about 5 ng / mL to about 170 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the C24h of Compound 1 is from about 10 ng / mL to about 160 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 at fasted conditions, wherein after administration the C24h of Compound 1 is from about 15 ng / mL to about 150 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the C24hof Compound 1 is from about 20 ng / mL to about 140 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the C24h of Compound 1 is from about 25 ng / mL to about 130 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the C24hof Compound 1 is from about 30 ng / mL to about 120 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the C24hof Compound 1 is from about 35 ng / mL to about 110 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the C24h of Compound 1 is from about 40 ng / mL to about 100 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or 94 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the C24h of Compound 1 is from about 45 ng / mL to about 90 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the C24hof Compound 1 is from about 50 ng / mL to about 80 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the C24h of Compound 1 is from about 55 ng / mL to about 70 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the C24hof Compound 1 is from about 1 ng / mL to about 180 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the C24h of Compound 1 is from about 5 ng / mL to about 170 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the C24h of Compound 1 is from about 10 ng / mL to about 160 ng / mL. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the C24hof Compound 1 is from about 15 ng / mL to about 150 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the C24h of Compound 1 is from about 20 ng / mL to about 140 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the C24h of Compound 1 is from about 25 ng / mL to about 130 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the C24hof Compound 1 is from about 30 ng / mL to about 120 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the C24h of Compound 1 is from about 35 ng / mL to about 110 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 at fed conditions, wherein after administration the C24h of Compound 1 is from about 40 ng / mL to about 100 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the C24hof Compound 1 is from about 45 ng / mL to about 90 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the C24h of Compound 1 is from about 50 ng / mL to about 80 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the C24hof Compound 1 is from about 55 ng / mL to about 70 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the C24hof Compound 1 is about 1 ng / mL, about 2 ng / mL, about 3 ng / mL, about 4 ng / mL, about 5 ng / mL, about 6 ng / mL, about 7 ng / mL, about 8 ng / mL, about 9 ng / mL, about 10 ng / mL, about 11 ng / mL, about 12 ng / mL, about 13 ng / mL, about 14 ng / mL, about 15 ng / mL, about 20 ng / mL, about 25 ng / mL, about 30 ng / mL, about 35 ng / mL, about 40 ng / mL, about 45 ng / mL, about 50 ng / mL, about 55 ng / mL, about 60 ng / mL, about 65 ng / mL, about 70 ng / mL, about 75 ng / mL, or about 80 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 20 mg at fed conditions, wherein after administration the C24h of Compound 1 is about 1 ng / mL, about 2 ng / mL, about 3 ng / mL, about 4 ng / mL, about 5 ng / mL, about 6 ng / mL, about 7 ng / mL, about 8 ng / mL, about 9 ng / mL, about 10 ng / mL, about 11 ng / mL, about 12 ng / mL, about 13 ng / mL, about 14 ng / mL, about 15 ng / mL, about 20 ng / mL, about 25 ng / mL, about 30 ng / mL, about 35 ng / mL, about 40 ng / mL, about 45 ng / mL, about 50 ng / mL, about 55 ng / mL, about 60 ng / mL, about 65 ng / mL, about 70 ng / mL, about 75 ng / mL, or about 80 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the C24h of Compound 1 is about 1 ng / mL, about 2 ng / mL, about 3 ng / mL, about 4 ng / mL, about 5 ng / mL, about 6 ng / mL, about 7 ng / mL, about 8 ng / mL, about 9 ng / mL, about 10 ng / mL, about 11 ng / mL, about 12 ng / mL, about 13 ng / mL, about 14 ng / mL, about 15 ng / mL, about 19 ng / mL, about 20 ng / mL, about 25 ng / mL, about 30 ng / mL, about 35 ng / mL, about 40 ng / mL, about 45 ng / mL, about 50 ng / mL, about 55 ng / mL, about 60 ng / mL, about 65 ng / mL, about 70 ng / mL, about 75 ng / mL, about 80 ng / mL, about 85 ng / mL, about 90 ng / mL, about 95 ng / mL, about 100 ng / mL, about 105 ng / mL, about 110 ng / mL, about 115 ng / mL, about 120 ng / mL, about 125 ng / mL, about 130 ng / mL, about 135 ng / mL, about 140 ng / mL, about 145 ng / mL, about 150 ng / mL, about 155 ng / mL, about 160 ng / mL, about 165 ng / mL, about 170 ng / mL, about 175 ng / mL, or about 180 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 40 mg at fed conditions, wherein after administration the C24h of Compound 1 is about 1 ng / mL, about 2 ng / mL, about 3 ng / mL, about 4 ng / mL, about 5 ng / mL, about 6 ng / mL, about 7 ng / mL, about 8 ng / mL, about 9 ng / mL, about 10 ng / mL, about 11 ng / mL, about 12 ng / mL, about 13 ng / mL, about 14 ng / mL, about 15 ng / mL, about 20 ng / mL, about 25 ng / mL, about 30 ng / mL, about 35 ng / mL, about 40 ng / mL, about 45 ng / mL, about 50 ng / mL, about 55 ng / mL, about 60 ng / mL, about 65 ng / mL, about 70 ng / mL, about 75 ng / mL, about 80 ng / mL, about 85 ng / mL, about 90 ng / mL, about 95 ng / mL, about 100 ng / mL, about 105 ng / mL, about 110 ng / mL, about 115 ng / mL, about 120 ng / mL, about 125 ng / mL, about 130 ng / mL, about 135 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 ng / mL, about 140 ng / mL, about 145 ng / mL, about 150 ng / mL, about 155 ng / mL, about 160 ng / mL, about 165 ng / mL, about 170 ng / mL, about 175 ng / mL, or about 180 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fasted conditions, wherein after administration the C24hof Compound 1 is about 1 ng / mL, about 2 ng / mL, about 3 ng / mL, about 4 ng / mL, about 5 ng / mL, about 6 ng / mL, about 7 ng / mL, about 8 ng / mL, about 9 ng / mL, about 10 ng / mL, about 11 ng / mL, about 12 ng / mL, about 13 ng / mL, about 14 ng / mL, about 15 ng / mL, about 18 ng / mL, about 20 ng / mL, about 25 ng / mL, about 30 ng / mL, about 35 ng / mL, about 40 ng / mL, about 45 ng / mL, about 50 ng / mL, about 55 ng / mL, about 60 ng / mL, about 65 ng / mL, about 70 ng / mL, about 75 ng / mL, about 80 ng / mL, about 85 ng / mL, about 90 ng / mL, about 95 ng / mL, or about 100 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 80 mg at fed conditions, wherein after administration the C24h of Compound 1 is about 1 ng / mL, about 2 ng / mL, about 3 ng / mL, about 4 ng / mL, about 5 ng / mL, about 6 ng / mL, about 7 ng / mL, about 8 ng / mL, about 9 ng / mL, about 10 ng / mL, about 11 ng / mL, about 12 ng / mL, about 13 ng / mL, about 14 ng / mL, about 15 ng / mL, about 20 ng / mL, about 22 ng / mL, about 25 ng / mL, about 30 ng / mL, about 35 ng / mL, about 40 ng / mL, about 45 ng / mL, about 50 ng / mL, about 55 ng / mL, about 60 ng / mL, about 65 ng / mL, about 70 ng / mL, about 75 ng / mL, about 80 ng / mL, about 85 ng / mL, about 90 ng / mL, about 95 ng / mL, or about 100 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the C24h of Compound 1 is about 1 ng / mL, about 2 ng / mL, about 3 ng / mL, about 4 ng / mL, about 5 ng / mL, about 6 ng / mL, about 7 ng / mL, about 8 ng / mL, about 9 ng / mL, about 10 ng / mL, about 11 ng / mL, about 12 ng / mL, about 13 ng / mL, about 14 ng / mL, about 15 ng / mL, about 20 ng / mL, about 25 ng / mL, about 30 ng / mL, about 35 ng / mL, about 40 ng / mL, about 45 ng / mL, about 50 ng / mL, about 55 ng / mL, about 59 ng / mL, about 60 ng / mL, about 65 ng / mL, about 70 ng / mL, about 75 ng / mL, 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 about 80 ng / mL, about 85 ng / mL, about 90 ng / mL, about 95 ng / mL, about 100 ng / mL, about 105 ng / mL, about 110 ng / mL, about 115 ng / mL, about 120 ng / mL, about 125 ng / mL, about 130 ng / mL, about 135 ng / mL, about 140 ng / mL, about 145 ng / mL, about 150 ng / mL, about 155 ng / mL, about 160 ng / mL, about 165 ng / mL, about 170 ng / mL, about 175 ng / mL, or about 180 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is orally administered at a daily dosage of about 160 mg at fed conditions, wherein after administration the C24hof Compound 1 is about 1 ng / mL, about 2 ng / mL, about 3 ng / mL, about 4 ng / mL, about 5 ng / mL, about 6 ng / mL, about 7 ng / mL, about 8 ng / mL, about 9 ng / mL, about 10 ng / mL, about 11 ng / mL, about 12 ng / mL, about 13 ng / mL, about 14 ng / mL, about 15 ng / mL, about 20 ng / mL, about 25 ng / mL, about 30 ng / mL, about 35 ng / mL, about 40 ng / mL, about 45 ng / mL, about 50 ng / mL, about 55 ng / mL, about 60 ng / mL, about 65 ng / mL, about 70 ng / mL, about 75 ng / mL, about 80 ng / mL, about 85 ng / mL, about 90 ng / mL, about 95 ng / mL, about 100 ng / mL, about 105 ng / mL, about 110 ng / mL, about 115 ng / mL, about 120 ng / mL, about 125 ng / mL, about 130 ng / mL, about 135 ng / mL, about 140 ng / mL, about 145 ng / mL, about 150 ng / mL, about 155 ng / mL, about 160 ng / mL, about 165 ng / mL, about 170 ng / mL, about 175 ng / mL, or about 180 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein administration of Compound 1 to the subject in a fed state results in reduced experienced adverse events when compared to administration of Compound 1 to the subject in a fasted state. In some embodiments, the present disclosure is directed to a method of inhibiting tyrosine kinase enzymatic activity of a protein selected from the group consisting of Abelson protein (ABL1), Abelson-related protein (ABL2), and a chimeric protein BCR-ABL1, comprising administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein administration of Compound 1 to the subject in a fed state results in reduced experienced adverse events when compared to administration of Compound 1 to the subject in a fasted state. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, the present disclosure is directed to a method of treating a disease, wherein modulation of BCR-ABL1 activity prevents, inhibits, or ameliorates the pathology and / or symptomology of the disease, in a patient, comprising administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein administration of Compound 1 to the subject in a fed state results in reduced experienced adverse events when compared to administration of Compound 1 to the subject in a fasted state. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises orally administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered to the subject at a daily dosage of about 20 mg, wherein the subject has not consumed calories for at least about 1 hour before or after the administration, and wherein after administration the AUCinf of Compound 1 is from about 500 ng*h / mL to about 600 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises orally administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered to the subject at a daily dosage of about 20 mg, wherein the subject consumed calories within about 1 hour of the administration, and wherein after administration the AUCinfof Compound 1 is from about 500 ng*h / mL to about 600 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises orally administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered to the subject at a daily dosage of about 40 mg, wherein the subject has not consumed calories for at least about 1 hour before or after the administration, and wherein after administration the AUCinf of Compound 1 is from about 2,000 ng*h / mL to about 2,200 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises orally administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered to the subject at a daily dosage of about 40 mg, wherein the subject consumed calories within about 1 hour of the administration, and 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 wherein after administration the AUCinf of Compound 1 is from about 2,000 ng*h / mL to about 2,200 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises orally administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered to the subject at a daily dosage of about 80 mg, wherein the subject has not consumed calories for at least about 1 hour before or after the administration, and wherein after administration the AUCinfof Compound 1 is from about 2,500 ng*h / mL to about 2,600 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises orally administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered to the subject at a daily dosage of about 80 mg, wherein the subject consumed calories within about 1 hour of the administration, and wherein after administration the AUCinf of Compound 1 is from about 2,200 ng*h / mL to about 2,300 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises orally administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered to the subject at a daily dosage of about 160 mg, wherein the subject has not consumed calories for at least about 1 hour before or after the administration, and wherein after administration the AUCinfof Compound 1 is from about 6,500 ng*h / mL to about 6,700 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises orally administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered to the subject at a daily dosage of about 160 mg, wherein the subject consumed calories within about 1 hour of the administration, and wherein after administration the AUCinf of Compound 1 is from about 6,500 ng*h / mL to about 6,700 ng*h / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises orally administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered to the subject at 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 a daily dosage of about 20 mg, wherein the subject has not consumed calories for at least about 1 hour before or after the administration, and wherein after administration the Cmax of Compound 1 is from about 70 ng / mL to about 150 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises orally administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered to the subject at a daily dosage of about 20 mg, wherein the subject consumed calories within about 1 hour of the administration, and wherein after administration the Cmaxof Compound 1 is from about 70 ng / mL to about 150 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises orally administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered to the subject at a daily dosage of about 40 mg, wherein the subject has not consumed calories for at least about 1 hour before or after the administration, and wherein after administration the Cmax of Compound 1 is from about 250 ng / mL to about 350 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises orally administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered to the subject at a daily dosage of about 40 mg, wherein the subject consumed calories within about 1 hour of the administration, and wherein after administration the Cmaxof Compound 1 is from about 250 ng / mL to about 350 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises orally administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered to the subject at a daily dosage of about 80 mg, wherein the subject has not consumed calories for at least about 1 hour before or after the administration, and wherein after administration the Cmax of Compound 1 is from about 350 ng / mL to about 460 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises orally administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition 103 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 comprising Compound 1, wherein Compound 1 is administered to the subject at a daily dosage of about 80 mg, wherein the subject consumed calories within about 1 hour of the administration, and wherein after administration the Cmax of Compound 1 is from about 200 ng / mL to about 330 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises orally administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered to the subject at a daily dosage of about 160 mg, wherein the subject has not consumed calories for at least about 1 hour before or after the administration, and wherein after administration the Cmaxof Compound 1 is from about 800 ng / mL to about 950 ng / mL. In some embodiments, the method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises orally administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered to the subject at a daily dosage of about 160 mg, wherein the subject consumed calories within about 1 hour of the administration, and wherein after administration the Cmax of Compound 1 is from about 800 ng / mL to about 950 ng / mL. In some embodiments, the present disclosure is directed to a method of inhibiting tyrosine kinase enzymatic activity of a protein selected from the group consisting of Abelson protein (ABL1), Abelson-related protein (ABL2), and a chimeric protein BCR-ABL1, comprising administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered at a daily dosage of between about 5 mg and about 700 mg, and wherein the difference between AUCinfof Compound 1 if administered under fed conditions and AUCinfof Compound 1 if administered under fasted conditions is less than about 40%. In some embodiments, the present disclosure is directed to a method of treating a disease, wherein modulation of BCR-ABL1 activity prevents, inhibits, or ameliorates the pathology and / or symptomology of the disease, in a patient, comprising administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered at a daily dosage of between about 5 mg and about 700 mg, and wherein the difference between AUCinf of Compound 1 if administered under fed conditions and AUCinf of Compound 1 if administered under fasted conditions is less than about 40%. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, the present disclosure is directed to a method of treating leukemia in a patient comprising administering to the patient a therapeutically effective amount of Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein the leukemia is chronic myeloid leukemia (CML), acute myeloid leukemia (AML), or acute lymphoblastic leukemia (ALL). In some embodiments, the AML is secondary AML, which develops after myelodysplastic syndromes (MDS) or myeloproliferative neo-plasms (MPN). In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered twice daily. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once daily, for example, at any of the dosage described herein. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once daily, for example, at any of the dosage described herein, under fasted conditions. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once daily, for example, at any of the dosage described herein, under fed conditions. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered under fasted or fed conditions once daily, for example, at any of the dosage described herein, for one day per week. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered under fasted or fed conditions once daily, for example, at any of the dosage described herein, for two days per week. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered under fasted or fed conditions once daily, for example, at any of the dosage described herein, for three days per week. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered under fasted or 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 fed conditions once daily, for example, at any of the dosage described herein, for four days per week. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered under fasted or fed conditions once daily, for example, at any of the dosage described herein, for five days per week. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered under fasted or fed conditions once daily, for example, at any of the dosage described herein, for six days per week. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered under fasted or fed conditions once daily, for example, at any of the dosage described herein, for seven days per week. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered under fasted or fed conditions once daily, for example, at any of the dosage described herein, for two weeks. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered under fasted or fed conditions once daily, for example, at any of the dosage described herein, for three weeks. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered under fasted or fed conditions once daily, for example, at any of the dosage described herein, for four weeks. In some embodiment, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered under fasted or fed conditions, for example, at any of the dosage described herein, without a dosing holiday. In some embodiment, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered under fasted or fed conditions, for example, at any of the dosage described herein, followed by a dosing holiday. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once a day continuously. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered twice a day continuously. In some embodiments, Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered orally. Also included is Compound 1, both in the pharmaceutically acceptable salt form and in the neutral form. In some embodiments, the method comprises administering Compound 1, wherein Compound 1 is rapidly absorbed. In some embodiments, the method comprises administering Compound 1, such that Compound 1 has median Tmax occurring 1.5 to 2.3 hours post dose. In some embodiments, the method comprises administering Compound 1, such that median half-life from 8 to 14 hours. In some embodiments, administering Compound 1 at various doses results in approximately linear increases in AUC from 20 to 400 mg. In some embodiments, administering Compound 1 at various doses results in approximately linear increases in Cmax from 20 to 320 mg. In some embodiments, the method comprises administering Compound 1, such that when Compound 1 is administered with a high-fat meal, Compound 1 AUCinf is between 85% and 95% of the fasted state AUCinf. In some embodiments, the method comprises administering Compound 1, such that when Compound 1 is administered with a high-fat meal, Compound 1 Cmax is between 55% and 70% of the fasted state Cmax. Articles of Manufacture and Kits The present disclosure further provides articles of manufacture comprising Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 described herein, or one or more unit dosages described herein in suitable packaging. In certain embodiments, the article of manufacture is for use in any of the methods described herein. Suitable packaging is known in the art and includes, for example, vials, vessels, ampules, bottles, jars, flexible packaging and the like. An article of manufacture may further be sterilized and / or sealed. The present disclosure further provides kits for carrying out the methods of the present disclosure, which comprises Compound 1, or the pharmaceutically acceptable salt 107 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 thereof, or the pharmaceutical composition comprising Compound 1. The kits may employ Compound 1. In one variation, the kit employs Compound 1 or a salt thereof. The kits may be used for any one or more of the uses described herein, and, accordingly, may contain instructions for the treatment of any disease or described herein, for example for the treatment of cancer. The kits may be in unit dosage forms, bulk packages (e.g., multi-dose packages) or sub-unit doses. For example, kits may be provided that contain sufficient dosages of Compound 1 and / or an additional pharmaceutically active compound useful for a disease detailed herein to provide effective treatment of a patient for an extended period, such as any of a week, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 3 months, 4 months, 5 months, 7 months, 8 months, 9 months, or more. Kits may also include multiple unit doses of Compound 1 and instructions for use and be packaged in quantities sufficient for storage and use in pharmacies (e.g., hospital pharmacies and compounding pharmacies). The kits may optionally include a set of instructions, generally written instructions, although electronic storage media (e.g., magnetic diskette or optical disk) containing instructions are also acceptable, relating to the use of component(s) of the methods of the present disclosure. The instructions included with the kit generally include information as to the components and their administration to a patient. In some embodiments, the present disclosure is directed to a kit comprising Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, and printed instructions for using Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 in a subject for the treatment for leukemia. Exemplary Embodiments The present disclosure is further described by the following embodiments. The features of each of the embodiments are combinable with any of the other embodiments where appropriate and practical. Embodiment 1. A method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprising administering to the subject Compound 1: 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 (Compound 1), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered to a fed subject at a daily dosage of between about 5 mg and about 700 mg, and wherein the difference between AUCinf of Compound 1 if administered under fed conditions and AUCinf of Compound 1 if administered under fasted conditions is less than about 40%. Embodiment 2. The method of embodiment 1, wherein the difference between AUCinf of Compound 1 if administered under fed conditions and AUCinf of Compound 1 if administered under fasted conditions is less than about 35%. Embodiment 3. The method of embodiment 1, wherein the difference between AUCinf of Compound 1 if administered under fed conditions and AUCinf of Compound 1 if administered under fasted conditions is less than about 30%. Embodiment 4. The method of embodiment 1, wherein the difference between AUCinf of Compound 1 if administered under fed conditions and AUCinf of Compound 1 if administered under fasted conditions is less than about 25%. Embodiment 5. The method of embodiment 1, wherein the difference between AUCinf of Compound 1 if administered under fed conditions and AUCinf of Compound 1 if administered under fasted conditions is less than about 20%. Embodiment 6. The method of embodiment 1, wherein the difference between AUCinf of Compound 1 if administered under fed conditions and AUCinf of Compound 1 if administered under fasted conditions is less than about 15%. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 Embodiment 7. A method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1 (Compound 1), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered to a fed subject at a daily dosage of between about 5 mg and about 700 mg, and wherein the difference between Cmax of Compound 1 if administered under fed conditions and Cmax of Compound 1 if administered under fasted conditions is less than about 60%. Embodiment 8. The method of embodiment 7, wherein the difference between Cmax of Compound 1 if administered under fed conditions and Cmax of Compound 1 if administered under fasted conditions is less than about 55%. Embodiment 9. The method of embodiment 7, wherein the difference between Cmax of Compound 1 if administered under fed conditions and Cmax of Compound 1 if administered under fasted conditions is less than about 50%. Embodiment 10. The method of embodiment 7, wherein the difference between Cmax of Compound 1 if administered under fed conditions and Cmax of Compound 1 if administered under fasted conditions is less than about 45%. Embodiment 11. The method of embodiment 7, wherein the difference between Cmax of Compound 1 if administered under fed conditions and Cmax of Compound 1 if administered under fasted conditions is less than about 40%. Embodiment 12. The method of any one of the preceding embodiments, wherein Compound 1, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once daily. Embodiment 13. The method of any one of the preceding embodiments, wherein Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered orally. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 Embodiment 14. The method of any one of the preceding embodiments, wherein Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a daily dosage of about 20 mg. Embodiment 15. The method of any one of the preceding embodiments, wherein Compound 1, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a daily dosage of about 40 mg. Embodiment 16. The method of any one of the preceding embodiments, wherein Compound 1, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a daily dosage of about 80 mg. Embodiment 17. The method of any one of the preceding embodiments, wherein Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a daily dosage of about 160 mg. Embodiment 18. The method of any one of the preceding embodiments, wherein Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a daily dosage of about 320 mg. Embodiment 19. The method of any one of the preceding embodiments, wherein Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a daily dosage of about 400 mg. Embodiment 20. The method of any one of the preceding embodiments, wherein the cancer is a leukemia. Embodiment 21. The method of any one of the preceding embodiments, wherein Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered with food. Embodiment 22. The method of any one of the preceding embodiments, wherein Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered without food. Embodiment 23. The method of any one of the preceding embodiments, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the AUCinf of Compound 1 is from about 500 ng*h / mL to about 600 ng*h / mL. Embodiment 24. The method of any one of the preceding embodiments, wherein Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, is orally administered at a daily dosage of about 40 mg 111 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 at fasted conditions, wherein after administration the AUCinf of Compound 1 is from about 2,000 ng*h / mL to about 2,200 ng*h / mL. Embodiment 25. The method of any one of the preceding embodiments, wherein Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, is orally administered at a daily dosage of about 80 mg at fasted conditions, wherein after administration the AUCinf of Compound 1 is from about 2,500 ng*h / mL to about 2,600 ng*h / mL. Embodiment 26. The method of any one of the preceding embodiments, wherein Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, is orally administered at a daily dosage of about 80 mg at fed conditions, wherein after administration the AUCinf of Compound 1 is from about 2,200 ng*h / mL to about 2,300 ng*h / mL. Embodiment 27. The method of any one of the preceding embodiments, wherein Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the AUCinf of Compound 1 is from about 6,500 ng*h / mL to about 6,700 ng*h / mL. Embodiment 28. The method of any one of the preceding embodiments, herein Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, is orally administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the Cmax of Compound 1 is from about 70 ng / mL to about 150 ng / mL. Embodiment 29. The method of any one of the preceding embodiments, wherein Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, is orally administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the Cmax of Compound 1 is from about 250 ng / mL to about 350 ng / mL. Embodiment 30. The method of any one of the preceding embodiments, wherein Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, is orally administered at a daily dosage of about 80 mg at fasted conditions, wherein after administration the Cmax of Compound 1 is from about 350 ng / mL to about 460 ng / mL. 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 Embodiment 31. The method of any one of the preceding embodiments, wherein Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, is orally administered at a daily dosage of about 80 mg at fed conditions, wherein after administration the Cmax of Compound 1 is from about 200 ng / mL to about 330 ng / mL. Embodiment 32. The method of any one of the preceding embodiments, wherein Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the Cmax of Compound 1 is from about 800 ng / mL to about 950 ng / mL. Embodiment 33. A method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1: (Compound 1), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the C24h of Compound 1 is from about 1 ng / mL to about 80 ng / mL. Embodiment 34. A method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1: (Compound 1), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered at a daily dosage of about 40 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 mg at fasted conditions, wherein after administration the C24h of Compound 1 is from about 1 ng / mL to about 180 ng / mL. Embodiment 35. A method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1: (Compound 1), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered at a daily dosage of about 80 mg at fasted conditions, wherein after administration the C24h of Compound 1 is from about 1 ng / mL to about 100 ng / mL. Embodiment 36. A method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1: (Compound 1), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered at a daily dosage of about 80 mg at fed conditions, wherein after administration the C24h of Compound 1 is from about 1 ng / mL to about 100 ng / mL. Embodiment 37. A method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1: 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 (Compound 1), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the C24h of Compound 1 is from about 1 ng / mL to about 180 ng / mL. Embodiment 38. A method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein administration of Compound 1 to the subject in a fed state results in reduced experienced adverse events when compared to administration of Compound 1, or another BCR-ABL1 inhibitor, to the subject in a fasted state. Embodiment 39. A method of inhibiting tyrosine kinase enzymatic activity of a protein selected from the group consisting of Abelson protein (ABL1), Abelson-related protein (ABL2), and a chimeric protein BCR-ABL1, comprising administering to the subject Compound 1: (Compound 1), or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein administration of Compound 1 to the subject in a fed state results in reduced experienced adverse events when compared to administration of Compound 1 to the subject in a fasted state. Embodiment 40. A method of treating a disease, wherein modulation of BCR- ABL1 activity prevents, inhibits, or ameliorates the pathology and / or symptomology of the disease, in a patient, comprising administering to the subject Compound 1: 317610242 Attorney Docket No.: TRPH-054 / 001WO 346923-2814 (Compound 1), or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein administration of Compound 1 to the subject in a fed state results in reduced experienced adverse events when compared to administration of Compound 1 to the subject in a fasted state. Embodiment 41. A kit comprising Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, and printed instructions for using Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 in a subject for the treatment for leukemia. Embodiment 42. A method of inhibiting tyrosine kinase enzymatic activity of a protein selected from the group consisting of Abelson protein (ABL1), Abelson-related protein (ABL2), and a chimeric protein BCR-ABL1, comprising administering to the subject Compound 1: (Compound 1), or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, wherein Compound 1 is administered at a daily dosage of between about 5 mg and about 700 mg, and wherein the difference between AUCinf of Compound 1 if administ...

Claims

Attorney Docket No.: TRPH-054 / 001WO 346923-2814 CLAIMS What is claimed is:

1. A method of treating a leukemia in a subject in need thereof, comprising administering to the subject Compound 1:(Compound 1), or a pharmaceutically acceptable salt thereof, or a tautomer of Compound 1 or a pharmaceutically acceptable salt thereof, or a prodrug thereof, or a pharmaceutical composition comprising any of the foregoing, wherein Compound 1 is administered to a fed subject at a daily dosage of between about 5 mg and about 700 mg, and wherein the difference between AUCinf of Compound 1 if administered under fed conditions and AUCinf of Compound 1 if administered under fasted conditions is less than about 40%.

2. The method of claim 1, wherein the difference between AUCinf of Compound 1 if administered under fed conditions and AUCinf of Compound 1 if administered under fasted conditions is less than about 35%, less than about 30%, less than about 25%, less than about 20%, and / or less than about 15%.

3. A method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1:(Compound 1), or a pharmaceutically acceptable salt thereof, or a tautomer of Compound 1 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising any of the foregoing, wherein Compound 1 is administered to a fed subject at a daily dosage of 317610242Attorney Docket No.: TRPH-054 / 001WO 346923-2814 between about 5 mg and about 700 mg, and wherein the difference between Cmax of Compound 1 if administered under fed conditions and Cmax of Compound 1 if administered under fasted conditions is less than about 60%.

4. The method of claim 3, wherein the difference between Cmaxof Compound 1 if administered under fed conditions andof Compound 1 if administered under fasted conditions is less than about 55%, less than about 50%, less than about 45%, and / or less than about 40%.

5. The method of any one of the preceding claims, wherein Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered once daily.

6. The method of any one of the preceding claims, wherein Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered orally.

7. The method of any one of the preceding claims, wherein Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a daily dosage of about 80 mg.

8. The method of any one of the preceding claims, wherein Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a daily dosage of about 160 mg.

9. The method of any one of the preceding claims, wherein Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a daily dosage of about 320 mg.

10. The method of any one of the preceding claims, wherein Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a daily dosage of about 400 mg. 317610242Attorney Docket No.: TRPH-054 / 001WO 346923-2814 11. The method of any one of the preceding claims, wherein Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered at a daily dosage of about 500 mg.

12. The method of any one of the preceding claims, wherein the cancer is a leukemia.

13. The method of any one of the preceding claims, wherein Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered with food.

14. The method of any one of the preceding claims, wherein Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1 is administered without food.

15. The method of any one of the preceding claims, wherein Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the AUCinf of Compound 1 is from about 6,500 ng*h / mL to about 6,700 ng*h / mL.

16. The method of any one of the preceding claims, wherein Compound 1, or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition comprising Compound 1, is orally administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the Cmaxof Compound 1 is from about 800 ng / mL to about 950 ng / mL.

17. A method of treating, preventing, or reducing the severity of a cancer in a subject in need thereof, comprises administering to the subject Compound 1: 317610242Attorney Docket No.: TRPH-054 / 001WO 346923-2814(Compound 1), or a pharmaceutically acceptable salt thereof, or a tautomer of Compound 1 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising any of the foregoing, wherein Compound 1 is administered at a daily dosage of about 20 mg at fasted conditions, wherein after administration the C24hof Compound 1 is from about 1 ng / mL to about 80 ng / mL.

18. A method of treating a cancer in a subject in need thereof, comprises administering to the subject Compound 1:(Compound 1), or a pharmaceutically acceptable salt thereof, or a tautomer of Compound 1 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising any of the foregoing, wherein Compound 1 is administered at a daily dosage of about 40 mg at fasted conditions, wherein after administration the C24hof Compound 1 is from about 1 ng / mL to about 180 ng / mL.

19. A method of treating a cancer in a subject in need thereof, comprises administering to the subject Compound 1: 317610242Attorney Docket No.: TRPH-054 / 001WO 346923-2814(Compound 1), or a pharmaceutically acceptable salt thereof, or a tautomer of Compound 1, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising any of the foregoing, wherein Compound 1 is administered at a daily dosage of about 80 mg at fasted conditions, wherein after administration the C24hof Compound 1 is from about 1 ng / mL to about 100 ng / mL.

20. A method of treating a cancer in a subject in need thereof, comprises administering to the subject Compound 1:(Compound 1), or a pharmaceutically acceptable salt thereof, or a tautomer of Compound 1 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising any of the foregoing, wherein Compound 1 is administered at a daily dosage of about 80 mg at fed conditions, wherein after administration the C24hof Compound 1 is from about 1 ng / mL to about 100 ng / mL.

21. A method of treating a cancer in a subject in need thereof, comprises administering to the subject Compound 1: 317610242Attorney Docket No.: TRPH-054 / 001WO 346923-2814(Compound 1), or a pharmaceutically acceptable salt thereof, or a tautomer of Compound 1 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising any of the foregoing, wherein Compound 1 is administered at a daily dosage of about 160 mg at fasted conditions, wherein after administration the C24hof Compound 1 is from about 1 ng / mL to about 180 ng / mL.

22. A method of treating a cancer in a subject in need thereof, comprises administering to the subject Compound 1, or a pharmaceutically acceptable salt thereof, or a tautomer of Compound 1 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising any of the foregoing, wherein administration of Compound 1 to the subject in a fed state results in reduced experienced adverse events when compared to administration of Compound 1, or another BCR-ABL1 inhibitor, to the subject in a fasted state.

23. A method of inhibiting tyrosine kinase enzymatic activity of a protein selected from the group consisting of Abelson protein (ABL1), Abelson-related protein (ABL2), and a chimeric protein BCR-ABL1, comprising administering to the subject Compound 1:(Compound 1), or a pharmaceutically acceptable salt thereof, or a tautomer of Compound 1 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising any of the foregoing, wherein administration of Compound 1 to the subject in a fed state results in reduced experienced adverse events when compared to administration of Compound 1 to the subject in a fasted state. 317610242Attorney Docket No.: TRPH-054 / 001WO 346923-2814 24. A method of treating a disease, wherein modulation of BCR-ABL1 activity prevents, inhibits, or ameliorates the pathology and / or symptomology of the disease, in a patient, comprising administering to the subject Compound 1:(Compound 1), or a pharmaceutically acceptable salt thereof, or a tautomer of Compound 1 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising any of the foregoing, wherein administration of Compound 1 to the subject in a fed state results in reduced experienced adverse events when compared to administration of Compound 1 to the subject in a fasted state.

25. A kit comprising Compound 1, or a pharmaceutically acceptable salt thereof, or a tautomer of Compound 1 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising any of the foregoing, and printed instructions for using Compound 1, or a pharmaceutically acceptable salt thereof, or a tautomer of Compound 1 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising any of the foregoing, in a subject for the treatment for leukemia, wherein the instructions provide for the administration of Compound 1 in a fed or fasted state.

26. A method of inhibiting tyrosine kinase enzymatic activity of a protein selected from the group consisting of Abelson protein (ABL1), Abelson-related protein (ABL2), and a chimeric protein BCR-ABL1, comprising administering to the subject Compound 1:317610242Attorney Docket No.: TRPH-054 / 001WO 346923-2814 or a pharmaceutically acceptable salt thereof, or a tautomer of Compound 1 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising any of the foregoing, wherein Compound 1 is administered at a daily dosage of between about 5 mg and about 700 mg, and wherein the difference between AUCinfof Compound 1 if administered under fed conditions and AUCinfof Compound 1 if administered under fasted conditions is less than about 40%.

27. A method of treating a disease, wherein modulation of BCR-ABL1 activity prevents, inhibits, or ameliorates the pathology and / or symptomology of the disease, in a patient, comprising administering to the subject Compound 1:(Compound 1), or a pharmaceutically acceptable salt thereof, or a tautomer of Compound 1 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising any of the foregoing, wherein Compound 1 is administered at a daily dosage of between about 5 mg and about 700 mg, and wherein the difference between AUCinf of Compound 1 if administered under fed conditions and AUCinfof Compound 1 if administered under fasted conditions is less than about 40%.

28. A method of treating leukemia in a patient comprising administering to the patient a therapeutically effective amount of Compound 1:(Compound 1), or a pharmaceutically acceptable salt thereof, or a tautomer of Compound 1 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising any of 317610242Attorney Docket No.: TRPH-054 / 001WO 346923-2814 the foregoing, wherein the leukemia is chronic myeloid leukemia (CML), acute myeloid leukemia (AML), or acute lymphoblastic leukemia (ALL), wherein the patient consumed food within three hours, within two hours, or within one hour of administration.

29. The method of any one of the preceding claims, wherein Compound 1 is a pharmaceutically acceptable salt or tautomer thereof.

30. The method of any one of the preceding claims, wherein administering Compound 1 comprises providing a subject with a pharmaceutical composition comprisingpharmaceutically acceptable salt thereof.

31. The method of any one of the preceding claims, wherein the cancer is leukemia.

32. The method of claim 31, wherein the leukemia is chronic myeloid leukemia (CML), acute myeloid leukemia (AML), or acute lymphoblastic leukemia (ALL). 317610242

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