Pharmaceutical compositions comprising combinations of elaraglusib and other therapeutic agents for the treatment of cancer

Abstract

Provided herein are compositions and methods for the treatment of cancer and related diseases and conditions. In particular, the present disclosure provides compositions and methods for the use of a pharmaceutical composition in combination with one or more anticancer therapies or agents.

Description

PHARMACEUTICAL COMPOSITIONS COMPRISING COMBINATIONS OF ELARAGLUSIB AND OTHER THERAPEUTIC AGENTS FOR THE TREATMENT OF CANCERRELATED APPLICATION INFORMATION

[0001] This application claims priority to U.S. Application No. 63 / 733,535 filed on December 13, 2024, the contents of which are herein incorporated by reference.FIELD

[0002] The present disclosure relates to pharmaceutical compositions and methods of treating cancer. In particular, the present disclosure provides pharmaceutical compositions containing elraglusib in combination with at least one other active agent and the use of these composition to treat cancer.BACKGROUND

[0003] Difficult-to-treat cancers, such as pancreatic cancer, malignant bone tumors, soft tissue malignant tumors, brain cancer, and acute myeloid leukemia (AML), remain some of the most challenging diseases in oncology due to their aggressive progression, resistance to conventional therapies, and often poor prognosis. Together, these cancers impact hundreds of thousands of individuals worldwide each year, substantially reducing life expectancy and quality of life for patients and their families. For instance, pancreatic cancer alone affects over 60,000 people annually in the United States, with a five-year survival rate of less than 10% due to late-stage diagnoses and limited treatment effectiveness. Similarly, brain cancers, including aggressive forms like glioblastoma, present a five-year survival rate of only 5-10% and claim thousands of lives each year, hindered by limited therapeutic options and a high tendency to recur despite treatment.

[0004] Malignant bone and soft tissue tumors affect both children and adults, posing unique challenges as they often resist chemotherapy and radiotherapy, leaving surgical resection as the primary treatment option. AML, which predominantly affects older adults, exhibits survival rates that decline with age; while the five-year survival rate for patients under twenty years of age may reach around 65%, and drops significantly in older populations due to the disease’s aggressive nature and patients' reduced tolerance for intensive chemotherapy.

[0005] The high incidence, low survival rates, and limited effectiveness of existing treatments for these cancers underscore the need for innovative approaches targeting their unique biologicalmechanisms. Standard treatment approaches — surgery, radiation, and chemotherapy — remain essential in managing these cancers; however, they frequently prove inadequate, especially in advanced or recurrent cases. Pancreatic cancer, for instance, is known for evading early detection and quickly developing resistance to chemotherapy. Malignant bone and soft tissue tumors often recur despite aggressive surgical and radiation interventions, while brain cancers face the additional obstacle of the blood-brain barrier, which restricts drug delivery. Additionally, AML progresses rapidly and frequently relapses following initial chemotherapy.

[0006] These challenges are largely driven by the cancers’ capacity for genetic mutations, altered signaling pathways, and immune evasion, which allow them to survive and adapt despite conventional treatments. Consequently, there is an urgent need for innovative therapies that can precisely target the molecular drivers of these cancers while working synergistically with existing treatments to enhance efficacy. Advanced therapeutic approaches designed to counteract resistance mechanisms, when used in combination with current anticancer agents, offer promising potential to significantly improve patient outcomes for these hard-to-treat cancers.SUMMARY

[0007] The present disclosure relates to pharmaceutical compositions and methods for the treatment of cancer and related diseases and conditions. In some aspects, the pharmaceutical compositions comprise: a combination of a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of: (a) oxaliplatin + liposomal irinotecan + 5-FU + leucovorin (NALIRIFOX); (b) oxaliplatin + irinotecan + 5-FU + leucovorin (FOLFIRINOX); (c) ifosfamide; (d) ifosfamide and topotecan; (e) cyclophosphamide and topotecan; (f) carmustine; (g) procarbazine; (h) cytarabine; (i) cytarabine and daunorubicin; (j) gemcitabine and cisplatin; (k) gemcitabine, cisplatin at least one PART inhibitor; and (1) at least one FLT3 inhibitor; wherein the combination is formulated for simultaneous, sequential, and / or separate administration, and for is suitable for oral administration, intrathecal administration and / or intravenous administration subject. In some aspects, the pharmaceutical composition is a single pharmaceutical composition (e.g., a single dosage form). In another aspect, the pharmaceutical composition comprises two pharmaceutical compositions (e.g., two dosage forms). In still another aspect, the pharmaceutical composition comprises three pharmaceutical compositions (e.g., three dosage forms). In still another aspect, the pharmaceutical composition comprises four pharmaceutical compositions (e.g., four dosage forms). In still another aspect, thepharmaceutical composition comprises five pharmaceutical compositions (e.g., five dosage forms). In still another aspect, the pharmaceutical composition comprises six pharmaceutical compositions (e.g., six dosage forms). In still another aspect, the pharmaceutical composition comprises seven pharmaceutical compositions (e.g., seven dosage forms). In still another aspect, the pharmaceutical composition comprises eight pharmaceutical compositions (e.g., eight dosage forms). In still another aspect, the pharmaceutical composition comprises nine pharmaceutical compositions (e.g., nine dosage forms). In still another aspect, the pharmaceutical composition comprises ten pharmaceutical compositions (e.g., ten dosage forms).

[0008] In some aspects, the pharmaceutical composition(s) is suitable for oral administration.

[0009] In some aspects, the pharmaceutical composition(s) is a solid dosage form.

[0010] In certain aspects, the solid dosage form is a capsule or tablet.

[0011] In some aspects, the pharmaceutical composition(s) is suitable for intravenous injection.

[0012] In some aspects, the pharmaceutical composition(s) is suitable for intrathecal injection.

[0013] In some aspects, the pharmaceutical composition(s) comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of NALIRIFOX.

[0014] In some aspects, the pharmaceutical composition(s) comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of FOLFIRINOX.

[0015] In some aspects, the pharmaceutical composition(s) comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of ifosfamide.

[0016] In some aspects, the pharmaceutical composition(s) comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof, a therapeutically effective amount of ifosfamide and a therapeutically effective amount of topotecan.

[0017] In some aspects, the pharmaceutical composition(s) comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of cyclophosphamide and a therapeutically effective amount of topotecan.

[0018] In some aspects, the pharmaceutical composition(s) comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of carmustine.

[0019] In some aspects, the pharmaceutical composition(s) comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of procarbazine.

[0020] In some aspects, the pharmaceutical composition(s) comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of cytarabine.

[0021] In some aspects, the pharmaceutical composition(s) comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of cytarabine and a therapeutically effective amount of daunorubicin.

[0022] In some aspects, the pharmaceutical composition(s) comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of gemcitabine and a therapeutically effective amount of cisplatin.

[0023] In some aspects, the pharmaceutical composition(s) comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of gemcitabine, a therapeutically effective amount of cisplatin, and a therapeutically effective amount at least one PARP inhibitor. In some aspects, the at least one PARP inhibitor is olaparib, talazoparib, rucaparib, niraparib or any combination thereof.

[0024] In some aspects, the pharmaceutical composition(s) comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of at least one FLT3 inhibitor. In some aspects, the at least one FLT3 inhibitor is gilteritinib, midostaurin, quizartinib, or any combination thereof.

[0025] In some aspects, the therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof is from about 5 mg / kg to about 50 mg / kg.

[0026] In some aspects, the therapeutically effective amount of NALIRIFOX * oxaliplatin + liposomal irinotecan + 5-FU + leucovorin) is from about 40 mg / m2to about 2400 mg / m2.

[0027] In some aspects, the therapeutically effective amount of FOLFIRINOX (oxaliplatin + irinotecan + 5-FU + leucovorin) is from about 40 mg / m2to about 2400 mg / m2.

[0028] In some aspects, the therapeutically effective amount of ifosfamide is from about 0.5 g / m2to about 5 g / m2.

[0029] In some aspects, the therapeutically effective amount of cyclophosphamide is from about from about 1 mg / kg to about 75 mg / kg.

[0030] In some aspects, the therapeutically effective amount of topotecan is from about from about 0.5 mg / m2to about 3 mg / m2.

[0031] In some aspects, the therapeutically effective amount of carmustine is from about from about 50 mg / m2to about 1 g / m2.

[0032] In some aspects, the therapeutically effective amount of procarbazine is from about 1 mg / kg to about 10 mg / kg.

[0033] In some aspects, the therapeutically effective amount of cytarabine is from about 1 mg / m2to about 5 g / m2.

[0034] In some aspects, the therapeutically effective amount of daunorubicin is from about 40 mg / m2to about 900 mg / m2.

[0035] In some aspects, the therapeutically effective amount of olaparib is from about 300 mg to about 600 mg.

[0036] In some aspects, the therapeutically effective amount of talazoparib is from about 0.1 mg to about 2 mg.

[0037] In some aspects, the therapeutically effective amount of rucaparib is from about 200 mg to about 600 mg.

[0038] In some aspects, the therapeutically effective amount of niraparib is from about 200 mg to about 400 mg.

[0039] In some aspects, the therapeutically effective amount of gilteritinib is from about 20 mg to about 150 mg.

[0040] In some aspects, the therapeutically effective amount of midostaurin is from about 50 mg to about 250 mg.

[0041] In some aspects, the therapeutically effective amount of quizartinib is from about 25 mg to about 100 mg.

[0042] In some aspects, the pharmaceutical composition(s) further comprises one or more pharmaceutically acceptable excipients.

[0043] In some aspects, the present disclosure provides a method of treating a subject suffering from cancer, the method comprising the step of administering to a subject suffering from cancer one or more of the above described pharmaceutical compositions.

[0044] In some aspects of the above method, the cancer is pancreatic cancer, malignant bone tumors, soft tissue malignant tumors, brain cancer, acute myeloid leukemia (AML) or any combinations thereof.

[0045] In some aspects of the above method, the malignant bone tumor is osteosarcoma, Ewing sarcoma, chondrosarcoma, or combinations thereof.

[0046] In some aspects of the above method, the soft tissue malignant tumor is liposarcoma, leiomyosarcoma, undifferentiated pleomorphic sarcoma, synovial sarcoma, malignant peripheral nerve sheath tumor (MPNST), or combinations thereof.

[0047] In some aspects of the above method, the brain cancer is a primary malignant tumor, a brain metastatic malignant tumor, or a combination thereof.

[0048] In some aspects of the above method, the primary malignant tumor is a glioma, medulloblastoma, central nervous system lymphoma, or combination thereof.

[0049] In some aspects of the above method, the metastatic malignant tumor originated from melanoma, breast cancer, lung cancer, colorectal cancer, kidney cancer, or any combination thereof.

[0050] Certain aspects of the presently disclosed subject matter having been stated herein above, which are addressed in whole or in part by the presently disclosed subject matter, other aspects will become evident as the description proceeds when taken in connection with the accompanying Examples as best described herein below.DETAILED DESCRIPTION

[0051] The present disclosure relates to pharmaceutical compositions and methods of treating cancer. In particular, the present disclosure provides pharmaceutical compositions containing elraglusib in combination with at least one other active agent and the use of these composition to treat cancer.DEFINITIONS

[0052] The following terms are used to describe the invention of the present disclosure. In instances where a term is not specifically defined herein, that term is given an art-recognized meaning by those of ordinary skill applying that term in context to its use in describing the present disclosure.

[0053] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. For example, any nomenclatures used in connection with, and techniques of, cell and tissue culture, molecular biology, immunology, microbiology, genetics, and protein and nucleic acid chemistry and hybridization described herein are well known and commonly used in the art. In case of conflict, the present disclosure, including definitions, will control. Exemplary methods and materials are described below, although methods and materials similar or equivalent to those described herein can be used in practice or testing of the embodiments and aspects described herein.

[0054] Compounds and materials are described using standard nomenclature. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which this invention belongs. The following terms are used to describe the invention of the present disclosure. In instances where a term is not specifically defined herein, that term is given an art-recognized meaning by those of ordinary skill applying that term in context to its use in describing the present disclosure.

[0055] The use of the terms “a” and “an” and “the” and similar referents (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. By way of example, "an element" means one element or more than one element.

[0056] As used herein, the term “substantially” means to a great or significant extent, but not completely.

[0057] It should also be understood that, in certain methods described herein that include more than one step or act, the order of the steps or acts of the method is not necessarily limited to the order in which the steps or acts of the method are recited unless the context indicates otherwise. Furthermore, the terms first, second, etc., as used herein are not meant to denote any particular ordering, but simply for convenience to denote a plurality of, for example, layers.

[0058] The phrase “in one embodiment” or “in some embodiments” as used herein does not necessarily refer to the same embodiment, though it may. Furthermore, the phrase “in another embodiment” as used herein does not necessarily refer to a different embodiment, although it may. Thus, as described below, various embodiments of the invention may be readily combined, without departing from the scope or spirit of the invention.

[0059] The terms "comprise(s)," "include(s)," "having," "has," "can," "contain(s)," and variants thereof, as used herein, are intended to be open-ended transitional phrases, terms, or words that do not preclude the possibility of additional acts or structures. The singular forms "a," "and" and "the" include plural references unless the context clearly dictates otherwise. The present disclosure also contemplates other embodiments "comprising," "consisting of," and "consisting essentially of," the embodiments or elements presented herein, whether explicitly set forth or not.

[0060] The terms “about” or “approximately,” as used herein, is inclusive of the stated value and means within an acceptable range of deviation for the particular value as determined by one of ordinary skill in the art, considering the measurement in question and the error associated with measurement of the particular quantity (i.e., the limitations of the measurement system). For example, “about” can mean within one or more standard deviations, or within ± 10% or 5% of the stated value. Recitation of ranges of values are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. All ranges disclosed herein include both end points as discrete values as well as all integers and fractions specified within the range. For example, a range of 0.1-2.0 includes 0.1, 0.2, 0.3, 0.4 . . . 2.0. All methods described herein can be performed in a suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., “such as”), is intended merely to better illustrate the invention and does not pose a limitation on the scope of the invention unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention as used herein.

[0061] Unless otherwise defined herein, scientific, and technical terms used in connection with the present disclosure shall have the meanings that are commonly understood by those of ordinary skill in the art. The meaning and scope of the terms should be clear; in the event, however of any latent ambiguity, definitions provided herein take precedent over any dictionary or extrinsic definition. Further, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular.

[0062] 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 elementslisted 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 embodiment, to B only (optionally including elements other than A); in yet another embodiment, to both A and B (optionally including other elements); etc.

[0063] As used herein in the specification and in the claims, “or” should be understood to have the same meaning as “and / or” as defined above. For example, when separating items in a list, “or” or “and / or” shall be interpreted as being inclusive, e.g., the inclusion of at least one, but also including more than one, of a number or list of elements, and, optionally, additional unlisted items. Only terms clearly indicated to the contrary, such as “only one of’ or “exactly one of’ or, when used in the claims, “consisting of,” will refer to the inclusion of exactly one element of a number or list of elements. In general, the term “or” as used herein shall only be interpreted as indicating exclusive alternatives (e.g., “one or the other but not both”) when preceded by terms of exclusivity, such as “either,” “one of’ “only one of’ or “exactly one of.”

[0064] 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 any one 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.

[0065] The phrase "one or more," as used herein, means at least one, and thus includes individual components as well as mixtures / combinations of the listed components in any combination.

[0066] Other than in the examples, or where otherwise indicated, all numbers expressing quantities of ingredients and / or reaction conditions are to be understood as being modified in all instances by the term "about," meaning within 10% of the indicated number (e.g., "about 10%" means 9%- 11% and "about 2%" means 1.8%-2.2%).

[0067] All percentages and ratios are calculated by weight unless otherwise indicated. All percentages are calculated based on the total composition unless otherwise indicated. Generally, unless otherwise expressly stated herein, "weight" or "amount" as used herein with respect to the percent amount of an ingredient refers to the amount of the raw material comprising the ingredient, wherein the raw material may be described herein to comprise less than and up to 100% activity of the ingredient. Therefore, weight percent of an active in a composition is represented as the amount of raw material containing the active that is used and may or may not reflect the final percentage of the active, wherein the final percentage of the active is dependent on the weight percent of active in the raw material.

[0068] All ranges and amounts given herein are intended to include subranges and amounts using any disclosed point as an end point. Thus, a range of " 1% to 10%, such as 2% to 8%, such as 3% to 5%," is intended to encompass ranges of "1% to 8%," "1% to 5%," "2% to 10%," and so on. All numbers, amounts, ranges, etc., are intended to be modified by the term "about," whether or not so expressly stated. Similarly, a range given of "about 1% to 10%" is intended to have the term "about" modifying both the 1% and the 10% endpoints. Further, it is understood that when an amount of a component is given, it is intended to signify the amount of the active material unless otherwise specifically stated.

[0069] As used herein, the term "administering" means either directly administering one or more of a compound, active or therapeutic agent, composition, or dosage form of the present disclosure or administering a prodrug, derivative or analog which will form an equivalent amount of the active compound(s), active ingredient(s), or substance(s) within the body of a subject or patient.

[0070] As used herein, the term “cancer” refers to a group of diseases characterized by the uncontrolled growth and proliferation of abnormal cells in a subject or patient. These cells have the ability to invade surrounding tissues and spread to distant parts of the body through the bloodand lymphatic systems (metastasis). Cancer disrupts normal bodily functions and can occur in nearly any tissue or organ.

[0071] Examples of cancers include, but are not limited to, pancreatic cancer, malignant bone tumors (e.g., osteosarcoma, Ewing sarcoma, chondrosarcoma), soft tissue malignant tumors (e.g., liposarcoma, leiomyosarcoma, undifferentiated pleomorphic sarcoma, synovial sarcoma, malignant peripheral nerve sheath tumor (MPNST)), brain cancer (e.g., primary malignant tumors such as gliomas, medulloblastomas, central nervous system lymphomas; or metastatic malignant tumors originating from melanoma, breast cancer, lung cancer, colorectal cancer, or kidney cancer), and acute myeloid leukemia (AML).

[0072] As used herein, the term "dosage" refers to the specific amount, concentration, or form of a therapeutic or active agent administered to achieve a desired therapeutic effect in a subject or patient. The term "dosage" may also be used interchangeably with "pharmaceutical composition" to describe a preparation that includes a therapeutically effective amount of one or more active agents, optionally combined with pharmaceutically acceptable carriers, pharmaceutically acceptable excipients, or other components, suitable for administration via a specific route (e.g., oral, intravenous, subcutaneous, or topical). Such compositions may be tailored for use in singledose or multi-dose regimens depending on the intended therapeutic application.

[0073] As used herein, the term “combination” is used in its broadest sense and means that a subject is administered at least two therapeutic or active agents, more particularly a compound disclosed herein and at least one other therapeutic or active agent. More particularly, the term “in combination” refers to the concomitant administration of two (or more) therapeutic or active agents for the treatment of a, e.g., single disease state. As used herein, the therapeutic or active agents may be combined and administered in a single dosage form, may be administered as separate dosage forms at the same time, or may be administered as separate dosage forms that are administered alternately or sequentially on the same or separate days. In one embodiment of the presently disclosed subject matter, the therapeutic or active agents are combined and administered in a single dosage form. In another embodiment, the therapeutic or active agents are administered in separate dosage forms (e.g., wherein it is desirable to vary the amount of one but not the other). The single dosage form may include additional therapeutic or active agents for the treatment of the disease state, such as, for example, cancer.

[0074] Further, the compounds disclosed herein can be administered alone or in combination with adjuvants that enhance stability of the compounds, alone or in combination with one or more therapeutic or active agents, facilitate administration of pharmaceutical compositions containing them in certain embodiments, provide increased dissolution or dispersion, increase inhibitory activity, provide adjunct therapy, and the like, including other active ingredients. Advantageously, such combination therapies utilize lower dosages of the conventional therapeutics, thus avoiding possible toxicity and adverse side effects incurred when those agents are used as monotherapies.

[0075] The timing of administration of a therapeutic or active agent or compound disclosed herein and at least one additional therapeutic agent can be varied so long as the beneficial effects of the combination of these agents are achieved. Accordingly, the phrase “in combination with” refers to the administration of a compound described herein and at least one additional therapeutic or active agent either simultaneously, sequentially, or a combination thereof. Therefore, a subject administered a combination of a compound described herein and at least one additional therapeutic or active agent can receive a compound and at least one additional therapeutic or active agent at the same time (i.e., simultaneously) or at different times (i.e., sequentially, in either order, on the same day or on different days), so long as the effect of the combination of both therapeutic or active agents is achieved in the subject.

[0076] When administered sequentially, the agents can be administered within 1, 5, 10, 30, 60, 120, 180, 240 minutes or longer of one another. In other embodiments, agents administered sequentially, can be administered within 1, 5, 10, 15, 20 or more days of one another. Where the compound described herein and at least one additional therapeutic or active agent are administered simultaneously, they can be administered to the subject as separate pharmaceutical compositions, each comprising either a compound or at least one additional therapeutic or active agent, or they can be administered to a subject as a single pharmaceutical composition comprising both agents.

[0077] When administered in combination, the effective concentration of each of the agents to elicit a particular biological response may be less than the effective concentration of each agent when administered alone, thereby allowing a reduction in the dose of one or more of the agents relative to the dose that would be needed if the agent was administered as a single agent. The effects of multiple agents may, but need not be, additive or synergistic. The agents may be administered multiple times.

[0078] As used herein, the term “effective amount” refers to the amount of a composition (e.g., pharmaceutical composition) sufficient to effect beneficial or desired results. An effective amount can be administered in one or more administrations, applications or dosages and is not intended to be limited to a particular formulation or administration route.

[0079] As used herein, the term “elraglusib” or “9-ING-41” as used interchangeably herein, refers to a Glycogen Synthase Kinase-3 (GSK-3) inhibitor having the chemical name 3-(5-Fluoro- benzofuran-3-yl)-4-(5-methyl-5H-[l,3]dioxolo[4,5f]indol-7-yl)-pyrrole-2, 5-dione and the molecular formula C22H13N2O5F. The chemical structure of elraglusib is shown below in Formula I.Formula I

[0080] Solids forms of elraglusib are described in U.S. Patent No. 11,136,334 and U.S. Patent Publication No. 2022 / 0348591, the contents of each of which are herein incorporated by reference. Additionally, methods for making elraglusib or the solid forms thereof are described in U.S. Patent Nos. 8,207,216 and 11,136,334 and U.S. Patent Publication No. 2022 / 0348591, the contents of which are herein incorporated by reference.

[0081] As used herein, the phrase “FLT3 inhibitor” refers to a therapeutic or active agent or drug designed to target and inhibit the activity of the FMS-like tyrosine kinase 3 (FLT3) protein, a receptor tyrosine kinase frequently mutated or overexpressed in certain cancers, particularly acute myeloid leukemia (AML). FLT3 is involved in the regulation of cell growth and survival, and mutations or overactivity in FLT3 are associated with uncontrolled proliferation and disease progression. Examples of FLT3 inhibitors include, but are not limited to, midostaurin, gilteritinib, quizartinib and any combination thereof. Table A below provides information on the route of administration, the type of FLT3 mutation targeted by each of these inhibitors, anddosage. Methods for making FLT3 inhibitors, such as, midostaurin, gilteritinib and quizartinib are well known in the art.Table A’The dosage of any FLT3 inhibitor recited in this table is merely exemplary and a person skilled in the art would understand that these dosages might need to be adjusted based on the pharmacokinetic and pharmacodynamic interactions resulting from the combination of elraglusib or a pharmaceutically acceptable salt thereof and at least one FLT3 inhibitor contained in a single dosage form of the present disclosure. Additionally, potential synergistic or antagonistic effects may necessitate dose reductions or increases, respectively, to maintain optimal therapeutic efficacy while mitigating adverse events. Furthermore, the combined toxicity profile and potential for overlapping side effects might mandate dose reductions to ensure patient safety.

[0082] The term “FOLFIRINOX” refers to a chemotherapy regimen for treatment of advanced pancreatic cancer. It is made up of the following four drugs: (a) FOL — folinic acid (leucovorin), a vitamin B derivative that modulates / potentiates / reduces the side effects of fluorouracil; (b) F — fluorouracil (5-FU), a pyrimidine analog and antimetabolite which incorporates into the DNA molecule and stops DNA synthesis; (c) IRIN — irinotecan (Camptosar), a topoisomerase inhibitor, which prevents DNA from un-coiling and duplicating; and (d) OX — oxaliplatin (Eloxatin), a platinum-based anti neoplastic agent, which inhibits DNA repair and / or DNA synthesis.

[0083] The term “NALIRIFOX” refers to a chemotherapy regimen used for the treatment of advanced pancreatic cancer. It is composed of the following four drugs: (a) NALIRI — liposomal irinotecan (Onivyde), a formulation of irinotecan in liposomal form, which acts as a topoisomerase inhibitor to prevent DNA uncoiling and duplication; (b) F — fluorouracil (5-FU), a pyrimidine analog and antimetabolite that incorporates into DNA and halts DNA synthesis; (c)LEUCOVORIN — folinic acid, a vitamin B derivative that enhances the effectiveness of fluorouracil and reduces its side effects; and (d) OX — oxaliplatin (Eloxatin), a platinum-based antineoplastic agent that inhibits DNA repair and synthesis.

[0084] As used herein, the phrase “PARP inhibitor” refers to a therapeutic or active agent or drug designed to target and inhibit the activity of poly (ADP -ribose) polymerase (PARP) enzymes, which play a critical role in DNA repair. Inhibiting PARP enzymes prevents cancer cells, particularly those with deficiencies in homologous recombination repair (such as BRCA1 or BRCA2 mutations), from repairing DNA damage, leading to cell death. Examples of PARP inhibitors include, but are not limited to, Olaparib (LYNPARZA), Talazoparib (TALZENNA), Rucaparib (RUBRACA), Niraparib (ZEJULA), and any combination thereof. Table B below provides information on the route of administration, specific targets, and dosage for each of these inhibitors. Methods for making PARP inhibitors, such as Olaparib (LYNPARZA), Talazoparib (TALZENNA), Rucaparib (RUBRACA), and Niraparib (ZEJULA), are well known in the art.Table B'The dosage of any PARP inhibitor recited in this table is merely exemplary and a person skilled in the art would understand that these dosages might need to be adjusted based on the pharmacokinetic and pharmacodynamic interactions resulting from the combination of elraglusib or a pharmaceutically acceptable salt thereof and at least one PARP inhibitor contained in a single dosage form of the present disclosure. Additionally, potential synergistic or antagonistic effects may necessitate dose reductions or increases, respectively, to maintain optimal therapeutic efficacy while mitigating adverse events. Furthermore, the combined toxicity profile and potential for overlapping side effects might mandate dose reductions to ensure patient safety.

[0085] As used herein, the terms “patient” or “subject” refer to organisms to be subject to various tests provided by the technology. The term “subject” includes animals, preferably mammals, including humans. In a preferred embodiment, the subject is a primate. In an even more preferred embodiment, the subject is a human. Further with respect to diagnostic methods, a preferred subject is a vertebrate subject. A preferred vertebrate is warm-blooded; a preferred warm-blooded vertebrate is a mammal. A preferred mammal is most preferably a human. As used herein, the term “subject1includes both human and animal subjects. Thus, veterinary therapeutic uses are provided herein. As such, the present technology provides for the diagnosis of mammals such as humans, as well as those mammals of importance due to being endangered, such as Siberian tigers; of economic im-portance, such as animals raised on farms for consumption by humans; and / or animals of social importance to humans, such as animals kept as pets or in zoos. Examples of such animals include but are not limited to: carnivores such as cats and dogs; swine, including pigs, hogs, and wild boars; ruminants and / or ungulates such as cattle, oxen, sheep, giraffes, deer, goats, bison, and camels; pinnipeds; and horses. Thus, also provided is the diagnosis and treatment of livestock, including, but not limited to, domesticated swine, ruminants, ungulates, horses (including racehorses), and the like.

[0086] As used herein, the term “pharmaceutical composition” refers to one or more therapeutic or active agents in combination with a carrier, inert or active, making the composition especially suitable for diagnostic or therapeutic use in vitro, in vivo, or ex vivo. In some aspects, a pharmaceutical composition further comprise one or more pharmaceutically acceptable carriers and / or pharmaceutically acceptable excipients.

[0087] As used herein, the terms “pharmaceutically acceptable” or “pharmacologically acceptable,” as used herein, refer to compositions that do not substantially produce adverse reactions, e.g., toxic, allergic, or immunological reactions, when administered to a subject.

[0088] As used herein, the term “pharmaceutically acceptable carrier” refers to any of the standard pharmaceutical carriers including, but not limited to, phosphate buffered saline solution, water, emulsions (e.g., such as an oil / water or water / oil emulsions), and various types of wetting agents, any and all solvents, dispersion media, coatings, sodium lauryl sulfate, isotonic and absorption delaying agents, disintegrants (e.g., potato starch or sodium starch glycolate), and the like. The compositions also can include stabilizers and preservatives. For examples of carriers, stabilizers,and adjuvants, see, e.g., Martin, Remington's Pharmaceutical Sciences, 15th Ed., 15 Mack Publ. Co., Easton, Pa. (1975), incorporated herein by reference in its entirety.

[0089] As used herein, the phrase, “pharmaceutically acceptable excipient” refers to a substance that is non-toxic, biologically tolerable, and otherwise biologically suitable for administration to a subject, such as an inert substance, added to a pharmacological composition or otherwise used as a vehicle, carrier, or diluent to facilitate administration of an active ingredient or therapeutic or active agent and that is compatible therewith. Examples of excipients include calcium carbonate, calcium phosphate, various sugars and types of starch, cellulose derivatives, gelatin, vegetable oils, and polyethylene glycols. Pharmaceutically acceptable excipients will be known to those of skill in the art, and include, for example, excipients described in treatises such as, for example, Paul J. Sheskey, et al. (eds), Handbook of Pharmaceutical Excipients, Pharmaceutical Press, 9th Revised edition (October 20, 2020).

[0090] In some embodiments, when administered in combination, the two or more therapeutic or active agents can have a synergistic effect. As used herein, the terms “synergy,” “synergistic,” “synergistically” and derivations thereof, such as in a “synergistic effect” or a “synergistic combination” or a “synergistic composition” refer to circumstances under which the biological activity of a combination of a compound or therapeutic or active agent described herein and at least one additional therapeutic agent is greater than the sum of the biological activities of the respective agents when administered individually. Synergy can be expressed in terms of a “Synergy Index (SI),” which generally can be determined by the method described by F. C. Kull et al., Applied Microbiology 9, 538 (1961), from the ratio determined by:

[0091] Qa / Qv + Qb / Qu = Synergy Index (SI)

[0092] wherein:

[0093] QA is the concentration of a component A, acting alone, which produced an end point in relation to component A;

[0094] Qais the concentration of component A, in a mixture, which produced an end point;

[0095] QB is the concentration of a component B, acting alone, which produced an end point in relation to component B; and

[0096] Qb is the concentration of component B, in a mixture, which produced an end point.

[0097] Generally, when the sum of Qa / QA and Qb / Qu is greater than one, antagonism is indicated. When the sum is equal to one, additivity is indicated. When the sum is less than one, synergism isdemonstrated. The lower the SI, the greater the synergy shown by that particular mixture. Thus, a “synergistic combination” has an activity higher that what can be expected based on the observed activities of the individual components when used alone. Further, a “synergistically effective amount” of a component refers to the amount of the component necessary to elicit a synergistic effect in, for example, another therapeutic agent or active agent present in the composition.

[0098] In general, a “therapeutically effective amount” of a therapeutic or active agent refers to the amount of the agent necessary to elicit the desired biological response. As will be appreciated by those of ordinary skill in the art, the effective amount of a therapeutic or active agent may vary depending on such factors as the desired biological endpoint, the therapeutic or active agent to be delivered, the composition of the pharmaceutical composition, the target tissue or cell, and the like. In some embodiments, the term “therapeutically effective amount” refers to an amount sufficient to reduce or ameliorate the severity, duration, progression, or onset of a disease, disorder, or condition, or one or more symptoms thereof; prevent the advancement of a disease, disorder, or condition, cause the regression of a disease, disorder, or condition; prevent the recurrence, development, onset or progression of a symptom associated with a disease, disorder, or condition, or enhance or improve the prophylactic or therapeutic effect(s) of another therapy.

[0099] As used herein, whether by themselves or in conjunction with another term or terms, "treats," "treating," "treated," and "treatment," refer to and include ameliorative, palliative, and / or curative uses and results, or any combination thereof. In other embodiments, the methods described herein can be used prophylactically, that is, preventatively. It should be understood that "prophylaxis" or a prophylactic use or result do not refer to nor require absolute or total prevention (i.e., a 100% preventative or protective use or result). As used herein, prophylaxis or a prophylactic (preventative) use or result refers to uses and results in which administration of a compound or composition diminishes or reduces the severity of a particular condition, symptom, disorder, or disease described herein; diminishes or reduces the likelihood of experiencing a particular condition, symptom, disorder, or disease described herein; or delays the onset or relapse (reoccurrence) of a particular condition, symptom, disorder, or disease described herein; or any combination of the foregoing.I. Pharmaceutical Compositions

[0100] Embodiments of the present disclosure relate to one or more pharmaceutical compositions. In some aspects, the present disclosure relates to one or a single pharmaceuticalcomposition (e.g., one or a single dosage form). In other aspects, the present disclosure relates to two pharmaceutical compositions (e.g., two or more dosage forms). In yet other aspects, the present disclosure relates to three pharmaceutical compositions (e.g., three dosage forms). In still other aspects, the present disclosure relates to four pharmaceutical compositions (e.g., four dosage forms). In yet further aspects, the present disclosure relates to five pharmaceutical compositions (e.g., five dosage forms). In still yet further aspects, the present disclosure relates to six pharmaceutical compositions (e.g., six dosage forms). In yet further aspects, the present disclosure relates to seven pharmaceutical compositions (e.g., seven dosage forms). In still further aspects, the present disclosure relates to eight pharmaceutical compositions (e.g., eight dosage forms). In yet further aspects, the present disclosure relates to nine pharmaceutical compositions (e.g., nine dosage forms). In still yet further aspects, the present disclosure relates to ten pharmaceutical compositions (e.g., ten dosage forms). In still further aspects, the one or more pharmaceutical compositions of the present disclosure further comprise one or more pharmaceutically acceptable excipients.

[0101] More specifically, the present disclosure relates to pharmaceutical compositions comprising a combination of a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof; and (b) a therapeutically effective amount of at least one additional therapeutic or active agent. In some aspects, (a) and (b) are in a single pharmaceutical composition or a single dosage form. In still other aspects, (a) and (b) are in separate pharmaceutical compositions or dosage forms. In yet still other aspect aspects, the at least one additional therapeutic or active agent is a therapeutically effective amount of:

[0102] Oxaliplatin + Liposomal irinotecan + 5-fluorouracil (“5-FU”) + Leucovorin (NALIRIFOX);

[0103] Oxaliplatin + Irinotecan + 5-FU + Leucovorin (FOLFIRINOX);

[0104] ifosfamide;

[0105] ifosfamide and topotecan;

[0106] cyclophosphamide and topotecan;

[0107] carmustine;

[0108] procarbazine;

[0109] cytarabine;

[0110] cytarabine and daunorubicin;

[0111] gemcitabine and cisplatin;

[0112] gemcitabine, cisplatin, and at least one PARP inhibitor; or

[0113] at least one FLT3 inhibitor.

[0114] In some aspects, the one or more pharmaceutical compositions are formulated for simultaneous, sequential, and / or separate administration. In yet further aspects, the one or more pharmaceutical compositions are suitable for oral administration, intrathecal administration and / or intravenous administration to a subject. In yet further aspects, the one or more pharmaceutical compositions are formulated for simultaneous, sequential, and / or separate administration and is suitable for oral administration, intrathecal administration and / or intravenous administration to a subject.

[0115] In some aspects, the pharmaceutical composition comprises a combination of a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof; and (b) a therapeutically effective amount of each of oxaliplatin + liposomal irinotecan + 5-FU + leucovorin (NALIRIFOX). In in other aspects, a first pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a second pharmaceutical composition comprises a therapeutically effective amount of each of oxaliplatin, liposomal irinotecan, 5-FU, and leucovorin (NALIRIFOX). In yet other aspects, a first pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof, a second pharmaceutical composition comprises a therapeutically effective amount of oxaliplatin, a third pharmaceutical composition comprises a therapeutically effective amount of liposomal irinotecan, a fourth pharmaceutical composition comprises a therapeutically effective amount of 5-FU, and a fifth pharmaceutical composition comprises a therapeutically effective amount of leucovorin. In yet further aspects, the one or more pharmaceutical compositions are suitable for oral administration, intrathecal administration and / or intravenous administration to a subject. In yet further aspects, the one or more pharmaceutical compositions formulated for simultaneous, sequential, and / or separate administration and is suitable for oral administration, intrathecal administration and / or intravenous administration to a subject.

[0116] In yet other aspects, the pharmaceutical composition comprises a combination of a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof; and (b) a therapeutically effective amount of each of oxaliplatin, irinotecan, 5-FU, and leucovorin(FOLFIRINOX). In in other aspects, a first pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a second pharmaceutical composition comprises a therapeutically effective amount of each of oxaliplatin + irinotecan + 5-FU + leucovorin (FOLFIRINOX). In yet other aspects, a first pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof, a second pharmaceutical composition comprises a therapeutically effective amount of oxaliplatin, a third pharmaceutical composition comprises a therapeutically effective amount of irinotecan, a fourth pharmaceutical composition comprises a therapeutically effective amount of 5-FU, and a fifth pharmaceutical composition comprises a therapeutically effective amount of leucovorin. In yet further aspects, the one or more pharmaceutical compositions are suitable for oral administration, intrathecal administration and / or intravenous administration to a subject. In yet further aspects, the pharmaceutical composition is formulated for simultaneous, sequential, and / or separate administration and is suitable for oral administration, intrathecal administration and / or intravenous administration to a subject.

[0117] In yet other aspects, the pharmaceutical composition comprises a combination of a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof; and (b) a therapeutically effective amount of ifosfamide. In in other aspects, a first pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a second pharmaceutical composition comprises a therapeutically effective amount of ifosfamide. In yet further aspects, the one or more pharmaceutical compositions are suitable for oral administration, intrathecal administration and / or intravenous administration to a subject. In yet further aspects, the one or more pharmaceutical compositions are formulated for simultaneous, sequential, and / or separate administration and is suitable for oral administration, intrathecal administration and / or intravenous administration to a subject.

[0118] In yet other aspects, the pharmaceutical composition comprises a combination of a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof; and (b) a therapeutically effective amount of ifosfamide and therapeutically effective amount of topotecan. In in other aspects, a first pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a second pharmaceutical composition comprises a therapeutically effective amount of ifosfamide. In yet further aspects, the one or more pharmaceutical compositions are suitable for oral administration,intrathecal administration and / or intravenous administration to a subject. In yet further aspects, the one or more pharmaceutical compositions are formulated for simultaneous, sequential, and / or separate administration and is suitable for oral administration, intrathecal administration and / or intravenous administration to a subject.

[0119] In yet other aspects, the pharmaceutical composition comprises a combination of a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof; and (b) a therapeutically effective amount of cyclophosphamide and a therapeutically effective amount of topotecan. In in other aspects, a first pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a second pharmaceutical composition comprises a therapeutically effective amount of cyclophosphamide and a therapeutically effective amount of topotecan. In yet other aspects, a first pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof, a second pharmaceutical composition comprises a therapeutically effective amount of cyclophosphamide, and a third pharmaceutical composition comprises a therapeutically effective amount of topotecan. In yet further aspects, the one or more pharmaceutical compositions are suitable for oral administration, intrathecal administration and / or intravenous administration to a subject. In yet further aspects, the one or more pharmaceutical compositions are formulated for simultaneous, sequential, and / or separate administration and is suitable for oral administration, intrathecal administration and / or intravenous administration to a subject.

[0120] In yet other aspects, the pharmaceutical composition comprises a combination of a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof; and (b) a therapeutically effective amount of carmustine. In in other aspects, a first pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a second pharmaceutical composition comprises a therapeutically effective amount of carmustine. In yet further aspects, the one or more pharmaceutical compositions are suitable for oral administration, intrathecal administration and / or intravenous administration to a subject. In yet further aspects, the one or more pharmaceutical compositions are formulated for simultaneous, sequential, and / or separate administration and is suitable for oral administration, intrathecal administration and / or intravenous administration to a subject.

[0121] In yet other aspects, the pharmaceutical composition comprises a combination of a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof; and(b) a therapeutically effective amount of procarbazine. Tn in other aspects, a first pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a second pharmaceutical composition comprises a therapeutically effective amount of procarbazine. In yet further aspects, the one or more pharmaceutical compositions are suitable for oral administration, intrathecal administration and / or intravenous administration to a subject. In yet further aspects, the one or more pharmaceutical compositions are formulated for simultaneous, sequential, and / or separate administration and is suitable for oral administration, intrathecal administration and / or intravenous administration to a subject.

[0122] In yet other aspects, the pharmaceutical composition comprises a combination of a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof; and (b) a therapeutically effective amount of cytarabine. In in other aspects, a first pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a second pharmaceutical composition comprises a therapeutically effective amount of cytarabine. In yet further aspects, the one or more pharmaceutical compositions are suitable for oral administration, intrathecal administration and / or intravenous administration to a subject. In yet further aspects, the one or more pharmaceutical compositions are formulated for simultaneous, sequential, and / or separate administration and is suitable for oral administration, intrathecal administration and / or intravenous administration to a subject.

[0123] In yet other aspects, the pharmaceutical composition comprises a combination of a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof; and (b) a therapeutically effective amount of cytarabine and a therapeutically effective amount of daunorubicin. In still other aspects, a first pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof, a second pharmaceutical composition comprises a therapeutically effective amount of cytarabine, and a third pharmaceutical composition comprises a therapeutically effective amount of daunorubicin. In yet further aspects, the one or more pharmaceutical compositions are suitable for oral administration, intrathecal administration and / or intravenous administration to a subject. In yet further aspects, the one or more pharmaceutical compositions are formulated for simultaneous, sequential, and / or separate administration and is suitable for oral administration, intrathecal administration and / or intravenous administration to a subject.

[0124] In yet other aspects, the pharmaceutical composition comprises a combination of a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof; and (b) a therapeutically effective amount of gemcitabine and a therapeutically effective amount of cisplatin. In other aspects, a first pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a second pharmaceutical composition comprises a therapeutically effective amount of gemcitabine and a therapeutically effective amount of cisplatin. In yet further aspects, a first pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof, a second pharmaceutical composition comprises a therapeutically effective amount of gemcitabine, and a third pharmaceutical composition comprises a therapeutically effective amount of cisplatin. In yet further aspects, the one or more pharmaceutical compositions are suitable for oral administration, intrathecal administration and / or intravenous administration to a subject. In yet further aspects, the one or more pharmaceutical compositions are formulated for simultaneous, sequential, and / or separate administration and is suitable for oral administration, intrathecal administration and / or intravenous administration to a subject.

[0125] In yet other aspects, the pharmaceutical composition comprises a combination of a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof; and (b) a therapeutically effective amount of gemcitabine, a therapeutically effective amount of cisplatin and a therapeutically effective amount of at least one PARP inhibitor. In other aspects, a first pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a second pharmaceutical composition comprises a therapeutically effective amount of gemcitabine, a therapeutically effective amount of cisplatin, and a therapeutically effective amount of at least one PARP inhibitor. In yet further aspects, a first pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof, a second pharmaceutical composition comprises a therapeutically effective amount of gemcitabine, a third pharmaceutical composition comprises a therapeutically effective amount of cisplatin, and a fourth pharmaceutical composition comprises a therapeutically effective amount of at least one PARP inhibitor. In some aspects, the at least one PARP inhibitor is olaparib, talazoparib, rucaparib, or any combination thereof. In yet further aspects, the one or more pharmaceutical compositions are suitable for oral administration, intrathecal administration and / or intravenous administration to a subject. In yet further aspects, theone or more pharmaceutical compositions are formulated for simultaneous, sequential, and / or separate administration and is suitable for oral administration, intrathecal administration and / or intravenous administration to a subject.

[0126] In yet other aspects, the pharmaceutical composition comprises a combination of a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof; and (b) a therapeutically effective amount of at least one FLT3 inhibitor. In other aspects, a first pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a second pharmaceutical composition comprises a therapeutically effective amount of at least one FLT3 inhibitor. In some aspects, the FLT3 inhibitor is midostaurin, gilteritinib, quizartinib, or any combinations thereof. In yet further aspects, the one or more pharmaceutical compositions are suitable for oral administration, intrathecal administration and / or intravenous administration to a subject. In yet further aspects, the one or more pharmaceutical compositions are formulated for simultaneous, sequential, and / or separate administration and is suitable for oral administration, intrathecal administration and / or intravenous administration to a subject.

[0127] In some embodiments, the therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof is from about 5 mg / kg to about 50 mg / kg. In some embodiments, the therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof is about 5 mg / kg. In some embodiments, the therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof is about 10 mg / kg. In some embodiments, the therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof is about 15 mg / kg. In some embodiments, the therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof is about 20 mg / kg. In some embodiments, the therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof is about 25 mg / kg. In some embodiments, the therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof is 30 mg / kg. In some embodiments, the therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof is about 35 mg / kg. In some embodiments, the therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof is about 40 mg / kg. In some embodiments, the therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof is about 45 mg / kg. In someembodiments, the therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof is about 50 mg / kg.

[0128] In some embodiments, the therapeutically effective amount of NALIRIFOX (oxaliplatin + liposomal irinotecan + 5-FU + leucovorin) is from about 40 mg / m2to about 2400 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is from about 40 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 45 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 50 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 55 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 60 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 65 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 70 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 75 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 80 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 85 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 90 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 95 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 100 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 150 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 200 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 250 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 300 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 350 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 400 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 450 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 500 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 600 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 700 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 800 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 900 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 1000 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 1100 mg / m2. Insome embodiments, the therapeutically effective amount of NALIRIFOX is about 1200 mg / m2In some embodiments, the therapeutically effective amount of NALIRIFOX is about 1300 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 1400 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 1500 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 1600 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 1700 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 1800 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 1900 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 2000 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 2100 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 2200 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 2300 mg / m2. In some embodiments, the therapeutically effective amount of NALIRIFOX is about 2400 mg / m2.

[0129] In some embodiments, the therapeutically effective amount of liposomal irinotecan is from about 30 mg / m2to about 150 mg / m2. In some embodiments, the therapeutically effective amount of liposomal irinotecan is about 30 mg / m2. In some embodiments, the therapeutically effective amount of liposomal irinotecan is about 40 mg / m2. In some embodiments, the therapeutically effective amount of liposomal irinotecan is about 50 mg / m2. In some embodiments, the therapeutically effective amount of liposomal irinotecan is about 60 mg / m2. In some embodiments, the therapeutically effective amount of liposomal irinotecan is about 70 mg / m2. In some embodiments, the therapeutically effective amount of liposomal irinotecan is about 80 mg / m2. In some embodiments, the therapeutically effective amount of liposomal irinotecan is about 90 mg / m2. In some embodiments, the therapeutically effective amount of liposomal irinotecan is about 100 mg / m2. In some embodiments, the therapeutically effective amount of liposomal irinotecan is about 110 mg / m2. In some embodiments, the therapeutically effective amount of liposomal irinotecan is about 120 mg / m2. In some embodiments, the therapeutically effective amount of liposomal irinotecan is about 130 mg / m2. In some embodiments, the therapeutically effective amount of liposomal irinotecan is about 140 mg / m2. In some embodiments, the therapeutically effective amount of liposomal irinotecan is about 150 mg / m2.

[0130] In some embodiments, the therapeutically effective amount of oxaliplatin is from about 30 mg / m2to about 120 mg / m2. In some embodiments, the therapeutically effective amount of 1oxaliplatin is about 30 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 35 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 40 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 45 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 50 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin about 55 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 60 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin about 65 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 70 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin about 75 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 80 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin IS about 85 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 90 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 95 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 100 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 105 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin IS about 110 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 115 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 120 mg / m2.

[0131] In some embodiments, the therapeutically effective amount of leucovorin is from about100 mg / m2to about 1000 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin is about 100 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin is about 150 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin is about 200 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin is about 250 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin is about 300 mg / m2. In some embodiments, the therapeutically effective amount ofLeucovorin is about 350 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin is about 400 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin IS about 450 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin is about 500 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin is about 550 mg / m2. In some embodiments, the therapeutically effective amount ofleucovorin is about 600 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin is about 650 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin is about 700 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin is about 750 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin is about 800 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin is about 850 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin is about 900 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin is about 950 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin is about 1000 mg / m2.

[0132] In some embodiments, the therapeutically effective amount of 5 -fluorouracil (5-FU) is from about 200 mg / m2to about 3000 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 200 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 250 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 300 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 350 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 400 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 450 mg / m2In some embodiments, the therapeutically effective amount of 5-FU is about 500 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 550 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 600 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 650 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 700 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 750 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 800 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 850 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 900 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 950 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 1000 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 1100 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 1200 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 1300 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 1400 mg / m2. In someembodiments, the therapeutically effective amount of 5-FU is about 1500 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 1600 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 1700 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 1800 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 1900 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 2000 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 2100 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 2200 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 2300 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 2400 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 2500 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 2600 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 2700 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 2800 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 2900 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 3000 mg / m2.

[0133] In some embodiments, the therapeutically effective amount of liposomal irinotecan is about 50 mg / m2, the therapeutically effective amount of oxaliplatin is about 60 mg / m2, the therapeutically effective amount of leucovorin is about 400 mg / m2, and the therapeutically effective amount of 5-FU is about 2400 mg / m2.

[0134] In some embodiments, the therapeutically effective amount of FOLFIRINOX (oxaliplatin + irinotecan + 5-FU + leucovorin) is from about 40 mg / m2to about 2400 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 40 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 45 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 50 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 55 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 60 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 65 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 70 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 75 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 80 mg / m2. In someembodiments, the therapeutically effective amount of FOLFIRINOX is about 85 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 90 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 95 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 100 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 150 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 200 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 250 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 300 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 350 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 400 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 450 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 500 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 600 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 700 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 800 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 900 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 1000 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 1100 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 1200 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 1300 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 1400 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 1500 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 1600 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 1700 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 1800 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 1900 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 2000 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 2100 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 2200 mg / m2. In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 2300 mg / m2.In some embodiments, the therapeutically effective amount of FOLFIRINOX is about 2400 mg / m2.

[0135] In some embodiments, the therapeutically effective amount of oxaliplatin is from about 30 mg / m2to about 120 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 30 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 35 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 40 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 45 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 50 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 55 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 60 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 65 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 70 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 75 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 80 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 85 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 90 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 95 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 100 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 105 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 110 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 115 mg / m2. In some embodiments, the therapeutically effective amount of oxaliplatin is about 120 mg / m2.

[0136] In some embodiments, the therapeutically effective amount of irinotecan is from about 100 mg / m2to about 400 mg / m2. In some embodiments, the therapeutically effective amount of irinotecan is about 100 mg / m2. In some embodiments, the therapeutically effective amount of irinotecan is about 110 mg / m2. In some embodiments, the therapeutically effective amount of irinotecan is about 120 mg / m2. In some embodiments, the therapeutically effective amount of irinotecan is about 130 mg / m2. In some embodiments, the therapeutically effective amount of irinotecan is about 140 mg / m2. In some embodiments, the therapeutically effective amount of irinotecan is about 150 mg / m2. In some embodiments, the therapeutically effective amount ofirinotecan is about 160 mg / m2. In some embodiments, the therapeutically effective amount of irinotecan is about 170 mg / m2. In some embodiments, the therapeutically effective amount of irinotecan is about 180 mg / m2. In some embodiments, the therapeutically effective amount of irinotecan is about 190 mg / m2. In some embodiments, the therapeutically effective amount of irinotecan is about 200 mg / m2. In some embodiments, the therapeutically effective amount of irinotecan is about 210 mg / m2. In some embodiments, the therapeutically effective amount of irinotecan is about 220 mg / m2. In some embodiments, the therapeutically effective amount of irinotecan is about 230 mg / m2. In some embodiments, the therapeutically effective amount of irinotecan is about 240 mg / m2. In some embodiments, the therapeutically effective amount of irinotecan is about 250 mg / m2. In some embodiments, the therapeutically effective amount of irinotecan is about 260 mg / m2. In some embodiments, the therapeutically effective amount of irinotecan is about 270 mg / m2. In some embodiments, the therapeutically effective amount of irinotecan is about 280 mg / m2. In some embodiments, the therapeutically effective amount of irinotecan is about 290 mg / m2. In some embodiments, the therapeutically effective amount of irinotecan is about 300 mg / m2. In some embodiments, the therapeutically effective amount of irinotecan is about 310 mg / m2. In some embodiments, the therapeutically effective amount of irinotecan is about 320 mg / m2. In some embodiments, the therapeutically effective amount of irinotecan is about 330 mg / m2. In some embodiments, the therapeutically effective amount of irinotecan is about 340 mg / m2. In some embodiments, the therapeutically effective amount of irinotecan is about 350 mg / m2. In some embodiments, the therapeutically effective amount of irinotecan is about 360 mg / m2. In some embodiments, the therapeutically effective amount of irinotecan is about 370 mg / m2. In some embodiments, the therapeutically effective amount of irinotecan is about 380 mg / m2. In some embodiments, the therapeutically effective amount of irinotecan is about 390 mg / m2. In some embodiments, the therapeutically effective amount of irinotecan is about 400 mg / m2.

[0137] In some embodiments, the therapeutically effective amount of leucovorin is from about 100 mg / m2to about 1000 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin is about 100 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin is about 150 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin is about 200 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin is about 250 mg / m2. In some embodiments, the therapeutically effective amount ofleucovorin is about 300 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin is about 350 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin is about 400 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin is about 450 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin about 500 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin about 550 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin about 600 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin about 650 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin about 700 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin about 750 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin about 800 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin is about 850 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin is about 900 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin is about 950 mg / m2. In some embodiments, the therapeutically effective amount of leucovorin is about 1000 mg / m2.In some embodiments, the therapeutically effective amount of 5 -fluorouracil (5-FU) is from about 200 mg / m2to about 3000 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 200 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 250 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 300 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 350 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 400 mg / m2In some embodiments, the therapeutically effective amount of 5-FU is about 450 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 500 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 550 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 600 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 650 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 700 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 750 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 800 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 850 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 900 mg / m2. In someembodiments, the therapeutically effective amount of 5-FU is about 950 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 1000 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 1100 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 1200 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 1300 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 1400 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 1500 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 1600 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 1700 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 1800 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 1900 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 2000 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 2100 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 2200 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 2300 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 2400 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 2500 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 2600 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 2700 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 2800 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 2900 mg / m2. In some embodiments, the therapeutically effective amount of 5-FU is about 3000 mg / m2.

[0138] In some embodiments, as an i.v. infusion, the therapeutically effective amount of oxaliplatin is about 85 mg / m2, the therapeutically effective amount of irinotecan is about 180 mg / m2, the therapeutically effective amount of leucovorin is about 200 mg / m2, followed by a bolus of about 400 mg / m25-FU and a 46-hour continuous infusion of about 2400 mg / m25-FU.

[0139] In some embodiments, the therapeutically effective amount of ifosfamide is from about 0.5 g / m2to about 5 g / m2. In some embodiments, the therapeutically effective amount of ifosfamide is about 0.5 g / m2. In some embodiments, the therapeutically effective amount of ifosfamide is about 0.75 g / m2. In some embodiments, the therapeutically effective amount of ifosfamide is about 1.0 g / m2. In some embodiments, the therapeutically effective amount of ifosfamide is about 1.5g / m2. In some embodiments, the therapeutically effective amount of ifosfamide is about 2.0 g / m2In some embodiments, the therapeutically effective amount of ifosfamide is about 2.5 g / m2. In some embodiments, the therapeutically effective amount of ifosfamide is about 3.0 g / m2. In some embodiments, the therapeutically effective amount of ifosfamide is about 3.5 g / m2. In some embodiments, the therapeutically effective amount of ifosfamide is about 4.0 g / m2. In some embodiments, the therapeutically effective amount of ifosfamide is about 4.5 g / m2. In some embodiments, the therapeutically effective amount of ifosfamide is about 5.0 g / m2.

[0140] In some embodiments, the therapeutically effective amount of cyclophosphamide is from about 1 mg / kg to about 75 mg / kg. In some embodiments, the therapeutically effective amount of cyclophosphamide is about 1 mg / kg. In some embodiments, the therapeutically effective amount of cyclophosphamide is about 2 mg / kg. In some embodiments, the therapeutically effective amount of cyclophosphamide is about 3 mg / kg. In some embodiments, the therapeutically effective amount of cyclophosphamide is about 4 mg / kg. In some embodiments, the therapeutically effective amount of cyclophosphamide is about 5 mg / kg. In some embodiments, the therapeutically effective amount of cyclophosphamide is about 10 mg / kg. In some embodiments, the therapeutically effective amount of cyclophosphamide is about 15 mg / kg. In some embodiments, the therapeutically effective amount of cyclophosphamide is about 20 mg / kg. In some embodiments, the therapeutically effective amount of cyclophosphamide is about 25 mg / kg. In some embodiments, the therapeutically effective amount of cyclophosphamide is about 30 mg / kg. In some embodiments, the therapeutically effective amount of cyclophosphamide is about 35 mg / kg. In some embodiments, the therapeutically effective amount of cyclophosphamide is about 40 mg / kg. In some embodiments, the therapeutically effective amount of cyclophosphamide is about 45 mg / kg. In some embodiments, the therapeutically effective amount of cyclophosphamide is about 50 mg / kg. In some embodiments, the therapeutically effective amount of cyclophosphamide is about 55 mg / kg. In some embodiments, the therapeutically effective amount of cyclophosphamide is about 60 mg / kg. In some embodiments, the therapeutically effective amount of cyclophosphamide is about 65 mg / kg. In some embodiments, the therapeutically effective amount of cyclophosphamide is about 70 mg / kg. In some embodiments, the therapeutically effective amount of cyclophosphamide is about 75 mg / kg.

[0141] In some embodiments, the therapeutically effective amount of topotecan is from about 0.5 mg / m2to about 3 mg / m2. In some embodiments, the therapeutically effective amount of topotecanis about 0.5 mg / m2. In some embodiments, the therapeutically effective amount of topotecan is about 1.0 mg / m2. In some embodiments, the therapeutically effective amount of topotecan is about 1.5 mg / m2. In some embodiments, the therapeutically effective amount of topotecan is about 2.0 mg / m2. In some embodiments, the therapeutically effective amount of topotecan is about 2.5 mg / m2. In some embodiments, the therapeutically effective amount of topotecan is about 3.0 mg / m2.

[0142] In some embodiments, the therapeutically effective amount of carmustine is from about 50 mg / m2to about 1 g / m2. In some embodiments, the therapeutically effective amount of carmustine is about 75 mg / m2. In some embodiments, the therapeutically effective amount of carmustine is about 100 mg / m2. In some embodiments, the therapeutically effective amount of carmustine is about 150 mg / m2. In some embodiments, the therapeutically effective amount of carmustine is about 200 mg / m2. In some embodiments, the therapeutically effective amount of carmustine is about 250 mg / m2. In some embodiments, the therapeutically effective amount of carmustine is about 300 mg / m2. In some embodiments, the therapeutically effective amount of carmustine is about 350 mg / m2. In some embodiments, the therapeutically effective amount of carmustine is about 400 mg / m2. In some embodiments, the therapeutically effective amount of carmustine is about 500 mg / m2. In some embodiments, the therapeutically effective amount of carmustine is about 600 mg / m2. In some embodiments, the therapeutically effective amount of carmustine is about 700 mg / m2. In some embodiments, the therapeutically effective amount of carmustine is about 800 mg / m2. In some embodiments, the therapeutically effective amount of carmustine is about 900 mg / m2. In some embodiments, the therapeutically effective amount of carmustine is about 1 g / m2.

[0143] In some embodiments, the therapeutically effective amount of procarbazine is from about1 mg / kg to about 10 mg / kg. In some embodiments, the therapeutically effective amount of procarbazine is about 1 mg / kg. In some embodiments, the therapeutically effective amount of procarbazine is about 2 mg / kg. In some embodiments, the therapeutically effective amount of procarbazine is about 3 mg / kg. In some embodiments, the therapeutically effective amount of procarbazine is about 4 mg / kg. In some embodiments, the therapeutically effective amount of procarbazine is about 5 mg / kg. In some embodiments, the therapeutically effective amount of procarbazine is about 6 mg / kg. In some embodiments, the therapeutically effective amount of procarbazine is about 7 mg / kg. In some embodiments, the therapeutically effective amount ofprocarbazine is about 8 mg / kg. In some embodiments, the therapeutically effective amount of procarbazine is about 9 mg / kg. In some embodiments, the therapeutically effective amount of procarbazine is about 10 mg / kg.

[0144] In some embodiments, the therapeutically effective amount of cytarabine is from about 1 mg / m2to about 5 g / m2. In some embodiments, the therapeutically effective amount of cytarabine is about 1 mg / m2. In some embodiments, the therapeutically effective amount of cytarabine is about 2 mg / m2. In some embodiments, the therapeutically effective amount of cytarabine is about 3 mg / m2. In some embodiments, the therapeutically effective amount of cytarabine is about 4 mg / m2. In some embodiments, the therapeutically effective amount of cytarabine is about 5 mg / m2.

[0145] In some embodiments, the therapeutically effective amount of daunorubicin is from about 40 mg / m2to about 900 mg / m2. In some embodiments, the therapeutically effective amount of daunorubicin is about 40 mg / m2. In some embodiments, the therapeutically effective amount of daunorubicin is about 45 mg / m2. In some embodiments, the therapeutically effective amount of daunorubicin is about 50 mg / m2. In some embodiments, the therapeutically effective amount of daunorubicin is about 55 mg / m2. In some embodiments, the therapeutically effective amount of daunorubicin is about 60 mg / m2. In some embodiments, the therapeutically effective amount of daunorubicin is about 65 mg / m2. In some embodiments, the therapeutically effective amount of daunorubicin is about 70 mg / m2. In some embodiments, the therapeutically effective amount of daunorubicin is about 75 mg / m2. In some embodiments, the therapeutically effective amount of daunorubicin is about 80 mg / m2. In some embodiments, the therapeutically effective amount of daunorubicin is about 85 mg / m2. In some embodiments, the therapeutically effective amount of daunorubicin is about 90 mg / m2. In some embodiments, the therapeutically effective amount of daunorubicin is about 95 mg / m2. In some embodiments, the therapeutically effective amount of daunorubicin is about 100 mg / m2. In some embodiments, the therapeutically effective amount of daunorubicin is about 200 mg / m2. In some embodiments, the therapeutically effective amount of daunorubicin is about 300 mg / m2. In some embodiments, the therapeutically effective amount of daunorubicin is about 400 mg / m2. In some embodiments, the therapeutically effective amount of daunorubicin is about 500 mg / m2. In some embodiments, the therapeutically effective amount of daunorubicin is about 600 mg / m2. In some embodiments, the therapeutically effective amount of daunorubicin is about 700 mg / m2. In some embodiments, the therapeutically effective amount ofdaunorubicin is about 800 mg / m2. In some embodiments, the therapeutically effective amount of daunorubicin is about 900 mg / m2.

[0146] In some embodiments, the therapeutically effective amount of olaparib is from about 300 mg to about 600 mg. In some embodiments, the therapeutically effective amount of olaparib is about 300 mg. In some embodiments, the therapeutically effective amount of olaparib is about 350 mg. In some embodiments, the therapeutically effective amount of olaparib is about 400 mg. In some embodiments, the therapeutically effective amount of olaparib is about 450 mg. In some embodiments, the therapeutically effective amount of olaparib is about 500 mg. In some embodiments, the therapeutically effective amount of olaparib is about 550 mg. In some embodiments, the therapeutically effective amount of olaparib is about 600 mg.

[0147] In some embodiments, the therapeutically effective amount of talazoparib is from about 0.1 mg to about 2 mg. In some embodiments, the therapeutically effective amount of talazoparib is about 0.1 mg. In some embodiments, the therapeutically effective amount of talazoparib is about 0.2 mg. In some embodiments, the therapeutically effective amount of talazoparib is about 0.3 mg. In some embodiments, the therapeutically effective amount of talazoparib is about 0.4 mg. In some embodiments, the therapeutically effective amount of talazoparib is about 0.5 mg. In some embodiments, the therapeutically effective amount of talazoparib is about 0.6 mg. In some embodiments, the therapeutically effective amount of talazoparib is about 0. mg. In some embodiments, the therapeutically effective amount of talazoparib is about 1.5 mg. In some embodiments, the therapeutically effective amount of talazoparib is about 2.0 mg.

[0148] In some embodiments, the therapeutically effective amount of rucaparib is from about 200 mg to about 600 mg. In some embodiments, the therapeutically effective amount of rucaparib is about 200 mg. In some embodiments, the therapeutically effective amount of rucaparib is about 250 mg. In some embodiments, the therapeutically effective amount of rucaparib is about 300 mg.In some embodiments, the therapeutically effective amount of rucaparib is about 350 mg. In some embodiments, the therapeutically effective amount of rucaparib is about 400 mg. In some embodiments, the therapeutically effective amount of rucaparib is about 450 mg. In some embodiments, the therapeutically effective amount of rucaparib is about 500 mg. In some embodiments, the therapeutically effective amount of rucaparib is about 550 mg. In some embodiments, the therapeutically effective amount of rucaparib is about 600 mg.

[0149] In some embodiments, the therapeutically effective amount of niraparib is from about 200 mg to about 400 mg. In some embodiments, the therapeutically effective amount of niraparib is about 200 mg. In some embodiments, the therapeutically effective amount of niraparib is about 250 mg. In some embodiments, the therapeutically effective amount of niraparib is about 300 mg.In some embodiments, the therapeutically effective amount of niraparib is about 350 mg. In some embodiments, the therapeutically effective amount of niraparib is about 400 mg.

[0150] In some embodiments, the therapeutically effective amount of gilteritinib is from about20 mg to about 150 mg. In some embodiments, the therapeutically effective amount of gilteritinib is about 20 mg. In some embodiments, the therapeutically effective amount of gilteritinib is about25 mg. In some embodiments, the therapeutically effective amount of gilteritinib is about 30 mg.In some embodiments, the therapeutically effective amount of gilteritinib is about 35 mg. In some embodiments, the therapeutically effective amount of gilteritinib is about 40 mg. In some embodiments, the therapeutically effective amount of gilteritinib is about 45 mg. In some embodiments, the therapeutically effective amount of gilteritinib is about 50 mg. In some embodiments, the therapeutically effective amount of gilteritinib is about 55 mg. In some embodiments, the therapeutically effective amount of gilteritinib is about 60 mg. In some embodiments, the therapeutically effective amount of gilteritinib is about 65 mg. In some embodiments, the therapeutically effective amount of gilteritinib is about 70 mg. In some embodiments, the therapeutically effective amount of gilteritinib is about 75 mg. In some embodiments, the therapeutically effective amount of gilteritinib is about 80 mg. In some embodiments, the therapeutically effective amount of gilteritinib is about 85 mg. In some embodiments, the therapeutically effective amount of gilteritinib is about 90 mg. In some embodiments, the therapeutically effective amount of gilteritinib is about 95 mg. In some embodiments, the therapeutically effective amount of gilteritinib is about 100 mg. In some embodiments, the therapeutically effective amount of gilteritinib is about 105 mg. In some embodiments, the therapeutically effective amount of gilteritinib is about 110 mg. In some embodiments, the therapeutically effective amount of gilteritinib is about 115 mg. In some embodiments, the therapeutically effective amount of gilteritinib is about 120 mg. In some embodiments, the therapeutically effective amount of gilteritinib is about 125 mg. In some embodiments, the therapeutically effective amount of gilteritinib is about 130 mg. In some embodiments, the therapeutically effective amount of gilteritinib is about 135 mg. In someembodiments, the therapeutically effective amount of gilteritinib is about 140 mg. In some embodiments, the therapeutically effective amount of gilteritinib is about 145 mg. In some embodiments, the therapeutically effective amount of gilteritinib is about 150 mg.

[0151] In some embodiments, the therapeutically effective amount of midostaurin is from about50 mg to about 250 mg. In some embodiments, the therapeutically effective amount of midostaurin is about 50 mg. In some embodiments, the therapeutically effective amount of midostaurin is about 75 mg. In some embodiments, the therapeutically effective amount of midostaurin is about 100 mg. In some embodiments, the therapeutically effective amount of midostaurin is about 125 mg. In some embodiments, the therapeutically effective amount of midostaurin is about 150 mg. In some embodiments, the therapeutically effective amount of midostaurin is about 175 mg. In some embodiments, the therapeutically effective amount of midostaurin is about 200 mg. In some embodiments, the therapeutically effective amount of midostaurin is about 225 mg. In some embodiments, the therapeutically effective amount of midostaurin is about 250 mg.

[0152] In some embodiments, the therapeutically effective amount of quizartinib is from about 25 mg to about 100 mg. In some embodiments, the therapeutically effective amount of quizartinib is about 25 mg. In some embodiments, the therapeutically effective amount of quizartinib is about30 mg. In some embodiments, the therapeutically effective amount of quizartinib is about 35 mg.In some embodiments, the therapeutically effective amount of quizartinib is about 40 mg. In some embodiments, the therapeutically effective amount of quizartinib is about 45 mg. In some embodiments, the therapeutically effective amount of quizartinib is about 50 mg. In some embodiments, the therapeutically effective amount of quizartinib is about 55 mg. In some embodiments, the therapeutically effective amount of quizartinib is about 60 mg. In some embodiments, the therapeutically effective amount of quizartinib is about 65 mg. In some embodiments, the therapeutically effective amount of quizartinib is about 70 mg. In some embodiments, the therapeutically effective amount of quizartinib is about 75 mg. In some embodiments, the therapeutically effective amount of quizartinib is about 80 mg. In some embodiments, the therapeutically effective amount of quizartinib is about 85 mg. In some embodiments, the therapeutically effective amount of quizartinib is about 90 mg. In some embodiments, the therapeutically effective amount of quizartinib is about 95 mg. In some embodiments, the therapeutically effective amount of quizartinib is about 100 mg.

[0153] The pharmaceutical compositions (e g., dosage forms) described herein can be manufactured by methods well known in the art such as conventional granulating, mixing, dissolving, encapsulating, lyophilizing, or emulsifying processes, among others. The dosage forms may optionally contain one or more pharmaceutically acceptable carriers, pharmaceutically acceptable excipients and / or solvents, diluents, and other liquid vehicles, dispersion or suspension aids, surface active agents, pH modifiers, isotonic agents, thickening or emulsifying agents, stabilizers and preservatives, solid binders, lubricants and the like, as suited to the particular form desired.

[0154] In some embodiments, the one or more pharmaceutical compositions of the present disclosure are in the form of one or more a solid dosage forms. A solid dosage form is a pharmaceutical product that has a definite shape and volume. In the context of the present disclosure, a single solid dosage form contains at least one active ingredient, namely, at least elraglusib or a pharmaceutically acceptable salt thereof and / or a therapeutically effective amount of:

[0155] Oxaliplatin + Liposomal irinotecan + 5-fluorouracil (“5-FU”) + Leucovorin (NALIRIFOX);

[0156] Oxaliplatin + Irinotecan + 5-FU + Leucovorin (FOLFIRINOX);

[0157] ifosfamide;

[0158] ifosfamide and topotecan;

[0159] cyclophosphamide and topotecan;

[0160] carmustine;

[0161] procarbazine;

[0162] cytarabine;

[0163] cytarabine and daunorubicin;

[0164] gemcitabine and cisplatin;

[0165] gemcitabine, cisplatin, and at least one PARP inhibitor; or

[0166] at least one FLT3 inhibitor, as well as one or more pharmaceutically acceptable excipients suitable for inclusion in a solid dosage form. In some embodiments, the one or more solid dosage forms are a tablet, such as an immediate-release tablet, a sustained-release tablet, a controlled- release tablet, a chewable tablet, and / or a buccal or sublingual tablet. Methods for makingimmediate-release tablets, sustained-release tablets, control led-rel ease tablets, chewable tablets, and / or buccal or sublingual tablets is well known in the art.

[0167] In some embodiments, the one or more solid dosage forms are a tablet, such as an immediate-release tablet, a sustained-release tablet, a controlled-release tablet, a chewable tablet, and / or a buccal or sublingual tablet that contains at least elraglusib or a pharmaceutically acceptable salt thereof and / or a therapeutically effective amount of:

[0168] Oxaliplatin + Liposomal irinotecan + 5-fluorouracil (“5-FU”) + Leucovorin (NALIRIFOX);

[0169] Oxaliplatin + Irinotecan + 5-FU + Leucovorin (FOLFIRINOX);

[0170] ifosfamide;

[0171] ifosfamide and topotecan;

[0172] cyclophosphamide and topotecan;

[0173] carmustine;

[0174] procarbazine;

[0175] cytarabine;

[0176] cytarabine and daunorubicin;

[0177] gemcitabine and cisplatin;

[0178] gemcitabine, cisplatin, and at least one PARP inhibitor; or

[0179] at least one FLT3 inhibitor, as active ingredients, and one or more pharmaceutically acceptable excipients. In further embodiments, the one or more tablets are orally administered to a subject in need of treatment thereof, such as, for example, a subject suffering from at least one cancer.

[0180] Alternatively, the one or more solid dosage forms are a capsule, such as a hard-shelled capsule or a soft-shelled capsule. Thus, in some embodiments, the solid dosage form is a hard- shelled or soft-shelled capsule that contains at least elraglusib or a pharmaceutically acceptable salt thereof and / or a therapeutically effective amount of:

[0181] Oxaliplatin + Liposomal irinotecan + 5-fluorouracil (“5-FU”) + Leucovorin (NALIRIFOX);

[0182] Oxaliplatin + Irinotecan + 5-FU + Leucovorin (FOLFIRINOX);

[0183] ifosfamide;

[0184] ifosfamide and topotecan;

[0185] cyclophosphamide and topotecan;

[0186] carmustine;

[0187] procarbazine;

[0188] cytarabine;

[0189] cytarabine and daunorubicin;

[0190] gemcitabine and cisplatin;

[0191] gemcitabine, cisplatin, and at least one PARP inhibitor; or

[0192] at least one FLT3 inhibitor, as active ingredients, and one or more pharmaceutically acceptable excipients suitable for use in capsules. In further embodiments, the capsule is orally administered to a subject in need of treatment thereof, such as, for example, a subject suffering from at least one cancer.

[0193] In still other embodiments, the solid dosage form is in the form of a powder, bead, beadlet, granule, microparticle, nanoparticle or any combination thereof. Methods for making powders, beads, beadlets, granules, microparticles, and nanoparticles are well known in the art. Thus, in some embodiments, the one or more solid dosage forms are a powder, bead, beadlet, granule, microparticle, nanoparticle or any combination thereof that contains at least elraglusib or a pharmaceutically acceptable salt thereof and / or a therapeutically effective amount of:

[0194] Oxaliplatin + Liposomal irinotecan + 5 -fluorouracil (“5-FU”) + Leucovorin (NALIRIFOX);

[0195] Oxaliplatin + Irinotecan + 5-FU + Leucovorin (FOLFIRINOX);

[0196] ifosfamide;

[0197] ifosfamide and topotecan;

[0198] cyclophosphamide and topotecan;

[0199] carmustine;

[0200] procarbazine;

[0201] cytarabine;

[0202] cytarabine and daunorubicin;

[0203] gemcitabine and cisplatin;

[0204] gemcitabine, cisplatin, and at least one PARP inhibitor; or

[0205] at least one FLT3 inhibitor, as active ingredients, and one or more pharmaceutically acceptable excipients suitable for use in powders, beads, beadlets, granules, microparticles and nanoparticles. In further embodiments, the powder, bead, beadlet, granule, microparticle, nanoparticle, or any combination thereof is orally administered to a subject in need of treatment thereof, such as, for example, a subject suffering from at least one cancer. Additionally, in some embodiments, the powder, bead, beadlet, granule, microparticle, nanoparticle, or any combination thereof is supplied to the subject or patient in the form of a sachet.

[0206] In addition to the one or more adjuvants and / or pharmaceutically acceptable excipients, the one or more solid dosage forms formulated for oral administration as described herein can also contain one or more flavoring agents and / or coloring agents.

[0207] In still other embodiments, the one or more pharmaceutical compositions is in the form of one or more liquid dosage forms. In some aspects, the pharmaceutical composition is a single liquid dosage form. A liquid dosage form is a pharmaceutical product that is in a fluid state at room temperature. In the context of the present disclosure, a single liquid dosage form contains at least one active ingredient, namely, at least elraglusib or a pharmaceutically acceptable salt thereof and / or a therapeutically effective amount of:

[0208] Oxaliplatin + Liposomal irinotecan + 5-fluorouracil (“5-FU”) + Leucovorin (NALIRIFOX);

[0209] Oxaliplatin + Irinotecan + 5-FU + Leucovorin (FOLFIRINOX);

[0210] ifosfamide;

[0211] ifosfamide and topotecan;

[0212] cyclophosphamide and topotecan;

[0213] carmustine;

[0214] procarbazine;

[0215] cytarabine;

[0216] cytarabine and daunorubicin;

[0217] gemcitabine and cisplatin;

[0218] gemcitabine, cisplatin, and at least one PARP inhibitor; or

[0219] at least one FLT3 inhibitor, dissolved or suspended in a liquid vehicle, such as water or a mixture of water and other pharmaceutically acceptable solvents. Additionally, the liquid dosageform may also contain other adjuvants and / or pharmaceutically acceptable excipients suitable for use in such dosage forms.

[0001] In some embodiments, the one or more liquid dosage forms described herein are formulated or prepared for administration to a subject in need of treatment thereof parentally, such as by injection. For example, the one or more liquid dosage forms described herein can be formulated or prepared for administration to a subject in need of treatment such as, intravenously, intramuscularly, subcutaneously, intradermally, epidermally, or any combination thereof. Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions may be formulated according to the known art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution, suspension or emulsion in a nontoxic parenterally acceptable diluent or solvent, for example, as a solution in 1,3- butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution, U.S.P. and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose, any bland fixed oil can be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid are used in the preparation of injectables. The injectable dosage form can be sterilized, for example, by filtration through a bacterial-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable medium prior to use. Dosage forms for parenteral administration may be injected by bolus injection or by timed push or may be administered by continuous infusion.

[0002] In yet other embodiments, the one or more liquid dosage forms described herein are formulated or prepared for oral administration to a subject in need of treatment thereof in the form of a liquid, an emulsion, a microemulsion, a gel, a syrup, a slurry, a suspension, or any combination thereof. In addition to the active ingredients, the liquid dosage forms may contain inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3 -butylene glycol, cyclodextrins, dimethylformamide, oils (in particular, cottonseed, groundnut, com, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. Besides inert diluents, the dosage forms of the present disclosure can also includeadjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents.II. Methods of Treatment

[0220] Embodiments of the present disclosure relate to a method of treating a subject suffering from cancer, the method comprising the step of administering to a subject suffering from cancer one or more of the pharmaceutical composition described in Section 1. Treatment for pancreatic cancer, malignant bone tumors, soft tissue malignant tumors, brain cancer, acute myeloid leukemia (AML), or combinations thereof encompasses a multifaceted approach involving surgery, radiation therapy, and chemotherapy designed to address the cancer’s characteristics and the patient's individual health factors.

[0221] The skilled practitioner will appreciate that a subject with pancreatic cancer, malignant bone tumors, soft tissue malignant tumors, brain cancer, acute myeloid leukemia (AML), or combinations thereof can be identified based on their exhibiting or possessing one or more of the following: specific genetic markers or gene expression profiles, physical findings, laboratory test results, imaging findings, or biomarker test results associated with the development of these cancers; the presence of clinical signs related to the particular cancer; the presence of certain symptoms related to the cancer; the presence of tumor-specific markers; and other findings that indicate an individual has an increased likelihood of developing one or more of these cancers over their lifetime. Individuals at increased risk of developing these cancers may be asymptomatic and may not be experiencing any symptoms related to the disease for which they are at an elevated risk.

[0222] A subject identified as having one or more of these cancers is administered a therapeutically effective amount of one or more pharmaceutical compositions as described in Section I. In some aspects, the method involves treating a subject identified as having pancreatic cancer with a therapeutically effective amount of one or more pharmaceutical compositions described in Section I. In some aspects, the method involves treating a subject identified as having malignant bone tumors with a therapeutically effective amount of one or more pharmaceutical compositions as described in Section I. In some aspects, the method involves treating a subject identified as having soft tissue malignant tumors with a therapeutically effective amount of one or more pharmaceutical compositions described in Section I. In some aspects, the method involvestreating a subject identified as having brain cancer with a therapeutically effective amount of one or more pharmaceutical compositions described in Section I. In some aspects, the method involves treating a subject identified as having acute myeloid leukemia (AML) with a therapeutically effective amount of one or more pharmaceutical compositions described in Section I.

[0223] In some aspects, the method involves treating a subject identified as having osteosarcoma with a therapeutically effective amount of one or more pharmaceutical compositions described in Section I. In some aspects, the method involves treating a subject identified as having Ewing sarcoma with a therapeutically effective amount of one or more pharmaceutical compositions described in Section I. In some aspects, the method involves treating a subject identified as having chondrosarcoma with a therapeutically effective amount of one or more pharmaceutical compositions described in Section I. In some aspects, the method involves treating a subject identified as having liposarcoma with a therapeutically effective amount of one or more pharmaceutical compositions described in Section I. In some aspects, the method involves treating a subject identified as having leiomyosarcoma with a therapeutically effective amount of one or more pharmaceutical compositions described in Section I. In some aspects, the method involves treating a subject identified as having undifferentiated pleomorphic sarcoma with a therapeutically effective amount of one or more pharmaceutical compositions described in Section I. In some aspects, the method involves treating a subject identified as having synovial sarcoma with a therapeutically effective amount of one or more pharmaceutical compositions described in Section I. In some aspects, the method involves treating a subject identified as having malignant peripheral nerve sheath tumor (MPNST) with a therapeutically effective amount of one or more pharmaceutical compositions described in Section I.

[0224] In some aspects, the method involves treating a subject identified as having primary malignant tumor with a therapeutically effective amount of one or more pharmaceutical compositions described in Section I. In some aspects, the method involves treating a subject identified as having brain metastatic malignant tumor with a therapeutically effective amount of one or more pharmaceutical compositions described in Section I.

[0225] In some aspects, the method involves treating a subject identified as having glioma with a therapeutically effective amount of one or more pharmaceutical compositions described in Section I. In some aspects, the method involves treating a subject identified as having medulloblastoma, central nervous system lymphoma, with a therapeutically effective amount ofone or more pharmaceutical compositions described in Section I. In some aspects, the method involves treating a subject identified as having central nervous system lymphoma with a therapeutically effective amount of one or more pharmaceutical compositions described in Section I.

[0226] In some aspects, the method involves treating a subject identified as having metastatic malignant tumor originated from melanoma with a therapeutically effective amount of one or more pharmaceutical compositions described in Section I. In some aspects, the method involves treating a subject identified as having metastatic malignant tumor originated from breast cancer with a therapeutically effective amount of one or more pharmaceutical compositions described in Section I. In some aspects, the method involves treating a subject identified as having metastatic malignant tumor originated from lung cancer with a therapeutically effective amount of one or more pharmaceutical compositions described in Section I. In some aspects, the method involves treating a subject identified as having metastatic malignant tumor originated from colorectal cancer with a therapeutically effective amount of one or more pharmaceutical compositions described in Section I. In some aspects, the method involves treating a subject identified as having metastatic malignant tumor originated from kidney cancer with a therapeutically effective amount of one or more pharmaceutical compositions described in Section I.

[0227] Individuals at increased risk for the development of pancreatic cancer, malignant bone tumors, soft tissue malignant tumors, brain cancer, acute myeloid leukemia (AML), or combinations thereof may be diagnosed based on presenting symptoms, physical findings, laboratory test results, imaging results, and other indicators that collectively meet diagnostic criteria for these cancers. In exemplary embodiments, such individuals exhibit specific laboratory findings, physical symptoms, or imaging results that place them at heightened risk of developing one or more of these cancers. In some embodiments, individuals with or at risk for these cancers may show increased or decreased expression levels of particular cancer-associated genes, specific protein markers, metabolic markers, or other relevant biomarkers. Methods described herein may include identifying and treating individuals at increased risk for developing these cancers. Prior to confirming a diagnosis or assessing elevated risk, the individual may undergo screening for one or more cancer-related biomarkers, including but not limited to gene expression levels, to assess potential risk factors. Individuals selected for screening may have a suspected predisposition to cancer development, such as a familial history of cancer or specific gene mutations associated withcancer susceptibility. The skilled artisan will appreciate that the screening of a subject suspected of having one or more of these cancers involves evaluating various patient-specific factors to enhance overall prognosis data.

[0228] In exemplary embodiments, a subject may be screened for pancreatic cancer, malignant bone tumors, soft tissue malignant tumors, brain cancer, acute myeloid leukemia (AML), or any combination thereof. Screening for these conditions may begin at various ages depending on individual risk factors. In exemplary embodiments, symptoms such as unexplained weight loss, persistent fatigue, chronic pain localized to bones or soft tissues, neurological changes (such as persistent headaches, seizures, or cognitive difficulties), abnormal blood counts, or masses detectable by physical examination or imaging may prompt further diagnostic evaluation. In exemplary embodiments, the subject is a mammal. In exemplary embodiments, the subject is a non-human mammal. In exemplary embodiments, the subject is a human.

[0229] In some embodiments of the above method, the cancer is pancreatic cancer, malignant bone tumors, soft tissue malignant tumors, brain cancer, acute myeloid leukemia (AML) or any combinations thereof.

[0230] In some embodiments of the above method, the cancer is pancreatic cancer. In some embodiments of the above method, the cancer is malignant bone tumors. In some embodiments of the above method, the cancer is soft tissue malignant tumors. In some embodiments of the above method, the cancer is brain cancer. In some embodiments of the above method, the cancer is acute myeloid leukemia (AML).

[0231] In some embodiments of the above method, the malignant bone tumor is osteosarcoma, Ewing sarcoma, chondrosarcoma, or combinations thereof.

[0232] In some embodiments of the above method, the malignant bone tumor is osteosarcoma. In some embodiments of the above method, the malignant bone tumor is Ewing sarcoma. In some embodiments of the above method, the malignant bone tumor is chondrosarcoma.

[0233] In some embodiments of the above method, the soft tissue malignant tumor is liposarcoma, leiomyosarcoma, undifferentiated pleomorphic sarcoma, synovial sarcoma, malignant peripheral nerve sheath tumor (MPNST), or combinations thereof.

[0234] In some embodiments of the above method, the soft tissue malignant tumor is liposarcoma. In some embodiments of the above method, the soft tissue malignant tumor is leiomyosarcoma. In some embodiments of the above method, the soft tissue malignant tumor isundifferentiated pleomorphic sarcoma. In some embodiments of the above method, the soft tissue malignant tumor is synovial sarcoma. In some embodiments of the above method, the soft tissue malignant tumor is malignant peripheral nerve sheath tumor (MPNST).

[0235] In some embodiments of the above method, the brain cancer is a primary malignant tumor, a brain metastatic malignant tumor, or a combination thereof.

[0236] In some embodiments of the above method, the brain cancer is a primary malignant tumor. In some embodiments of the above method, the brain cancer is a brain metastatic malignant tumor.

[0237] In some embodiments of the above method, the primary malignant tumor is a glioma, medulloblastoma, central nervous system lymphoma, or combination thereof.

[0238] In some embodiments of the above method, the primary malignant tumor is a glioma. In some embodiments of the above method, the primary malignant tumor is medulloblastoma. In some embodiments of the above method, the primary malignant tumor is a central nervous system lymphoma.

[0239] In some embodiments of the above method, the metastatic malignant tumor originated from melanoma, breast cancer, lung cancer, colorectal cancer, kidney cancer, or any combination thereof.

[0240] In some embodiments of the above method, the metastatic malignant tumor originated from melanoma. In some embodiments of the above method, the metastatic malignant tumor originated from breast cancer. In some embodiments of the above method, the metastatic malignant tumor originated from lung cancer. In some embodiments of the above method, the metastatic malignant tumor originated from colorectal cancer. In some embodiments of the above method, the metastatic malignant tumor originated from kidney cancer.

[0241] Certain aspects of the presently disclosed subject matter having been stated herein above, which are addressed in whole or in part by the presently disclosed subject matter, other aspects will become evident as the description proceeds when taken in connection with the accompanying Examples as best described herein below.EXAMPLES

[0242] The following Examples have been included to provide guidance to one of ordinary skill in the art for practicing representative embodiments of the presently disclosed subject matter. In light of the present disclosure and the general level of skill in the art, those of skill can appreciate that the following Examples are intended to be exemplary only and that numerous changes,modifications, and alterations can be employed without departing from the scope of the presently disclosed subject matter. The synthetic descriptions and specific examples that follow are only intended for the purposes of illustration and are not to be construed as limiting in any manner to make compounds of the disclosure by other methods.EXAMPLE 1Immune modulation and inhibition of immune evasion[00243J GSK-3P plays an important role in immune cell function, as inhibition of GSK-30 can facilitate immune cell expansion, differentiation and activation including T and natural killer (NK) cells. GSK-3P inhibition increases the ability of effector T cells to kill tumors in vivo through the induction of effector proteins granzyme B and FasL in gastric cancer models. Additionally, inhibition of GSK-3, with both small molecules and small interfering RNA (siRNA), downregulates programmed cell death protein 1 (PD-1) expression in CD8 and cytolytic T cells and enhances their function. GSK-3P inhibition also lowers PD-1 expression and promotes longterm survival and generation of memory CAR-T cells in vivo. These memory T-cells enabled 100% clearance of cancer cells after rechallenging during tumor remission. Recently, inhibition of GSK-3P with small molecules was shown to reduce the expression of T cell immunoreceptor with immunoglobulin and ITEM domain (TIGIT) and lymphocyte activation gene-3 (LAG-3), additional immune system suppressing molecules that work in concert with PDL-1 to reduce antitumor surveillance by the system, another inhibitory receptor, LAG-3. Combining GSK-3P inhibition and LAG-3 blockade significantly enhanced clearance of melanoma tumors compared to either treatment alone.

[0244] Blocking GSK-3 in NK cells leads to enrichment of mature NK cells and primes them for enhanced cytokine production and anti -turn or function in vivo. GSK-3 P expression was increased in the NK cells of patients with acute myeloid leukemia (AML) and inhibition of GSK-3P led to increased cell directed cytotoxicity in these patient-derived samples. Inhibition of GSK-3 also decreased LAG-3 expression on NK cells. GSK-3P activity has also been tied to transforming growth factor p (TGFP) expression. TGFp released by cancer cells, stromal fibroblasts and other cells in the tumor microenvironment further promotes cancer progression by shaping the architecture of the tumor and by suppressing the antitumor activities of immune cells, thus generating an immunosuppressive environment that prevents or attenuates the efficacy ofanticancer immunotherapies. Therefore, blocking GSK-3P may reduce TGFP-mediated immunosuppression.

[0245] Elraglusib has now been demonstrated to decrease expression of PD-1, TIGIT and LAG- 3 and to enhance the anti-tumor effects of anti -PD-1 checkpoint inhibition in animal tumor models. Thus, elraglusib blockade of GSK-3P activity may improve immune response to tumors by augmenting the responsiveness of a patient’s immune system in addition to the direct anti -tumor effects of elraglusib within the cancer cells themselves.EXAMPLE 2Inhibition of cell proliferation

[0246] Inhibition of GSK-3P leads to inhibition of tumor cell proliferation. This has been shown in multiple tumor model systems using elraglusib. A number of pathways have been implicated in the inhibition of cell proliferation mediated by GSK-3 inhibitors including MYC, Cyclin DI, TGFa, epidermal growth factor receptor, Ras, PI3K / Akt, and NF-KB. Given GSK-3 ’s role as an adapter of multiple signaling pathways, elraglusib may exert its antiproliferative effects through the inhibition of one or more of these pathways.EXAMPLE 3Reduced tumor fibrosis and decreased immune evasion

[0247] A chronic inflammatory microenvironment is conducive to tumorigenesis (e.g., pancreatitis patients are known to have increased risk of pancreatic cancer) and tumors can undergo epithelial to mesenchymal transition (EMT), leading to increased metastasis, under inflammatory conditions. Moreover, several profibrotic cytokines (e.g., TGF-0, TNF-a and IL-1) secreted by inflammatory and tumor cells converge to activate pathways that regulate EMT. Further, GSK-3 has also been demonstrated to be a mediator of epithelial-mesenchymal transitions. Therefore, the inflammatory response designed to fight tumor progression also ends up promoting metastasis and tumor-associated fibrosis. Tumor fibrosis presents multiple challenges to drug delivery and tumor immune recognition and contributes to drug resistance by presenting physical barriers in the tumor microenvironment to drug and immune cell access. Elraglusib has been shown to reduce the inflammation and signaling that contribute to immune system evasion in multiple animal models, including lung and liver, of fibrosis suggesting another mechanism through which elraglusib may interfere in cancer growth.EXAMPLE 4Increased apoptosis

[0248] GSK-3 supports the resistance of cancer cells to apoptosis. A number of studies have suggested that the primary mechanism of GSK-3 -mediated prevention of apoptosis in cancer cells is through the NF-KB pathway. Apoptosis is a mechanism of cell death that is often suppressed in cancer cells leading to cancer cell survival and resistance even after treatment with chemotherapeutic drugs or radiation. Studies have shown that eliminating or inhibiting GSK-3P in cancer cells is able to restore apoptosis to cells, leading to tumor cell death. These findings support GSK-30 as a potential therapeutic target to potentiate apoptosis in cancer cells.

[0249] In addition to GSK-3[3’s role in regulating NF-KB activity, it has also been shown to modulate DNA damage repair (DDR) pathways. DDR pathways are integral in both normal and cancer cells to maintain genomic integrity by sensing and responding to DNA damage. In normal cells, DDR helps to identify and repair mutations or breaks in DNA and restore the normal, intact sequence. If the cell is unable to repair a DNA lesion, these DDR pathways can then initiate cell death signaling to prevent neoplastic growth. In cancer, DNA repair has been subverted to protect tumor cells from repairing DNA damage that would otherwise lead to spontaneous apoptosis. Cancers will often have mutations in at least one DNA repair pathways leading to dysregulated cell growth and replication. Elraglusib inhibition of GSK-3P has been shown to sensitize pancreatic cancer cells to gemcitabine by disrupting TopBPl / ATR mediated cell-cycle arrest and DNA repair. GSK-30’s emerging role in regulating DDR pathways supports its use in combination with DNA damaging chemotherapy.

[0250] Inhibition of DDR pathways have also been shown to enhance tumor immune recognition by immune checkpoint inhibitors such as anti-PD-1, creating neoantigens in tumors that lead to recruitment of tumor infiltrating immune cells, decreased immune evasion and increased antitumor immune response. This provides the link that couples the various elraglusib-related mechanisms of action through the targeting of GSK-3.EXAMPLE 5Development of Elraglusib for the Treatment of Ewing Sarcoma

[0251] An estimated 9,620 children (ages 0-14 years) and 5,280 adolescents (ages 15-19 years) are expected to be diagnosed with cancer in the United States in 2024. It is also estimated that 1,040 children and 550 adolescents will die from the disease in the United States in 2024.Additionally, approximately 40% of childhood cancer survivors have severe, life-threatening or fatal complications within 30 years of diagnosis and up to 90% of survivors will have a chronic health condition by the age of 45. These long-term effects are related to the type of treatment used such as chemotherapy and radiation which can have a material adverse impact on developing organs.

[0252] Extensive preclinical work in pediatric malignancies has demonstrated strong synergy between elraglusib and standard-of-care chemotherapy in neuroblastoma, sarcoma, glioma, and other cancers. Building on these findings, a study was initiated to evaluate the safety of elraglusib, with or without chemotherapy, in pediatric patients with refractory malignancies. The dose escalation part of the study assigned patients to elraglusib alone, elraglusib / irinotecan or elraglusib / cyclophosphamide and topotecan (CT). The recommended dosage was confirmed as 15 mg / kg twice weekly and additional patients were added to the elraglusib / irinotecan or elraglusib / CT to explore initial signals of anticancer activity. Thirty-six patients had been enrolled and received at least one dose of elraglusib. No serious adverse events were observed with elraglusib monotherapy at the first two dose levels. Six patients (26.1%) achieved stable disease and a patient with refractory, metastatic Ewing sarcoma had a radiographic and pathologic complete response (CR) after 3 cycles of elraglusib / CT. Recently, a second CR was observed in a five-year-old boy with treatment resistant neuroblastoma that had completed nine cycles of elraglusib in combination with CT. Based on the response from the Ewing sarcoma patient, additional patients with metastatic, refractory Ewing and Ewing-like sarcoma were enrolled in the elraglusib / CT arm.

[0253] Six Ewing sarcoma patients and one patient with a desmoplastic small round cell tumor (DSRCT) were enrolled in the 1902 trial had metastatic disease and disease progression prior to joining the study despite previous chemotherapy and radiation (4 / 7 patients had received two or more previous chemotherapy regimens). There are currently no known treatment regimens that meaningfully extend life in Ewing sarcoma patients with metastatic, refractory disease. All patients received the combination of elraglusib and cyclophosphamide / topotecan. The Ewing sarcoma patient with the CR described above stopped all treatments after 4 months to return to school and continues to be in complete remission with no evidence of disease almost 2 years after termination of treatment. A second Ewing sarcoma patient had a CMR (Complete Metabolic Response) with no detectable lesions by FDG-PET, and a DSRCT patient had a partial response with 52%reduction in tumor. Two additional Ewing sarcoma patients have stable disease as the best overall response, one patient had progressive disease, and one patient withdrew from treatment prior to evaluation of response. Four (4 / 7) patients remain alive and three continue on treatment.

[0254] The five-year survival rate for patients with recurrent (relapsed) Ewing sarcoma is less than 30%. Refractory patients with metastasis and disease progression, despite undergoing two or more chemotherapy regimens, face a very short survival period of 3-8 months. No treatment regimens currently offer meaningful life extension for patients with metastatic, refractory Ewing sarcoma. The primary endpoint is overall response rate (ORR), with an initial efficacy readout expected approximately 12-18 months after commencement.INCORPORATION BY REFERENCE

[0255] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference in their entireties to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference in its entirety. In case of conflict, the present application, including any definitions herein, will control.

[0256] The present disclosure has multiple aspects, illustrated by the non-limiting examples described herein.

[0257] It is understood that the foregoing detailed description and accompanying examples are merely illustrative and are not to be taken as limitations upon the scope of the disclosure, which is defined solely by the appended claims and their equivalents.

[0258] Various changes and modifications to the disclosed embodiments will be apparent to those skilled in the art. Such changes and modifications, including without limitation those relating to the chemical structures, substituents, derivatives, intermediates, syntheses, compositions, formulations, or methods of use of the disclosure, may be made without departing from the spirit and scope thereof.

[0259] For reasons of completeness, various aspects of the disclosure are set out in the following numbered clauses:

[0260] Clause 1. A pharmaceutical composition comprising: a combination of a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of:(a) Oxaliplatin + Liposomal irinotecan + 5-FU + Leucovorin (NALIRIFOX);(a) Oxaliplatin + Irinotecan + 5-FU + Leucovorin (FOLFIRINOX);(b) ifosfamide;(c) ifosfamide and topotecan;(d) cyclophosphamide and topotecan;(e) carmustine;(f) procarbazine;(g) cytarabine;(h) cytarabine and daunorubicin;(i) gemcitabine and cisplatin;(j) gemcitabine, cisplatin and at least one PARP inhibitor; and(k) at least one FLT3 inhibitor, wherein the combination is formulated for simultaneous, sequential, and / or separate administration, and for is suitable for oral administration, intrathecal administration and / or intravenous administration subject.

[0261] Clause 2. The pharmaceutical composition of clause 1, wherein the pharmaceutical composition is suitable for oral administration.

[0262] Clause 3. The pharmaceutical composition of clause 2, wherein the pharmaceutical composition is a solid dosage form.

[0263] Clause 4. The pharmaceutical composition of clause 3, wherein the solid dosage form is a capsule or tablet.

[0264] Clause 5. The pharmaceutical composition of clause 1, wherein the pharmaceutical composition is suitable for intravenous injection.

[0265] Clause 6. The pharmaceutical composition of clause 1, wherein the pharmaceutical composition is suitable for intrathecal injection.

[0266] Clause 7. The pharmaceutical composition of any of clauses 1 to 6, wherein the pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of NALIRIFOX.

[0267] Clause 8. The pharmaceutical composition of any of clauses 1 to 6, wherein the pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of FOLFIRINOX.

[0268] Clause 9. The pharmaceutical composition of any of clauses 1 to 6, wherein the pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of ifosfamide.

[0269] Clause 10. The pharmaceutical composition of any of clauses 1 to 6, wherein the pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof, a therapeutically effective amount of ifosfamide and a therapeutically effective amount of topotecan.

[0270] Clause 11. The pharmaceutical composition of any of clauses 1 to 6, wherein the pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of cyclophosphamide and a therapeutically effective amount of topotecan.

[0271] Clause 12. The pharmaceutical composition of any of clauses 1 to 6, wherein the pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of carmustine.

[0272] Clause 13. The pharmaceutical composition of any of clauses 1 to 6, wherein the pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of procarbazine.

[0273] Clause 14. The pharmaceutical composition of any of clauses 1 to 6, wherein the pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of cytarabine.

[0274] Clause 15. The pharmaceutical composition of any of clauses 1 to 6, wherein the pharmaceutical composition comprises a therapeutically effective amount of elraglusib or apharmaceutically acceptable salt thereof and a therapeutically effective amount of cytarabine and a therapeutically effective amount of daunorubicin.

[0275] Clause 16. The pharmaceutical composition of any of clauses 1 to 6, wherein the pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of gemcitabine and a therapeutically effective amount of cisplatin.

[0276] Clause 17. The pharmaceutical composition of any of clauses 1 to 6, wherein the pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of gemcitabine, a therapeutically effective amount of cisplatin, and a therapeutically effective amount at least one PARP inhibitor.

[0277] Clause 18. The pharmaceutical composition of any of clauses 1 to 6, wherein the at least one PARP inhibitor is olaparib, talazoparib, rucaparib, niraparib or any combination thereof.

[0278] Clause 19. The pharmaceutical composition of any of clauses 1 to 6, wherein the pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of at least one FLT3 inhibitor.

[0279] Clause 20. The pharmaceutical composition of any of clauses 1 to 6, wherein the at least one FLT3 inhibitor is gilteritinib, midostaurin, quizartinib, or any combination thereof.

[0280] Clause 21. The pharmaceutical composition of any of clauses 1 to 20, wherein the therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof is from about 5 mg / kg to about 50 mg / kg.

[0281] Clause 22. The pharmaceutical composition of any of clauses 1 to 21, wherein the therapeutically effective amount of NALIRIFOX is from about 40 mg / m2to about 2400 mg / m2.

[0282] Clause 23. The pharmaceutical composition of any of clauses 1 to 22, wherein the therapeutically effective amount of FOLFIRINOX is from about 40 mg / m2to about 2400 mg / m2.

[0283] Clause 24. The pharmaceutical composition of any of clauses 1 to 20, wherein the therapeutically effective amount of ifosfamide is from about 0.5 g / m2to about 5 g / m2

[0284] Clause 25. The pharmaceutical composition of any of clauses 1 to 21, wherein the therapeutically effective amount of cyclophosphamide is from about 1 mg / kg to about 75 mg / kg.

[0285] Clause 26. The pharmaceutical composition of any of clauses 1 to 22, wherein the therapeutically effective amount of topotecan is from about 0.5 mg / m2to about 3 mg / m2.

[0286] Clause 27. The pharmaceutical composition of any of clauses 1 to 25, wherein the therapeutically effective amount of carmustine is from about 50 mg / m2to about 1 g / m2.

[0287] Clause 28. The pharmaceutical composition of any of clauses 1 to 26, wherein the therapeutically effective amount of procarbazine is from about 1 mg / kg to about 10 mg / kg.

[0288] Clause 29. The pharmaceutical composition of any of clauses 1 to 30, wherein the therapeutically effective amount of cytarabine is from about 1 mg / m2to about 5 g / m2.

[0289] Clause 30. The pharmaceutical composition of any of clauses 1 to 31, wherein the therapeutically effective amount of daunorubicin is from about 40 mg / m2to about 900 mg / m2.

[0290] Clause 31. The pharmaceutical composition of clause 17, wherein the therapeutically effective amount of olaparib is from about 300 mg to about 600 mg.

[0291] Clause 32. The pharmaceutical composition of clause 17, wherein the therapeutically effective amount of talazoparib is from about 0.1 mg to about 2 mg.

[0292] Clause 33. The pharmaceutical composition of clause 17, wherein the therapeutically effective amount of rucaparib is from about 200 mg to about 600 mg.

[0293] Clause 34. The pharmaceutical composition of clause 17, wherein the therapeutically effective amount of niraparib is from about 200 mg to about 400 mg.

[0294] Clause 35. The pharmaceutical composition of clause 17, wherein the therapeutically effective amount of gilteritinib is from about 20 mg to about 150 mg.

[0295] Clause 36. The pharmaceutical composition of clause 17, wherein the therapeutically effective amount of midostaurin is from about 50 mg to about 250 mg.

[0296] Clause 37. The pharmaceutical composition of clause 17, wherein the therapeutically effective amount of quizartinib is from about 25 mg to about 100 mg.

[0297] Clause 38. The pharmaceutical composition of any of clauses 1 to 30, wherein the pharmaceutical composition further comprises one or more pharmaceutically acceptable excipients.

[0298] Clause 39. A method of treating a subject suffering from cancer, the method comprising the step of administering to a subject suffering from cancer a pharmaceutical composition of any of clauses 1-31.

[0299] Clause 40. The method of clause 32, wherein the cancer is pancreatic cancer, malignant bone tumors, soft tissue malignant tumors, brain cancer, acute myeloid leukemia (AML) or any combinations thereof.

[0300] Clause 41. The method of clause 33, wherein the malignant bone tumor is osteosarcoma, Ewing sarcoma, chondrosarcoma, or combinations thereof.

[0301] Clause 42. The method of clause 33, wherein the soft tissue malignant tumor is liposarcoma, leiomyosarcoma, undifferentiated pleomorphic sarcoma, synovial sarcoma, malignant peripheral nerve sheath tumor (MPNST), or combinations thereof.

[0302] Clause 43. The method of clause 33, wherein the brain cancer is a primary malignant tumor, a brain metastatic malignant tumor, or a combination thereof.

[0303] Clause 44. The method of clause 36, wherein the primary malignant tumor is a glioma, medulloblastoma, central nervous system lymphoma, or combination thereof.

[0304] Clause 45. The method of clause 36, wherein the metastatic malignant tumor originated from melanoma, breast cancer, lung cancer, colorectal cancer, kidney cancer, or any combination thereof.REFERENCES

[0305] All publications, patent applications, patents, and other references mentioned in the specification are indicative of the level of those skilled in the an to which the presently disclosed subject matter pertains. All publications, patent applications, patents, and other references are herein incorporated by reference to the same extent as if each individual publication, patent application, patent, and other reference was specifically and individually indicated to be incorporated by reference. It will be understood that, although a number of patent applications,patents, and other references are referred to herein, such reference does not constitute an admission that any of these documents form part of the common general knowledge in the art,

[0306] Although the foregoing subject matter has been described in some detail by way of illustration and example for purposes of clarity of understanding, it will be understood by those skilled in the art that certain changes and modifications can be practiced within the scope of the appended claims.

[0307] Bilim V, Ougolkov A, Yuuki K, Naito S, Kawazoe H, Muto A, Oya M, Billadeau D, Motoyama T, Tomita Y. Glycogen synthase kinase-3: a new therapeutic target in renal cell carcinoma. Br J Cancer. 2009; 101(12):2005-14. doi: 10.1038 / sj .bjc.6605437.

[0308] Form S-l. Filed with the Securities and Exchange Comission on May 24, 2024. https: / / www.sec.gov / edgar / browse / 7CIK 652935

[0309] Hilliard TS, Gaisina IN, Muehlbauer AG, Gaisin AM, Gallier F, Burdette FE. Glycogen synthase kinase 3beta inhibitors induce apoptosis in ovarian cancer cells and inhibit in-vivo tumor growth. Anticancer Drugs. 2011 ;22(10):978-85. doi: 10.1097 / CAD.0b013e32834ac8fc.

[0310] Ougolkov AV, Fernandez-Zapico ME, Bilim VN, Smyrk TC, Chari ST, Billadeau DD. Aberrant nuclear accumulation of glycogen synthase kinase-3beta in human pancreatic cancer: association with kinase activity and tumor dedifferentiation. Clin Cancer Res. 2006;12(17):5074- 81.

[0311] Ougolkov AV, Bone ND, Fernandez-Zapico ME, Kay NE, Billadeau DD. Inhibition of Glycogen Synthase Kinase-3 activity leads to epigenetic silencing of nuclear factor kappaB target genes and induction of apoptosis in chronic lymphocytic leukemia B cells. Blood. 2007; 110(2):735-42. doi: 10.1182 / blood-2006- 12-060947.

[0312] Pathak et al. FOLFIRINOX with glycogen synthase kinase-3 beta (GSK-3P) inhibitor elraglusib and transforming growth factor- (TGFP) inhibitor losartan in untreated metastatic pancreatic ductal adenocarcinoma (PDAC): interim analysis of safety cohort. Cancer Res. 2024;84(17) Suppl: C073. Presented as a poster at the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research on Sept 18, 2024.

[0313] Ugolkov A, Qiang W, Bondarenko G, Procissi D, Gaisina I, James CD, Chandler J, Kozikowski A, Gunosewoyo H, O'Halloran T, Raizer J, Mazar AP. Combination treatment with the GSK-3 inhibitor 9-ING-41 and CCNU cures orthotopic chemoresistant glioblastoma in patient- derived xenograft models. Transl Oncol. 2017;10(4):669-678. doi: 10.1016 / j.tranon.2017.06.003.

[0314] Ugolkov AV, Matsangou M, Taxter TJ, O'Halloran TV, Cryns VL, Giles FJ, Mazar AP. Aberrantexpression of glycogen synthase kinase-3p in human breast and head and neck cancer. Oncol Lett. 2018;16(5):6437-44. doi: 10.3892 / ol.2018.9483.

[0315] Ugolkov AV, Bondarenko GI, Dubrovskyi O, Berbegall AP, Navarro S, Noguera R, O'Halloran TV, Hendrix MJ, Giles FJ, Mazar AP. 9-ING-41, a small-molecule glycogen synthase kinase-3 inhibitor, is active in neuroblastoma. Anticancer Drugs. 2018;29(8):717-724. doi: 10.1097 / CAD.0000000000000652.

[0316] Walz A, Ugolkov A, Chandra S, Kozikowski A, Carneiro BA, O'Halloran TV, Giles FJ, Billadeau DD, Mazar AP. Molecular pathways: revisiting glycogen synthase kinase-3beta as a target for the treatment of cancer. Clin Cancer Res. 2017;23(8): 1891-7. doi: 10.1158 / 1078-0432. CCR-15-2240.

[0317] Wang Z, Smith KS, Murphy M, Piloto O, Somervaille TC, Cleary ML. Glycogen synthase kinase 3 in MLL leukaemia maintenance and targeted therapy. Nature. 2008;455(7217): 1205-9. doi: 10.1038 / nature07284.

Claims

THAT WHICH IS CLAIMED:

1. A pharmaceutical composition comprising: a combination of a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of: a) Oxaliplatin + Liposomal irinotecan + 5-FU + Leucovorin (NALIRIFOX); b) Oxaliplatin + Irinotecan + 5-FU + Leucovorin (FOLFIRINOX); c) ifosfamide; d) ifosfamide and topotecan; e) cyclophosphamide and topotecan; f) carmustine; g) procarbazine; h) cytarabine; i) cytarabine and daunorubicin; j) gemcitabine and cisplatin; k) gemcitabine, cisplatin and at least one PARP inhibitor; and l) at least one FLT3 inhibitor, wherein the combination is formulated for simultaneous, sequential, and / or separate administration, and for is suitable for oral administration, intrathecal administration and / or intravenous administration subject.

2. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is suitable for oral administration.

3. The pharmaceutical composition of claim 2, wherein the pharmaceutical composition is a solid dosage form.

4. The pharmaceutical composition of claim 3, wherein the solid dosage form is a capsule or tablet.

5. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is suitable for intravenous injection.

6. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is suitable for intrathecal injection.

7. The pharmaceutical composition of any of claims 1 to 6, wherein the pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of NALIRIFOX.

8. The pharmaceutical composition of any of claims 1 to 6, wherein the pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of FOLFIRINOX.

9. The pharmaceutical composition of any of claims 1 to 6, wherein the pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of ifosfamide.

10. The pharmaceutical composition of any of claims 1 to 6, wherein the pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof, a therapeutically effective amount of ifosfamide and a therapeutically effective amount of topotecan.

11. The pharmaceutical composition of any of claims 1 to 6, wherein the pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of cyclophosphamide and a therapeutically effective amount of topotecan.

12. The pharmaceutical composition of any of claims 1 to 6, wherein the pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of carmustine.

13. The pharmaceutical composition of any of claims 1 to 6, wherein the pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of procarbazine.

14. The pharmaceutical composition of any of claims 1 to 6, wherein the pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of cytarabine.

15. The pharmaceutical composition of any of claims 1 to 6, wherein the pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of cytarabine and a therapeutically effective amount of daunorubicin.

16. The pharmaceutical composition of any of claims 1 to 6, wherein the pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of gemcitabine and a therapeutically effective amount of cisplatin.

17. The pharmaceutical composition of any of claims 1 to 6, wherein the pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of gemcitabine, a therapeutically effective amount of cisplatin, and a therapeutically effective amount at least one PARP inhibitor.

18. The pharmaceutical composition of any of claims 1 to 6, wherein the at least one PARP inhibitor is olaparib, talazoparib, rucaparib, niraparib or any combination thereof.

19. The pharmaceutical composition of any of claims 1 to 6, wherein the pharmaceutical composition comprises a therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of at least one FLT3 inhibitor.

20. The pharmaceutical composition of any of claims 1 to 6, wherein the at least one FLT3 inhibitor is gilteritinib, midostaurin, quizartinib, or any combination thereof.

21. The pharmaceutical composition of any of claims 1 to 20, wherein the therapeutically effective amount of elraglusib or a pharmaceutically acceptable salt thereof is from about 5 mg / kg to about 50 mg / kg.

22. The pharmaceutical composition of any of claims 1 to 21, wherein the therapeutically effective amount of NALIRIFOX is from about 40 mg / m2to about 2400 mg / m2.

23. The pharmaceutical composition of any of claims 1 to 22, wherein the therapeutically effective amount of FOLFZRINOX is from about 40 mg / m2to about 2400 mg / m2.

24. The pharmaceutical composition of any of claims 1 to 20, wherein the therapeutically effective amount of ifosfamide is from about 0.5 g / m2to about 5 g / m2.

25. The pharmaceutical composition of any of claims 1 to 21, wherein the therapeutically effective amount of cyclophosphamide is from about 1 mg / kg to about 75 mg / kg.

26. The pharmaceutical composition of any of claims 1 to 22, wherein the therapeutically effective amount of topotecan is from about 0.5 mg / m2to about 3 mg / m2.

27. The pharmaceutical composition of any of claims 1 to 25, wherein the therapeutically effective amount of carmustine is from about 50 mg / m2to about 1 g / m2.

28. The pharmaceutical composition of any of claims 1 to 26, wherein the therapeutically effective amount of procarbazine is from about 1 mg / kg to about 10 mg / kg.

29. The pharmaceutical composition of any of claims 1 to 30, wherein the therapeutically effective amount of cytarabine is from about 1 mg / m2to about 5 g / m230. The pharmaceutical composition of any of claims 1 to 31, wherein the therapeutically effective amount of daunorubicin is from about 40 mg / m2to about 900 mg / m2.

31. The pharmaceutical composition of claim 17, wherein the therapeutically effective amount of olaparib is from about 300 mg to about 600 mg.

32. The pharmaceutical composition of claim 17, wherein the therapeutically effective amount of talazoparib is from about 0.1 mg to about 2 mg.

33. The pharmaceutical composition of claim 17, wherein the therapeutically effective amount of rucaparib is from about 200 mg to about 600 mg.

34. The pharmaceutical composition of claim 17, wherein the therapeutically effective amount of niraparib is from about 200 mg to about 400 mg.

35. The pharmaceutical composition of claim 17, wherein the therapeutically effective amount of gilteritinib is from about 20 mg to about 150 mg.

36. The pharmaceutical composition of claim 17, wherein the therapeutically effective amount of midostaurin is from about 50 mg to about 250 mg.

37. The pharmaceutical composition of claim 17, wherein the therapeutically effective amount of quizartinib is from about 25 mg to about 100 mg.

38. The pharmaceutical composition of any of claims 1 to 30, wherein the pharmaceutical composition further comprises one or more pharmaceutically acceptable excipients.

39. A method of treating a subject suffering from cancer, the method comprising the step of administering to a subject suffering from cancer a pharmaceutical composition of any of claims 1-31.

40. The method of claim 32, wherein the cancer is pancreatic cancer, malignant bone tumors, soft tissue malignant tumors, brain cancer, acute myeloid leukemia (AML) or any combinations thereof.

41. The method of claim 33, wherein the malignant bone tumor is osteosarcoma, Ewing sarcoma, chondrosarcoma, or combinations thereof.

42. The method of claim 33, wherein the soft tissue malignant tumor is liposarcoma, leiomyosarcoma, undifferentiated pleomorphic sarcoma, synovial sarcoma, malignant peripheral nerve sheath tumor (MPNST), or combinations thereof.

43. The method of claim 33, wherein the brain cancer is a primary malignant tumor, a brain metastatic malignant tumor, or a combination thereof.

44. The method of claim 36, wherein the primary malignant tumor is a glioma, medulloblastoma, central nervous system lymphoma, or combination thereof.

45. The method of claim 36, wherein the metastatic malignant tumor originated from melanoma, breast cancer, lung cancer, colorectal cancer, kidney cancer, or any combination thereof.

Images