APILIMOD FOR USE IN THE TREATMENT OF COLORECTAL CANCER
The present invention relates to methods for treating colorectal cancer with apilimod and related compositions and methods.
1 . A method for treating colorectal cancer in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of apilimod, or a pharmaceutically, acceptable salt thereof.
2 . The method of claim 1 , wherein the apilimod is apilimod dimesylate.
3 . The method of claim 1 , wherein the colorectal cancer is refractory or metastatic.
4 . The method of claim 1 , wherein the composition is an oral dosage form or a dosage form suitable for intravenous administration.
5 . The method of claim 1 , wherein the colorectal cancer is a stage III or stage IV colorectal cancer, as defined by the TNM staging system of the World Health Organization.
6 . The method of claim 1 , further comprising administering at least one additional active agent.
7 . The method of claim 1 , wherein the at least one additional active agent is a therapeutic agent or a non-therapeutic agent, or a combination thereof.
8 . The method of claim 7 , wherein the therapeutic agent is selected from the group consisting of a protein kinase inhibitor, a PD-1/PDL-1 pathway inhibitor, a platinum based anti-neoplastic agent, a topoisomerase inhibitor, a nucleoside metabolic inhibitor, an alkylating agent, an intercalating agent, a tubulin binding agent, a BRAT inhibitor, and combinations thereof.
9 . The method of claim 8 , wherein the therapeutic agent is selected from the group consisting of vemurafenib, oxaliplatin, regorafenib, irinotecan, 5-fluorouracil, pembrolizumab, avelumab, atezolizumab (MPDL3280A), nivolumab (BMS-936558), pidilizumab (MK-3475), MSB0010718C, MEDI4736, and combinations thereof.
10 . The method of claim 9 , wherein the therapeutic agent s vemurafenib.
11 . The method of claim 9 , wherein the therapeutic agent s regorafenib.
12 . The method of claim 9 , wherein the cancer is refractory or metastatic colorectal cancer.
13 . The method of claim 1 further comprising administering a non-therapeutic agent selected to ameliorate one or more side effects of the apilimod.
14 . (canceled)
15 . The method of claim 7 , wherein the non-therapeutic agent is selected from the group consisting of ondansetron, granisetron, dolasetron and palonosetron.
16 . The method of claim 7 , wherein the non-therapeutic agent is selected from the group consisting of pindolol and risperidone.
17 . (canceled)
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24 . (canceled)
25 . A method for inducing or potentiating autophagy or apoptosis in a colorectal cancer cell, the method comprising contacting the cell with a composition comprising apilimod dimesylate.
26 . A method for identifying a human colorectal cancer patient for treatment with a combination therapy comprising apilimod and vemurafenib, the method comprising assaying a biological sample of the subject's cancer for one or more of the V600E BRAF protein mutation, the V600K BRAF protein mutation, or the genetic equivalents thereof, wherein a subject having either of these mutations is identified as a patient for treatment with a combination therapy comprising apilimod and vemurafenib.
27 . (canceled)
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29 . A method for identifying a colorectal cancer as sensitive to apilimod treatment, the method comprising assaying the expression of the SNX10 gene in a sample of the cancer, such as a biopsy sample, wherein high SNX10 gene expression indicates that the colorectal cancer is sensitive to apilimod treatment.