Formulations of milciclib and therapeutic combinations of the same for use in the treatment of cancer

Abstract

This application relates to methods of treating and/or preventing cancer (e.g., non-small cell lung cancer, renal cell carcinoma, hepatocellular carcinoma, thyroid carcinoma, colorectal cancer, gastrointestinal stromal tumors, breast cancer, prostate cancer, pancreatic cancer, or thymoma) in patients in need thereof comprising administering to the patient a therapeutically effective amount of a CDK inhibitor (e.g., milciclib) in combination with a therapeutically effective amount of another anticancer drug (e.g., sorafenib, lenvatinib, regorafenib, sunitinib, nivolumab, gemcitabine, and palbociclib).

1 . A method of treating or preventing cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a CDK inhibitor, or a pharmaceutically acceptable salt, isomer, or tautomer thereof, in combination with a therapeutically effective amount of another anticancer drug. 
     
     
         2 . The method of  claim 1 , wherein the cancer is non-small cell lung cancer, renal cell carcinoma, hepatocellular carcinoma, thyroid carcinoma, melanoma, multiple myeloma, mantle cell lymphoma, non-Hodgkin's lymphoma, colorectal cancer, acute lymphocytic leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, skin cancer, ovarian cancer, gastrointestinal stromal tumors, breast cancer, prostate cancer, pancreatic cancer, or thymoma. 
     
     
         3 . The method of  claim 1 , wherein the CDK inhibitor is milciclib or a pharmaceutically acceptable salt thereof, and the other anticancer drug is sorafenib, lenvatinib, regorafenib, sunitinib, nivolumab, gemcitabine, palbociclib, afatinib, alectinib, axitinib, bortezomib, bosutinib, cabozantinib, carfilzomib, ceritinib, cobimetinib, crizotinib, dabrafenib, erlotinib, gefitinib, ibrutinib, idelalisib, imatinib, ixazomib, lapatinib, nilotinib, nintedanib, niraparib, osimertinib, pazopanib, pegaptanib, ponatinib, rucaparib, ruxolitinib, sonidegib, tofacitinib, trametinib, vandetanib, vemurafenib, vismodegibor, or a pharmaceutically acceptable salt thereof. 
     
     
         4 . The method of  claim 3 , wherein the other anticancer drug is sorafenib or a pharmaceutically acceptable salt thereof. 
     
     
         5 . The method of  claim 4 , wherein the therapeutically effective amount of sorafenib is 400 mg twice daily, 200 mg twice daily, or 200 mg once daily. 
     
     
         6 . The method of  claim 4 , wherein the cancer is renal cell carcinoma or thyroid carcinoma. 
     
     
         7 . The method of  claim 3 , wherein the other anticancer drug is lenvatinib or a pharmaceutically acceptable salt thereof. 
     
     
         8 . The method of  claim 7 , wherein the therapeutically effective amount of lenvatinib is 8, 10, 12, 14, 18, 20, 22, 24, 26, 28, 30, 32, or 34 mg once daily. 
     
     
         9 . The method of  claim 7 , wherein the cancer is renal cell carcinoma or thyroid carcinoma. 
     
     
         10 . The method of  claim 3 , wherein the other anticancer drug is regorafenib or a pharmaceutically acceptable salt thereof. 
     
     
         11 . The method of  claim 10 , wherein the therapeutically effective amount of regorafenib is 80, 100, or 120 mg once daily for three weeks, followed by one week of no administration, wherein the cycle is optionally repeated. 
     
     
         12 . The method of  claim 10 , wherein the cancer is colorectal cancer or gastrointestinal stromal tumors. 
     
     
         13 . The method of  claim 3 , wherein the other anticancer drug is sunitinib or a pharmaceutically acceptable salt thereof. 
     
     
         14 . The method of  claim 13 , wherein the therapeutically effective amount of sunitinib is 12.5, 25, 37.5, 50, 62.5, 75, 87.5, or 100 mg once daily continuously or for 4 weeks followed by two weeks of no administration, wherein the cycle is optionally repeated. 
     
     
         15 . The method of  claim 13 , wherein the cancer is renal cell carcinoma or gastrointestinal stromal tumors. 
     
     
         16 . The method of  claim 3 , wherein the other anticancer drug is nivolumab. 
     
     
         17 . (canceled) 
     
     
         18 . The method of  claim 3 , wherein the other anticancer drug is gemcitabine or a pharmaceutically acceptable salt thereof. 
     
     
         19 . The method of  claim 18 , wherein the therapeutically effective amount of gemcitabine is 1000 mg/m 2  over 30 minutes once weekly for seven weeks, followed by one week of no administration, wherein the cycle is optionally repeated. 
     
     
         20 . (canceled) 
     
     
         21 . The method of  claim 3 , wherein the other anticancer drug is palbociclib or a pharmaceutically acceptable salt thereof. 
     
     
         22 . The method of  claim 21 , wherein the therapeutically effective amount of palbociclib is 75, 100, or 125 mg once daily for 3 weeks followed by one week of no administration, wherein the cycle is optionally repeated. 
     
     
         23 . (canceled) 
     
     
         24 . The method of  claim 3 , wherein the therapeutically effective amount of milciclib is 50, 75, 100, 125, or 150 mg once daily for four consecutive days, followed by non-administration for 3 consecutive days, wherein the cycle is optionally repeated. 
     
     
         25 .- 52 . (canceled) 
     
     
         53 . The method of  claim 1 , wherein the CDK inhibitor and the other anticancer drug are administered in temporal proximity. 
     
     
         54 .- 62 . (canceled)