JPWO2020106898A5 - - Google Patents

Claims (50)

in the manufacture of a medicament for treating cancer,
a) riboceranib or a pharmaceutically acceptable salt thereof;
b) paclitaxel or a pharmaceutically acceptable salt thereof;
Use of combinations containing 2. Use according to claim 1, wherein said combination comprises riboceranib free base. 2. Use according to claim 1, wherein said combination comprises a pharmaceutically acceptable salt of riboceranib. 4. Use according to claim 3, wherein the pharmaceutically acceptable salt of riboceranib is the mesylate. Use according to any one of claims 1 to 4, wherein the riboceranib is in an amount of 100 mg to 1000 mg based on the weight of free base. Use according to any one of claims 1 to 5, wherein the riboceranib is in an amount of less than 700 mg based on the weight of free base. Use according to any one of claims 1 to 6, wherein the riboceranib is in an amount of about 400 mg based on the weight of free base. Use according to any one of claims 1 to 7, wherein the total daily dose of riboceranib is less than 685 mg by weight of free base. Use according to any one of claims 1 to 8, wherein said riboceranib is formulated for oral administration. The use of any one of claims 1-9, wherein the riboceranib is formulated as a dry powder, liquid, capsule, pellet, or tablet. Use according to any one of claims 1 to 10, wherein said riboceranib is formulated as a tablet. 12. Use according to claim 11, wherein the tablet is a film-coated tablet. 13. Use according to claim 11 or claim 12, wherein said tablet comprises said riboceranib in an amount of about 100 mg. 13. Use according to claim 11 or claim 12, wherein said tablet comprises said riboceranib in an amount of about 200 mg. wherein the tablet further comprises one or more of pregelatinized starch, microcrystalline cellulose, sodium starch glycolate, povidone (K-2 9/32), colloidal silicon dioxide, magnesium stearate, and Opadry white. Use according to any one of paragraphs 11-14. Use according to any one of claims 1 to 15, wherein said riboceranib is administered once daily. Use according to any one of claims 1 to 16, comprising paclitaxel free base. Use according to any one of claims 1 to 16, comprising a pharmaceutically acceptable salt of paclitaxel. Use according to claim 17 or claim 18, wherein said paclitaxel is in an amount of 10 mg/m ² to 100 mg/m ² . Use according to any one of claims 17-19, wherein said paclitaxel is in an amount of about 80 mg/m ² . Use according to any one of claims 17-20, wherein the paclitaxel is formulated for oral or parenteral administration. Use according to any one of claims 17-21, wherein the paclitaxel is formulated for parenteral administration. 23. Use according to claim 22, wherein said paclitaxel administration is selected from intravenous administration, intradermal administration, intramuscular administration, or subcutaneous administration. Use according to any one of claims 17-23, wherein the paclitaxel is formulated for intravenous administration. The use of any one of claims 17-24, wherein said paclitaxel is administered after administration of said riboceranib. The use of any one of claims 17-25, wherein the paclitaxel is administered over a period of about 30 minutes to about 1 hour. Use according to any one of claims 17-26, wherein the paclitaxel is administered no more than once a week. 27. Use according to any one of claims 17-26, wherein the paclitaxel is administered once a week, once a month, twice a month, or three times a month. Use according to any one of the preceding claims, wherein the paclitaxel is formulated as a composition comprising nanoparticles comprising paclitaxel and a protein carrier. Use according to any one of the preceding claims, wherein the paclitaxel is formulated as a composition comprising nanoparticles comprising paclitaxel and albumin. 31. Use according to claim 29 or claim 30, wherein said paclitaxel in said nanoparticulate state is coated with albumin. Use according to any one of claims 29 to 31, wherein the nanoparticles have an average diameter of about 200 nm or less. Use according to any one of claims 30-32, wherein the weight ratio of albumin to paclitaxel in the nanoparticles is about 9:1. Use according to any one of claims 1 to 33, wherein a premedication is administered prior to the administration of paclitaxel. 35. Use according to claim 34, wherein the premedication comprises one or more of dexamethasone, diphenhydramine and/or famotidine. the premedication is
20 mg of dexamethasone;
50 mg of diphenhydramine;
35. Use according to claim 34, comprising famotidine 20 mg. Use according to any one of claims 34 to 36, wherein said premedication is formulated for intravenous administration. The cancer is acanthoma, acinoma, acoustic neuroma, lentigo melanoma acral, hidradenoma acral, acute eosinophilic leukemia, acute lymphoblastic leukemia, acute megakaryoblastic leukemia, acute mono Leukemia, acute myeloblastic leukemia with maturation, acute myeloid dendritic cell leukemia, acute myeloid leukemia, acute promyelocytic leukemia, adamantinoma, adenocarcinoma, adenoid cystic carcinoma, adenoma, adenoid tooth primary tumor, adrenocorticocytoma, adult T-cell leukemia, aggressive NK-cell leukemia, AIDS-related cancer, AIDS-related lymphoma, alveolar soft tissue sarcoma, enamel epithelial fibroma, anal cancer, anaplastic large cell lymphoma, anaplastic thyroid cancer, immunoblastic T-cell lymphoma, angiomyolipoma, angiosarcoma, appendiceal cancer, astrocytoma, atypical teratoid rhabdoid tumor, basal cell carcinoma, basal-like cell tumor, B-cell leukemia, B-cell lymphoma, Bellini ductal carcinoma, biliary tract cancer, bladder cancer, blastoma, bone cancer, bone tumor, brain stem glioma, brain tumor, breast cancer, Brenner tumor, bronchial tumor, bronchioloalveolar carcinoma, pheochromoma, Burkitt's lymphoma, carcinoma of unknown primary, carcinoid tumor, carcinoma, carcinoma in situ, penile carcinoma, carcinoma of unknown primary, carcinosarcoma, Castorman's disease, central nervous system embryonal tumor, cerebellar astrocytoma, cerebral astrocytoma, cervical astrocytoma Cancer, intrahepatic cholangiocarcinoma, chondroma, chondrosarcoma, chordoma, choriocarcinoma, choroid plexus papilloma, chronic lymphocytic leukemia, chronic monocytic leukemia, chronic myelogenous leukemia, chronic myeloproliferative disease, chronic neutrophil leukemia, clear cell tumor, colon cancer, colorectal cancer, craniopharyngioma, cutaneous T-cell lymphoma, Degos disease, dermatofibrosarcoma protuberance, dermoid cyst, desmoplastic small round cell tumor, diffuse large B cell tumor Lymphoma, dysembryonic neuroepithelial tumor, embryonal cancer, endoderm sinus tumor, endometrial cancer, endometrial uterine cancer, endometrial tumor, enteropathy-associated T-cell lymphoma, ependymoblastoma, Ependymoma, epithelioid sarcoma, erythroleukemia, esophageal cancer, sensory neuroblastoma, Ewing tumor family, Ewing sarcoma family, Ewing sarcoma, extracranial germ cell tumor, extragonadal germ cell tumor, extrahepatic cholangiocarcinoma, extramammary page Jett's disease, fallopian duct carcinoma, fetal inclusion malformation, fibroma, fibrosarcoma, follicular lymphoma, follicular thyroid cancer, gallbladder cancer, neuronal glioma, gangneuromas, gastric cancer, gastric lymphoma, gastrointestinal cancer, gastrointestinal tract Carcinoid tumor, gastrointestinal stromal tumor, germ cell tumor, germinomas, gestational choriocarcinoma, gestational trophoblastic tumor, giant cell tumor of bone, glioblastoma multiforme, glioma, gliomatosis, glomus tumor , glucagonoma, gonadoblastoma, granulosacytoma, hairy cell leukemia, head and neck cancer, heart cancer, hemangioblastoma , hemangiopericytoma, angiosarcoma, hematological malignancy, hepatocellular carcinoma, hepatosplenic T-cell lymphoma, hereditary breast and ovarian cancer syndrome, Hodgkin lymphoma, hypopharyngeal carcinoma, hypothalamic glioma, inflammatory breast cancer, intraocular melanoma cancer, islet cell carcinoma, islet cell tumor, juvenile myelomonocytic leukemia, Kaposi's sarcoma, renal cancer, Kratskin tumor, Krukenberg tumor, laryngeal cancer, lentigo malignant melanoma, leukemia, lip cancer, oral cancer, fat sarcoma, lung cancer, luteinoma, lymphangioma, lymphangiosarcoma, lymphoepithelioma, lymphocytic leukemia, lymphoma, macroglobulinemia, malignant fibrous histiocytoma, malignant fibrous histiocytoma of bone, malignant glioma, Malignant mesothelioma, malignant peripheral schwannoma, malignant rhabdoid tumor, malignant triton tumor, MALT lymphoma, mantle cell lymphoma, mast cell leukemia, mediastinal germ cell tumor, mediastinal tumor, bone marrow thyroid cancer, medulloblastoma, medullary Epithelioma, melanoma, meningioma, Merkel cell tumor, mesothelioma, metastatic squamous cell carcinoma of the neck of unknown primary, metastatic urothelial carcinoma, mixed Müllerian tumor, monocytic leukemia, mouth cancer, mucin malignant tumor, multiple endocrine neoplasia, multiple myeloma, mycosis fungoides, myelodysplastic disease, myelodysplastic syndrome, myelogenous leukemia, myelogenous sarcoma, spinal proliferative disease, myxoma, nasal cavity carcinoma, nasopharynx Carcinoma, nasopharyngeal carcinoma, neoplasm, schwannoma, neuroblastoma, neurofibroma, neuroma, nodular melanoma, non-Hodgkin lymphoma, non-melanoma skin cancer, non-small cell lung cancer, ocular tumor, ocular tumor Dendroastrocytoma, oligodendroglioma, oncocytoma, optic nerve sheath meningioma, oral cancer, oropharyngeal cancer, osteosarcoma, ovarian cancer, epithelial ovarian cancer, ovarian germ cell tumor, ovarian low malignant potential tumor, Paget's disease of the breast, Pancoast tumor, pancreatic cancer, papillary thyroid cancer, papillomatosis, paraganglioma, paranasal sinus cancer, parathyroid cancer, penile cancer, perivascular epithelioid cell tumor, pharyngeal cancer, pheochromocytoma , intermediate pineal parenchymal tumor, pineoblastoma, pituitary cell tumor, pituitary adenoma, pituitary tumor, plasma cell neoplasm, pleuropulmonary blastoma, polyembryonoma, precursor T-lymphoblastic lymphoma , primary central nervous system lymphoma, primary exudative lymphoma, primary hepatocellular carcinoma, primary liver cancer, primary peritoneal cancer, primitive neuroectodermal tumor, prostate cancer, peritoneal pseudomyxoma, rectal cancer, renal cell carcinoma, respiratory carcinoma involving the NUT gene on chromosome 15, retinoblastoma, rhabdomyomas, rhabdomyosarcoma, Richter's transformation, sacrococcygeal teratoma, salivary gland cancer, sarcoma, schwannomatosis, Sebaceous gland carcinoma, secondary neoplasm, seminioma, serous tumor, Sertoli-Leydig cell tumor, genital cord stromal tumor, Sézary syndrome, signet ring cell tumor, skin cancer, small blue round cell cystic tumor, small cell carcinoma, small cell lung cancer, small cell lymphoma, small bowel cancer, soft tissue sarcoma, somatostatin-producing tumor, soot warts, spinal cord tumor, spinal tumor, splenic marginal zone lymphoma, squamous cell carcinoma, gastric cancer, table Enlarged melanoma, supratentorial primitive neuroepithelial tumor, surface epithelial stromal tumor, synovial sarcoma, T-cell acute lymphoblastic leukemia, T-cell large granular lymphocytic leukemia, T-cell leukemia, T-cell lymphoma , T-cell prolymphocytic leukemia, teratoma, terminal lymphadenocarcinoma, testicular cancer, cysticoma, laryngeal cancer, thymic carcinoma, thymoma, thyroid cancer, transitional cell carcinoma of the renal pelvis and ureter, transitional cell carcinoma, urine Tubular carcinoma, urethral cancer, genitourinary tumor, uterine sarcoma, uveal melanoma, vaginal cancer, Verner-Morrison syndrome, verrucous carcinoma, optic glioma, vulvar cancer, Waldenström macroglobulinemia, Warthin tumor, 38. Use according to any one of claims 1 to 37, selected from Wilms tumor, or any combination thereof. Use according to any one of the preceding claims, wherein said cancer is a cancer affecting the digestive system. said cancer is anal cancer, intestinal cancer, colon cancer, colorectal cancer, esophageal cancer, gallbladder cancer, biliary tract cancer, gastric cancer, gastrointestinal stromal tumor (gist), gastroesophageal junction cancer, intestinal cancer, liver cancer, neuroendocrine 40. Use according to claim 39, which is a tumor, pancreatic cancer, peritoneal cancer, rectal cancer, small bowel cancer, gastric cancer, or a combination thereof. Use according to any one of claims 1 to 40, wherein said cancer is gastric cancer. Use according to any one of claims 1 to 40, wherein said cancer is gastroesophageal junction cancer. Use according to any one of claims 1 to 40, wherein the cancer is advanced gastric cancer or advanced gastroesophageal junction cancer. Use according to any one of claims 1 to 40, wherein said cancer is recurrent metastatic gastric cancer or recurrent metastatic gastroesophageal junction cancer. Use according to any one of the preceding claims, wherein said cancer is metastatic gastric cancer or metastatic gastroesophageal junction cancer. Anticancer agents, antiproliferative agents, chemotherapeutic agents, immunomodulatory agents, antiangiogenic agents, anti-inflammatory agents, alkylating agents, steroidal anti-inflammatory agents, non-steroidal anti-inflammatory agents, pain relievers, leukotriene antagonists, β2- Consisting of agonists, anticholinergics, hormones, biologics, tubulin-binding agents, glucocorticoids, corticosteroids, antimicrobials, antihistamines, antiemetics, antimalarials, antivirals, and antibiotics 46. Use according to any one of claims 1-45, further comprising one or more additional agents selected from the group and optionally radiotherapy. in the manufacture of a medicament for treating cancer,
a) riboceranib or a pharmaceutically acceptable salt thereof;
b) Use of combinations containing paclitaxel up to 80 mg/m ² . in the manufacture of a medicament for treating cancer,
a) 685 mg or less of riboceranib or a pharmaceutically acceptable salt thereof;
b) Use of combinations containing paclitaxel. in the manufacture of a medicament for treating cancer,
a) 685 mg or less of riboceranib or a pharmaceutically acceptable salt thereof;
b) Use of combinations containing paclitaxel up to 80 mg/m ² . in the manufacture of a medicament for treating cancer,
a) riboceranib or a pharmaceutically acceptable salt thereof;
b) the use of a combination containing paclitaxel,
The use, wherein said riboceranib and said paclitaxel act synergistically.