JP-2022531894-A5 -

Dates

Publication Date

20230518

Application Date

20200511

Description

In a preferred embodiment, the priming dose of the combined first and second antibodies is 0.1 mg/kg. Following the priming dose, further treatment doses may be administered to subjects in need of treatment based on a bi-weekly administration schedule (day 1 of a 14-day cycle (Q2W)). The treatment dose following the priming dose may range from 0.3 mg/kg to 9 mg/kg for each antibody. In one embodiment of the present invention, the treatment dose administered on day 1 of a 14-day cycle is in the range of 0.15 mg/kg to 9 mg/kg for each of the first and second antibodies. In one embodiment of the present invention, the treatment dose administered on day 1 of a 14-day cycle is in the range of 0.15 mg/kg to 9 mg/kg for each of the first and second antibodies. In a preferred embodiment, the treatment dose administered on day 1 of a 14-day cycle is in the range of 0.15 mg/kg to 3 mg/kg for each of the first and second antibodies. In one aspect of the present invention, the combined treatment dose of the first and second antibodies administered on day 1 of a 14-day cycle is in the range of 0.3 mg/kg to 6 mg/kg. [Invention 1001] A method for treating a solid tumor or hematological malignancy in a subject, comprising administering to the subject in need a first antibody bound to DR5 and a second antibody bound to DR5, or pharmaceutically acceptable salts thereof, wherein the first antibody and the second antibody i) For the first four cycles, on the 1st and 8th day of the 14-day cycle; or ii) On the 1st and 8th days of the first 14-day cycle; or iii) On the first day of the first 14-day cycle; or iv) On the first day of the first and second 14-day cycles The method, wherein the administration is performed, and then the administration is performed on day 1 of a 14-day cycle. [Invention 1002] The method of the present invention 1001, wherein the first antibody comprises a variable heavy chain region and a variable light chain region, wherein the variable heavy chain region comprises CDR1, CDR2, and CDR3 sequences having SEQ ID NO: 1, 8, and 3, respectively; and the variable light chain region comprises CDR1, CDR2, and CDR3 sequences having SEQ ID NO: 5, FAS, and SEQ ID NO: 6, respectively. [Invention 1003] The method of the present invention 1001, wherein the second antibody comprises a variable heavy chain region and a variable light chain region, wherein the variable heavy chain region comprises CDR1, CDR2, and CDR3 sequences having SEQ ID NO: 10, 2, and 11, respectively; and the variable light chain region comprises CDR1, CDR2, and CDR3 sequences having SEQ ID NO: 13, RTS, and SEQ ID NO: 14, respectively. [Invention 1004] The first antibody and the second antibody each comprise the Fc region of human IgG1, wherein the Fc region comprises the E430G mutation at the amino acid position corresponding to E430 in human IgG1, and the amino acid position is determined by Eu numbering, according to any one of the methods 1001 to 1003 of the present invention. [Invention 1005] The method according to any one of the present invention 1001 to 1004, wherein the first antibody comprises a heavy chain and a light chain, respectively, as shown in SEQ ID NO: 30 and 27. [Invention 1006] The method according to any one of the present invention 1001 to 1004, wherein the first antibody comprises a heavy chain and a light chain indicated by SEQ ID NO: 47 and 27, respectively. [Invention 1007] The method according to any one of the present invention 1001 to 1006, wherein the second antibody comprises a heavy chain and a light chain, respectively, as shown in SEQ ID NO: 48 and 35. [Invention 1008] The method according to any one of the present invention 1001 to 1006, wherein the second antibody comprises a heavy chain and a light chain, respectively, as shown in SEQ ID NO: 32 and 35. [Invention 1009] The method according to any one of items 1001 to 1008 of the present invention, wherein the solid tumor is selected from the group consisting of colorectal cancer (CRC), non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), renal cell carcinoma (RCC), gastric cancer, pancreatic cancer, and urothelial carcinoma. [Invention 1010] The method according to any one of items 1001 to 1008 of the present invention, wherein the hematological malignancy is selected from the group consisting of leukemia, myeloid leukemia, acute myeloid leukemia, myelodysplastic syndrome, lymphoma, non-Hodgkin lymphoma, Hodgkin lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, multiple myeloma, chronic lymphocytic leukemia, or myelodysplastic syndrome. [Invention 1011] Any method of the present invention, wherein the first antibody and the second antibody or pharmaceutically acceptable salts thereof are administered simultaneously, separately, or sequentially. [Invention 1012] Any method of the present invention, wherein the first antibody and the second antibody or pharmaceutically acceptable salts thereof are administered simultaneously. [