JPWO2021173832A5 - - Google Patents

Claims (59)

An immunoconjugate of the formula Ab-[TA] _r or a pharmaceutically acceptable salt thereof, where "Ab" represents human epidermal growth factor receptor type 2 ( is an antibody construct having an antigen-binding domain that binds to HER2), where "TA" has the formula:

(wherein n is about 2 to about 25) and r is an average therapeutic agent-to-antibody ratio of about 1 to about 10, where about 0 01 to about 100 mg/kg of the immunoconjugate or a pharmaceutically acceptable salt thereof is administered to a subject having cancer. An immunoconjugate of the formula Ab-[TA] _r or a pharmaceutically acceptable salt thereof, where "Ab" represents human epidermal growth factor receptor type 2 ( is an antibody construct having an antigen-binding domain that binds to HER2), where "TA" has the formula:

(wherein n is about 2 to about 25) and r is an average therapeutic agent-to-antibody ratio of 1 to 10, wherein the immunoconjugate or a pharmaceutically acceptable salt thereof is administered to a subject having cancer about every 3 days to about every 45 days. 3. The use of claim 2, wherein from about 0.01 to about 100 mg/kg of the immunoconjugate is administered to the subject during each administration. Use according to any one of claims 1 to 3, wherein the immunoconjugate is administered in the form of a composition comprising the immunoconjugate and a pharmaceutically acceptable carrier thereof. Use according to any one of claims 1 to 4, wherein the immunoconjugate is administered intravenously to the subject. 6. The use of claim 5, wherein the immunoconjugate is administered intravenously to the subject over a period of about 1 to about 240 minutes. 7. The use of any one of claims 1-6, further comprising administering to the subject having cancer an effective amount of additional therapy. Additional therapy may include surgery, radiation therapy, high-intensity focused ultrasound therapy (HIFU), chemotherapy, cryosurgery, hormonal therapy, immunotherapy, targeted monoclonal antibodies, antibody-drug conjugates, tyrosine kinase inhibitors, or combinations thereof. The use of claim 7 selected from the group consisting of. 8. Use according to claim 7, wherein the additional therapy is immunotherapy. Use according to any one of claims 7 to 9, wherein the additional therapy is an immune checkpoint inhibitor. Use according to any one of claims 7 to 10, wherein the additional therapy is an IgG1 or IgG4 antibody. 12. The use of claim 11, wherein the IgG1 or IgG4 antibody is an anti-programmed cell death protein 1 (PD-1) or anti-programmed death ligand 1 (PD-L1) antibody. The use according to claim 12, wherein the antibody is an anti-PD-1 antibody. The anti-PD-1 antibody has a variable light (VL) chain region comprising CDR1 having the amino acid sequence of SEQ ID NO: 1, CDR2 having the amino acid sequence of SEQ ID NO: 2, and CDR3 having the amino acid sequence of SEQ ID NO: 3; and SEQ ID NO: 14. The use of claim 13, comprising a variable heavy (VH) chain region comprising CDR1 having the amino acid sequence of SEQ ID NO: 4, CDR2 having the amino acid sequence of SEQ ID NO: 5, and CDR3 having the amino acid sequence of SEQ ID NO: 6. The anti-PD-1 antibody has a variable light (VL) chain region comprising CDR1 having the amino acid sequence of SEQ ID NO: 58, CDR2 having the amino acid sequence of SEQ ID NO: 59, and CDR3 having the amino acid sequence of SEQ ID NO: 60; and SEQ ID NO: 14. The use of claim 13, comprising a variable heavy (VH) chain region comprising CDR1 having an amino acid sequence of SEQ ID NO: 61, CDR2 having an amino acid sequence of SEQ ID NO: 62, and CDR3 having an amino acid sequence of SEQ ID NO: 63. The anti-PD-1 antibody has a variable light (VL) chain region comprising CDR1 having the amino acid sequence of SEQ ID NO: 64, CDR2 having the amino acid sequence of SEQ ID NO: 65, and CDR3 having the amino acid sequence of SEQ ID NO: 66; and SEQ ID NO: 14. The use of claim 13, comprising a variable heavy (VH) chain region comprising CDR1 having an amino acid sequence of SEQ ID NO: 67, CDR2 having an amino acid sequence of SEQ ID NO: 68, and CDR3 having an amino acid sequence of SEQ ID NO: 69. The anti-PD-1 antibody has a variable light (VL) chain region comprising CDR1 having the amino acid sequence of SEQ ID NO: 70, CDR2 having the amino acid sequence of SEQ ID NO: 71, and CDR3 having the amino acid sequence of SEQ ID NO: 72; and SEQ ID NO: 14. The use of claim 13, comprising a variable heavy (VH) chain region comprising CDR1 having an amino acid sequence of SEQ ID NO: 73, CDR2 having an amino acid sequence of SEQ ID NO: 74, and CDR3 having an amino acid sequence of SEQ ID NO: 75. The anti-PD-1 antibody has a variable light (VL) chain region comprising CDR1 having the amino acid sequence of SEQ ID NO: 76, CDR2 having the amino acid sequence of SEQ ID NO: 77, and CDR3 having the amino acid sequence of SEQ ID NO: 78; and SEQ ID NO: 14. The use of claim 13, comprising a variable heavy (VH) chain region comprising CDR1 having an amino acid sequence of SEQ ID NO: 79, CDR2 having an amino acid sequence of SEQ ID NO: 80, and CDR3 having an amino acid sequence of SEQ ID NO: 81. 13. The use of claim 12, wherein the antibody is an anti-PD-L1 antibody. The anti-PD-L1 antibody has a variable light (VL) chain region comprising CDR1 having the amino acid sequence of SEQ ID NO: 7, CDR2 having the amino acid sequence of SEQ ID NO: 8, and CDR3 having the amino acid sequence of SEQ ID NO: 9; and SEQ ID NO: 20. The use of claim 19, comprising a variable heavy (VH) chain region comprising CDR1 having an amino acid sequence of SEQ ID NO: 10, CDR2 having an amino acid sequence of SEQ ID NO: 11, and CDR3 having an amino acid sequence of SEQ ID NO: 12. The anti-PD-L1 antibody has a variable light (VL) chain region comprising CDR1 having the amino acid sequence of SEQ ID NO: 13, CDR2 having the amino acid sequence of SEQ ID NO: 14, and CDR3 having the amino acid sequence of SEQ ID NO: 15; and SEQ ID NO: 20. The use of claim 19, comprising a variable heavy (VH) chain region comprising CDR1 having an amino acid sequence of 16, CDR2 having an amino acid sequence of SEQ ID NO: 17, and CDR3 having an amino acid sequence of SEQ ID NO: 18. 22. The use of any one of claims 12-21, wherein about 100 mg to about 2,000 mg of antibody is administered to the subject. Use according to any one of claims 12 to 21, wherein the antibody is administered intravenously to the subject. 24. The use of claim 23, wherein the antibody is administered intravenously to the subject over a period of about 1 minute to about 60 minutes. Use according to any one of claims 12 to 24, wherein the immunoconjugate is administered simultaneously with the antibody. 26. The use of any one of claims 12-25, wherein the antibody is administered about every 7 days to about every 35 days. Use according to any one of claims 1 to 26, wherein the cancer is a HER2-expressing cancer or a HER2-amplified cancer. Use according to any one of claims 1 to 27, wherein the cancer is breast cancer. 29. The use of claim 28, wherein the cancer is HER2 overexpressing breast cancer. Use according to any one of claims 1 to 27, wherein the cancer is gastric cancer. 31. The use of claim 30, wherein the cancer is HER2 overexpressing gastric cancer. Use according to any one of claims 1 to 27, wherein the cancer is gastroesophageal junction adenocarcinoma. Use according to any one of claims 1 to 27, wherein the cancer is colorectal cancer. Use according to any one of claims 1 to 27, wherein the cancer is endometrial cancer. Use according to any one of claims 1 to 27, wherein the cancer is salivary gland cancer. Use according to any one of claims 1 to 27, wherein the cancer is lung cancer. Use according to any one of claims 1 to 36, wherein the cancer has metastasized. Use according to any one of claims 1 to 37, wherein the cancer is HER2 IHC1+/ISH+. Use according to any one of claims 1 to 37, wherein the cancer is HER2 IHC1+/ISH-. Use according to any one of claims 1 to 37, wherein the cancer is HER2 IHC2+/ISH+. Use according to any one of claims 1 to 37, wherein the cancer is HER2 IHC2+/ISH-. Use according to any one of claims 1 to 37, wherein the cancer is HER2 IHC3+. Use according to any one of claims 1 to 42, wherein the cancer expresses or overexpresses HER2 as determined by gene expression. Use according to any one of claims 1 to 42, wherein the cancer exhibits HER2 amplification. 45. The use of claim 44, wherein the cancer is ISH+. 45. The use of claim 44, wherein the cancer is ISH-. Use according to any one of claims 44 to 46 , wherein HER2 amplification is determined by sequencing. 48. The use of any one of claims 44-47, wherein HER2 amplification is determined by next generation sequencing (NGS). Use according to any one of claims 1 to 48, wherein r is about 1 to about 6. 50. The use of claim 49, wherein r is about 2 to about 4. Use according to any one of claims 1 to 50, wherein n is about 6 to about 12. 52. The use of claim 51, wherein n is about 10. 53. The use of any one of claims 1 to 52, wherein "Ab" is trastuzumab, a biosimilar thereof, or a biobetter thereof. 53. The use of any one of claims 1 to 52, wherein "Ab" is pertuzumab, a biosimilar thereof, or a biobetter thereof. 53. The use of any one of claims 1 to 52, wherein "Ab" is trastuzumab. 53. The use of any one of claims 1 to 52, wherein the "Ab" is a biosimilar of trastuzumab. 53. The use of any one of claims 1-52, wherein the "Ab" is a biosimilar of pertuzumab. 58. The use of any one of claims 1-57, wherein the subject is treated for about 1 month to about 48 months. Use according to any one of claims 1 to 58, wherein the subject is a human.