Therapy for drug-resistant cancer by administration of anti-HER2 antibody/drug conjugate
AssigneeDaiichi Sankyo Company, Limited
InventorsTakahiro Jikoh, Yusuke Ogitani, Kazutaka Yoshihara, Seiko Endo, Yoshihiko Fujisaki
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Abstract
As treatment effective for HER2-expressing cancer having resistance or refractoriness to an existing anti-HER2 drug, there are provided a therapeutic agent and a treatment method using an antibody-drug conjugate in which a linker and a drug represented by the formula: -(Succinimid-3-yl-N)—CH2CH2CH2CH2CH2—C(═O)-GGFG (SEQ ID NO: 5) —NH—CH2—O—CH2—C(═O)—(NH-DX) are conjugated to an anti-HER2 antibody.
Claims32
A method for treating HER2-expressing cancer having resistance to an existing anti-HER2 drug, comprising administering a dose per administration of a range of 5.4 mg/kg to 6.4 mg/kg of an antibody-drug conjugate in which a linker and a drug represented by the following formula are conjugated to an anti-HER2 antibody to a human patient in need of the treatment of the HER2-expressing cancer having resistance to an existing anti-HER2 drug:
- -(Succinimid-3-yl-N)—CH2CH2CH2CH2CH2—C(═O)-GGFG (SEQ ID NO:
- 5)-NH—CH2—O—CH2—C(═O)—(NH-DX)
- wherein
- (Succinimid-3-yl-N)- has a structure represented by the following formula:
- which is connected to the anti-HER2 antibody at position 3 thereof via a thioether bond and is connected to the methylene group in the linker structure containing this structure on the nitrogen atom at position 1,
- (NH-DX) represents a group represented by the following formula:
- wherein the nitrogen atom of the amino group at position 1 is the connecting position, and
- -GGFG- represents the tetrapeptide residue of -Gly-Gly-Phe-Gly- (SEQ ID NO:
- 5);
- wherein the anti-HER2 antibody comprises (i) a heavy chain consisting of an amino acid sequence consisting of amino acid residues 1 to 449 of SEQ ID NO:
- 1 and a light chain consisting of an amino acid sequence consisting of amino acid residues 1 to 214 of SEQ ID NO:
- 2;
- or (ii) a heavy chain consisting of the amino acid sequence represented by SEQ ID NO:
- 1 and a light chain consisting of the amino acid sequence represented by SEQ ID NO:
- 2.
A method for treating HER2-expressing cancer having resistance to an existing anti-HER2 drug, comprising administering a dose per administration of a range of 5.4 mg/kg to 6.4 mg/kg of an antibody-drug conjugate represented by the following Formula
- to a human patient in need of the treatment of the HER2-expressing cancer having resistance to an existing anti-HER2 drug;
- wherein in the Formula, a drug-linker is conjugated to the anti-HER2 antibody via a thioether bond, and
- n represents an average number of units of the drug-linker structure conjugated per antibody molecule of the antibody-drug conjugate;
- wherein the average number of units of the drug-linker structure conjugated per antibody molecule of the antibody-drug conjugate is 7 to 8;
- wherein the anti-HER2 antibody comprises (i) a heavy chain consisting of an amino acid sequence consisting of amino acid residues 1 to 449 of SEQ ID NO:
- 1 and a light chain consisting of an amino acid sequence consisting of amino acid residues 1 to 214 of SEQ ID NO:
- 2;
- or (ii) a heavy chain consisting of the amino acid sequence represented by SEQ ID NO:
- 1 and a light chain consisting of the amino acid sequence represented by SEQ ID NO:
- 2;
- wherein the antibody-drug conjugate is administered once every 3 weeks;
- and
- wherein the cancer is at least one selected from the group consisting of breast cancer, gastric cancer, colorectal cancer, esophageal cancer, salivary gland cancer, pancreatic cancer, ovarian cancer, uterine cancer, lung cancer, and sarcoma.
Dependencies are inferred from the claim text.