Use of anti-HER2 antibody-drug conjugate in cancer treatment

Patent metadata

Field	Value
Publication number	US-12150944-B2
Application number	US-201916979251-A
Country	US
Kind code	B2
Filing date	Apr 30, 2019
Priority date	May 11, 2018
Publication date	Nov 26, 2024
Grant date	Nov 26, 2024

Abstract

Disclosed in the present invention is the use of an anti-HER2 antibody-drug conjugate in cancer treatment. Further provided in the present invention is the use of a pharmaceutically acceptable salt, stereoisomer, or metabolite thereof, or a solvate of each of the foregoing in the manufacture of a medicament for the prophylaxis and/or treatment of a cancer insensitive or irresponsive to a treatment with a HER2-targeting agent.

First claim

What is claimed is:

1. A method of treating a cancer insensitive or irresponsive to a treatment with a HER2-targeting agent, comprising administering a therapeutically effective amount of a conjugate of Formula (I), a pharmaceutically acceptable salt or stereoisomer thereof, or a solvate of the foregoing to a subject in need thereof,

wherein
A is a moiety obtained after the removal of n amino groups from an anti-HER2 antibody or an active fragment thereof, and n is an integer of 1, 2, 3, 4, 5, 6, 7, or 8.

2. The method according to claim 1 , wherein the conjugate of Formula (I) has the structure represented by Formula (I-1),

wherein A 1 is a moiety obtained after the removal of 2 amino groups from Trastuzumab.

3. The method according to claim 1 , wherein the cancer is a breast or gastric cancer, and the breast or gastric cancer comprises a HER2-positive breast or gastric cancer insensitive or irresponsive to a treatment with a HER2-targeting agent.

4. The method according to claim 3 , wherein the HER2-positive breast or gastric cancer comprises a HER2-positive breast or gastric cancer with drug resistance to a HER2-targeting agent.

5. The method according to claim 1 , wherein the cancer comprises a breast or gastric cancer with low HER2 expression.

6. The method according to claim 5 , wherein the breast or gastric cancer with low HER2 expression is a breast or gastric cancer with a HER2 expression level of IHC 1+, IHC 1+ to 2+ in a clinical test, or an IHC 2+/FISH negative breast or gastric cancer.

7. The method according to claim 1 , wherein the HER2-targeting agent is selected from the group consisting of an anti-HER2 monoclonal antibody, an anti-HER2 antibody drug conjugate (ADC), an anti-HER2 bispecific antibody and a chemical drug targeting HER2.

8. The method according to claim 1 , wherein the treatment with a HER2-targeting agent comprises a treatment with Trastuzumab and/or T-DM1.

9. The method according to claim 1 , wherein the method comprises administering to a patient a therapeutically effective amount of the conjugate of Formula (I), the pharmaceutically acceptable salt or stereoisomer thereof or the solvate of the foregoing at a dose of 0.1-15 mg/kg body weight.

10. The method according to claim 9 , wherein the method further comprises the step of evaluating whether the patient's cancer is insensitive or irresponsive to a treatment with a HER2-targeting agent prior to the administration, wherein the patient's cancer is a breast or gastric cancer, and the evaluation comprises evaluating whether the patient's breast or gastric cancer has drug resistance to a HER2-targeting agent, or evaluating whether the patient's breast or gastric cancer is a cancer with low HER2 expression.

11. The method according to claim 1 , wherein the method comprises the following steps:
(1) treating a patient having HER2-positive cancer with a HER2-targeting agent and monitoring whether the patient has drug resistance to the HER2-targeting agent, wherein the patient's cancer is a breast or gastric cancer; and
(2) administering a therapeutically effective amount of the conjugate of Formula (I), the pharmaceutically acceptable salt or stereoisomer thereof, or the solvate of the foregoing to the patient having HER2-positive breast or gastric cancer with drug resistance to the HER2-targeting agent.

12. The method according to claim 1 , wherein the method comprises the following steps:
(1) treating a patient having HER2-positive cancer with a HER2-targeting agent and monitoring the disease progression of the cancer, wherein the HER2-positive cancer is a breast or gastric cancer; and
(2) administering a therapeutically effective amount of the conjugate of Formula (I), the pharmaceutically acceptable salt or stereoisomer thereof, or the solvate of the foregoing to the patient upon disease progression.

13. The method according to claim 1 , wherein the method comprises the following steps:
(1) testing the HER2 expression level in a cancer patient, wherein the cancer is a breast or gastric cancer; and
(2) when the HER2 expression is low, administering a therapeutically effective amount of the conjugate of Formula (I), the pharmaceutically acceptable salt or stereoisomer thereof, or the solvate of the foregoing to the patient.

14. The method according to claim 2 , wherein the cancer comprises a HER2-positive breast or gastric cancer insensitive or irresponsive to a treatment with a HER2-targeting agent.

15. The method according to claim 2 , wherein the cancer comprises a breast or gastric cancer with low HER2 expression.

16. The method according to claim 2 , wherein the HER2-targeting agent is Trastuzumab, Pertuzumab, ABP 980, GB221, MYL-1401O, CT-P6, EG12014, HD201, ONS-1050, PF-05280014, HD201, Trastuzumab-dttb or HLX02, or an antibody-drug conjugate comprising Trastuzumab, Pertuzumab, ABP 980, GB221, MYL-1401O, CT-P6, EG12014, HD201, ONS-1050, PF-05280014, HD201, Trastuzumab-dttb or HLX02.

17. The method according to claim 2 , wherein the method comprises administering to a cancer patient a therapeutically effective amount of the conjugate of Formula (I-1), the pharmaceutically acceptable salt or stereoisomer thereof or the solvate of the foregoing at a dose of 0.1-15 mg/kg body weight, wherein the cancer is a breast or gastric cancer.

18. The method according to claim 17 , wherein the method further comprises the step of evaluating whether the patient's breast or gastric cancer is insensitive or irresponsive to a treatment with a HER2-targeting agent prior to the administration.

19. The method according to claim 1 , wherein, A is a moiety obtained after the removal of n amino groups from Trastuzumab or Pertuzumab.

20. The method according to claim 4 , wherein the breast cancer is metastatic breast cancer, locally advanced breast cancer or recurrent breast cancer; and the gastric cancer is advanced gastric cancer or metastatic gastric cancer.

21. The method according to claim 5 , wherein the breast cancer is metastatic breast cancer, locally advanced breast cancer or recurrent breast cancer; and the gastric cancer is advanced gastric cancer or metastatic gastric cancer.

22. The method according to claim 7 , wherein the HER2-targeting agent is Trastuzumab, Pertuzumab, ABP 980, GB221, MYL-1401O, CT-P6, EG12014, HD201, ONS-1050, PF-05280014, HD201, Trastuzumab-dttb or HLX02, or an antibody-drug conjugate comprising Trastuzumab, Pertuzumab, ABP 980, GB221, MYL-1401O, CT-P6, EG12014, HD201, ONS-1050, PF-05280014, HD201, Trastuzumab-dttb or HLX02 as the targeting component.

23. The method according to claim 14 , wherein the HER2-positive breast or gastric cancer comprises a HER2-positive breast or gastric cancer with drug resistance to a HER2-targeting agent.

24. The method according to claim 23 , wherein the breast cancer is metastatic breast cancer, locally advanced breast cancer or recurrent breast cancer; and the gastric cancer is advanced gastric cancer or metastatic gastric cancer.

25. The method according to claim 15 , wherein the breast cancer is metastatic breast cancer, locally advanced breast cancer or recurrent breast cancer; and the gastric cancer is advanced gastric cancer or metastatic gastric cancer.

Assignees

• Sichuan Kelun Biotech Biopharmaceutical Co Ltd

Inventors

• Song Hongmei
• Yuan Xiaoxi
• Wang Jing
• Xiao Liang
• Xue Tongtong
• Liu Ping
• Wang Lichun
• Wang Jingyi

Classifications

• A61P35/04

  specific for metastasis · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/517

  ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine · CPC title

• A61K47/65

  Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers · CPC title

• A61K47/6879

  the immunoglobulin having two or more different antigen-binding sites, e.g. bispecific or multispecific immunoglobulin · CPC title