Extending time to disease progression or survival in cancer patients

• US 8,691,232 B2
• Filed: 01/21/2011
• Issued: 04/08/2014
• Est. Priority Date: 02/23/2005
• Status: Active Grant

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Derynck, Mika K., Kelsey, Stephen M.
• Primary Examiner(s): Goddard, Laura B
• Application Number:
  US13/010,985
• Publication Number:
  US 20110165157A1
• Time in Patent Office: 1,173 Days
• Field of Search: None
• US Class Current: 424/155.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 31/7068 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/3069 Reproductive system, e.g. ovaria, uterus, testes, prostate
• CPC Class Codes: C07K 16/32 against translation products of oncogenes
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL

Abstract

The present application describes extending time to disease progression or survival in a cancer patient, where the patient'"'"'s cancer displays HER activation, by treating the patient with a HER dimerization inhibitor, such as pertuzumab.

Claims

1. A method for extending time to disease progression (TTP) or survival in cancer patients with metastatic breast cancer which displays HER activation comprising:

(a) administering a HER2 antibody which comprises the variable light and variable heavy amino acid sequences in SEQ ID Nos. 3 and 4 as fixed doses of 420 mg to the patients and (b) measuring TTP or survival in the patients to confirm it is extended.

2. The method of claim 1 wherein the HER2 antibody inhibits HER heterodimerization.

3. The method of claim 1 wherein the cancer displays HER2 activation.

4. The method of claim 3 wherein the cancer displays HER2 overexpression or amplification.

5. The method of claim 1 wherein the HER2 antibody is pertuzumab.

6. The method of claim 1 wherein the HER2 antibody is a naked antibody.

7. The method of claim 1 wherein the HER2 antibody is an intact antibody.

8. The method of claim 1 wherein the HER2 antibody is an antibody fragment comprising an antigen binding region.

9. The method of claim 1 wherein the HER2 antibody is administered as a single anti-tumor agent.

10. The method of claim 1 comprising administering a second therapeutic agent to the patients.

11. The method claim 10 wherein the second therapeutic agent is selected from the group consisting of chemotherapeutic agent, HER antibody, antibody directed against a tumor associated antigen, anti-hormonal compound, cardioprotectant, cytokine, EGFR-targeted drug, anti-angiogenic agent, tyrosine kinase inhibitor, COX inhibitor, non-steroidal anti-inflammatory drug, farnesyl transferase inhibitor, antibody that binds oncofetal protein CA 125, HER2 vaccine, HER targeting therapy, Raf or ras inhibitor, liposomal doxorubicin, topotecan, taxane, dual tyrosine kinase inhibitor, TLK286, EMD-7200, a medicament that treats nausea, a medicament that prevents or treats skin rash or standard acne therapy, a medicament that treats or prevents diarrhea, a body temperature-reducing medicament, and a hematopoietic growth factor.

12. The method of claim 10 wherein the second therapeutic agent comprises trastuzumab.

13. The method of claim 1 wherein TTP is extended.

14. The method of claim 1 wherein survival is extended.

15. The method of claim 1 wherein administration of the HER2 antibody extends TTP or survival at least about 20% more than TTP or survival achieved by administering an approved anti-tumor agent to the cancer patients.

16. A method for extending time to disease progression (TTP) or survival in breast cancer patients comprising:

(a) administering a HER2 antibody to the patients as fixed doses of about 420 mg of the HER2 antibody so as to extend TTP or survival in the patients, wherein the HER2 antibody comprises the variable light and variable heavy amino acid sequences in SEQ ID Nos. 3 and 4, respectively, and (b) measuring TTP or survival in the patients to confirm it is extended.

17. The method of claim 16 which extends TTP.

18. The method of claim 16 which extends survival.

19. The method of claim 16 wherein the patients are metastatic breast cancer patients.

20. The method of claim 19 wherein the cancer displays HER2 activation.

21. The method of claim 20 wherein the cancer displays amplified or overexpressed HER2.

22. The method of claim 16 wherein the fixed doses of about 420 mg of the HER2 antibody are administered about every three weeks.

23. The method of claim 22 wherein a loading dose of 840 mg of the HER2 antibody is administered followed by the fixed doses of about 420 mg of the HER2 antibody.

24. The method of claim 16 comprising administering a second therapeutic agent to the patients.

25. The method of claim 24 wherein the second therapeutic agent comprises trastuzumab.

26. The method of claim 16 wherein the HER2 antibody is pertuzumab.

27. A method for extending time to disease progression (TTP) or survival in breast cancer patients comprising:

(a) administering pertuzumab to the patients as a loading dose of 840 mg followed by fixed doses of about 420 mg of the pertuzumab every three weeks and (b) measuring TTP or survival to confirm it is extended in the patients.

28. The method of claim 27 which extends TTP.

29. The method of claim 27 which extends survival.

30. The method of claim 27 wherein the patients have metastatic breast cancer.

31. The method of claim 27 wherein the cancer displays HER2 activation.

32. The method of claim 31 wherein the cancer displays amplified or overexpressed HER2.

33. The method of claim 27 comprising administering a second therapeutic agent to the patients.

34. The method of claim 33 wherein the second therapeutic agent comprises trastuzumab.