Dosage and administration for preventing cardiotoxicity in treatment with ERbB2-targeted immunoliposomes comprising anthracycline chemotherapeutic agents

Patent metadata

Field	Value
Publication number	US-9610249-B2
Application number	US-201514832103-A
Country	US
Kind code	B2
Filing date	Aug 21, 2015
Priority date	Dec 6, 2010
Publication date	Apr 4, 2017
Grant date	Apr 4, 2017

Abstract

Methods for determining dosage of HER2-targeted anthracycline-containing immunoliposomes are disclosed, as are methods of treating cancer patients with HER2-positive tumors using dosages so determined. Upon administration, the dosages share the low cardiotoxicity profile of standard dosages of non-immunoliposomal (untargeted), anthracycline-containing liposomes.

First claim

What is claimed is:

1. A method of treating a human patient with locally advanced/unresectable or metastatic advanced breast cancer that overexpresses ErbB2 (HER2) receptors, the method comprising administering to the human patient 30 mg/m 2 of doxorubicin (doxorubicin HCl equivalent) in a MM302 doxorubicin HER-2 targeted immunoliposome once every three weeks to treat the breast cancer that overexpresses HER2.

2. The method of claim 1 , wherein the breast cancer characterized by overexpression of HER2 receptor is further characterized as being HER2 FISH positive.

3. The method of claim 1 , wherein the breast cancer characterized by overexpression of ErbB2 receptor further characterized as expressing an average of at least 200,000 cell surface ErbB2 receptors per cell.

4. The method of claim 1 , wherein the cumulative concentration of doxorubicin administered to the patient in the MM302 doxorubicin HER-2 targeted immunoliposome is less than 550 mg/m 2 .

5. The method of claim 1 , wherein the patient is anthracycline-naïve prior to treatment with the MM302 doxorubicin HER-2 targeted immunoliposome.

6. The method of claim 1 , wherein the MM302 doxorubicin HER-2 targeted immunoliposome is administered intravenously over 60 minutes.

7. The method of claim 1 , comprising treating the patient for breast cancer that is characterized by expression of HER2 receptor characterized as being HER2 3+ or HER2 2+ and HER2 FISH positive.

8. The method of claim 7 , wherein the patient is anthracycline-naive prior to treatment with the MM302 doxorubicin HER-2 targeted immunoliposome.

9. The method of claim 1 , wherein the breast cancer is HER2 3+ .

10. The method of claim 1 , wherein the breast cancer is FISH positive.

11. The method of claim 1 , wherein the breast cancer is HER2 2+ and is FISH positive.

12. The method of claim 1 , wherein the breast cancer is HER2 3+ and is FISH positive.

13. The method of claim 1 , wherein the cumulative concentration of doxorubicin administered to the patient in the MM-302 doxorubicin HER2 targeted immunoliposome is less than 550 mg/m 2 .

14. The method of claim 1 , wherein the breast cancer is HER2 3+ and the patient is anthracycline naïve.

15. The method of claim 1 , wherein the breast cancer is HER2 2+ and HER2 FISH positive and the patient is anthracycline naïve.

16. The method of claim 14 , wherein the cumulative concentration of doxorubicin administered to the patient in the MM302 doxorubicin HER2 targeted immunoliposome is less than 550 mg/m 2 .

17. A method of treating a human patient with locally advanced/unresectable or metastatic advanced breast cancer that is HER2 FISH positive and HER2 2+ or is HER2 3+ , the method comprising administering to the human patient 30 mg/m 2 of doxorubicin (HCl equivalent) in a MM302 doxorubicin HER-2 targeted immunoliposome once every three weeks to treat the breast cancer, wherein the human patient is anthracycline-naïve prior to treatment with the MM302 doxorubicin HER-2 targeted immunoliposome.

18. The method of claim 17 , wherein the breast cancer is HER2 2+ and FISH positive.

19. The method of claim 17 , wherein the breast cancer is HER2 3+ .

20. A method of treating a human patient with breast cancer that is HER2 FISH positive and HER2 2+ or is HER2 3+ , the method comprising administering to the human patient 30 mg/m 2 of doxorubicin (doxorubicin HCl equivalent) in a MM302 doxorubicin HER-2 targeted immunoliposome once every three weeks to treat the breast cancer.

21. The method of claim 20 , wherein the breast cancer is FISH positive.

22. The method of claim 20 , wherein the human patient is anthracycline-naïve prior to treatment with the MM302 doxorubicin HER-2 targeted immunoliposome and the cumulative concentration of doxorubicin administered to the human patient is less than 550 mg/m 2 .

Assignees

• Merrimack Pharmaceuticals Inc
• Merrimack Pharmaceuticals Inc

Inventors

• Reynolds Joseph G
• Olivier Jr Kenneth J
• Hendriks Bart S
• Wickham Thomas
• Klinz Stephan
• Geretti Elena

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P15/00

  Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives · CPC title

• A61K47/6851

  the antibody targeting a determinant of a tumour cell · CPC title

• A61K31/7042 Primary

  Compounds having saccharide radicals and heterocyclic rings · CPC title