Nanoliposomal irinotecan for use in treating small cell lung cancer

Patent metadata

Field	Value
Publication number	US-11318131-B2
Application number	US-201716302050-A
Country	US
Kind code	B2
Filing date	May 17, 2017
Priority date	May 18, 2015
Publication date	May 3, 2022
Grant date	May 3, 2022

Abstract

Novel therapies for the treatment of small cell lung cancer (SCLC) include the administration of an antineoplastic therapy consisting of liposomal irinotecan administered once every two weeks, optionally including the administration of other non-antineoplastic agents to the patient such as the administration of a corticosteroid and an anti-emetic to the patient prior to the administration of the irinotecan liposome.

First claim

We claim:

1. A method of treating a human patient diagnosed with small cell lung cancer (SCLC) following disease progression on or after first-line platinum-based therapy for the SCLC, wherein the prior first-line platinum-based therapy has been discontinued, the method comprising administering to the human patient an antineoplastic therapy once every two weeks, the antineoplastic therapy consisting of liposomal irinotecan in a dose providing the equivalent of 70 mg/m 2 irinotecan free base.

2. The method of claim 1 , wherein the platinum-based therapy comprises the prior, discontinued administration of cisplatin or carboplatin to treat the human patient diagnosed with SCLC.

3. The method of claim 1 , wherein the human patient has a blood ANC greater than 1,500 cells/microliter without the use of hematopoietic growth factors, prior to the administration of the liposomal irinotecan.

4. The method of claim 1 , wherein the human patient has a blood platelet count of greater than 100,000 cells per microliter, prior to the administration of the liposomal irinotecan.

5. The method of claim 1 , wherein the human patient has a blood hemoglobin greater than 9 g/dL, prior to the administration of the liposomal irinotecan.

6. The method of claim 1 , wherein the human patient has a serum creatinine of less than or equal to 1.5×ULN and a creatinine clearance of greater than or equal to 40 mL/min prior to the administration of the liposomal irinotecan.

7. The method of claim 1 , wherein the human patient has not received a topoisomerase I inhibitor prior to administration of the liposomal irinotecan.

8. The method of claim 1 , wherein the human patient has not received more than a single platinum-based therapy prior to administration of the liposomal irinotecan.

9. The method of claim 1 , wherein the administration of the antineoplastic therapy comprises the steps of:
(a) preparing a pharmaceutically acceptable injectable composition by diluting the liposomal irinotecan into 500 mL 5% Dextrose Injection (D5W) or 0.9% Sodium Chloride Injection to obtain the injectable composition; and
(b) administering the injectable composition from step (a) to the patient in an infusion.

10. The method of claim 1 , further comprising administering to the human patient a corticosteroid and an antiemetic prior to each administration of the antineoplastic therapy.

11. The method of claim 1 , comprising administering to the human patient the antineoplastic therapy once every two weeks in a six-week cycle.

12. The method of claim 11 , wherein the platinum-based therapy comprises the prior, discontinued administration of cisplatin or carboplatin to treat the human patient diagnosed with SCLC.

13. The method of claim 12 , wherein the human patient has one or more of the following prior to the administration of the liposomal irinotecan:
(a) a blood ANC greater than 1,500 cells/microliter without the use of hematopoietic growth factors;
(b) a blood platelet count of greater than 100,000 cells per microliter;
(c) a blood hemoglobin greater than 9 g/dL; and
(d) a serum creatinine of less than or equal to 1.5×ULN and a creatinine clearance of greater than or equal to 40 mL/min.

14. The method of claim 13 , wherein the human patient has not received a topoisomerase I inhibitor prior to administration of the liposomal irinotecan; and the human patient has not received more than a single platinum-based therapy prior to administration of the liposomal irinotecan.

15. The method of claim 13 , wherein the method comprises administering the antineoplastic therapy for at least three six-week cycles.

16. The method of claim 11 , wherein the administration of the antineoplastic therapy comprises the steps of:
(a) preparing a pharmaceutically acceptable injectable composition by diluting the liposomal irinotecan into 500 mL 5% Dextrose Injection (D5W) or 0.9% Sodium Chloride Injection to obtain the injectable composition; and
(b) administering the injectable composition from step (a) to the patient in an infusion.

17. The method of claim 16 , further comprising administering to the human patient a corticosteroid and an antiemetic prior to each administration of the antineoplastic therapy.

18. The method of claim 1 , comprising administering to the human patient the antineoplastic therapy once every two weeks for a total of at least three six-week cycles, wherein the human patient has the following prior to the administration of each antineoplastic therapy of liposomal irinotecan:
(a) a blood ANC greater than 1,500 cells/microliter without the use of hematopoietic growth factors;
(b) a blood platelet count of greater than 100,000 cells per microliter;
(c) a blood hemoglobin greater than 9 g/dL; and
(d) a serum creatinine of less than or equal to 1.5×ULN and a creatinine clearance of greater than or equal to 40 mL/min.

19. The method of claim 18 , wherein:
(e) the human patient has not received a topoisomerase I inhibitor prior to administration of the liposomal irinotecan and has not received more than a single platinum-based therapy prior to administration of the liposomal irinotecan; and
(f) the method further comprises administering to the human patient a corticosteroid and an antiemetic prior to each administration of the antineoplastic therapy.

20. The method of claim 19 , wherein the administration of the antineoplastic therapy comprises the steps of:
(i) preparing a pharmaceutically acceptable injectable composition by diluting the liposomal irinotecan into 500 mL 5% Dextrose Injection (D5W) or 0.9% Sodium Chloride Injection to obtain the injectable composition; and
(ii) administering the injectable composition from step (i) to the patient in an infusion.

21. The method of claim 9 , comprising administering the injectable composition from step (a) to the patient in a 90-minute infusion.

22. The method of claim 16 , comprising administering the injectable composition from step (a) to the patient in a 90-minute infusion.

23. The method of claim 20 , comprising administering the injectable composition from step (i) to the patient in a 90-minute infusion.

24. The method of claim 1 , wherein the liposomal irinotecan comprises unilamellar lipid bilayer vesicles, encapsulating an aqueous space containing irinotecan in a gelated or precipitated state as the sucrose octasulfate salt.

25. The method of claim 24 , wherein the vesicles comprise phosphatidylcholine, cholesterol, and a polyethyleneglycol-derivatized phosphatidyl-ethanolamine.

26. The method of claim 25 , wherein the polyethylene glycol in the polyethyleneglycol-derivatized phosphatidyl-ethanolamine is methoxy terminated and has a molecular weight of 2000, and the phosphatidyl-ethanolamine is distearoylphosphatidyl ethanolamine.

27. The method of claim 25 , wherein the polyethyleneglycol-derivatized phosphatidyl-ethanolamine is in the amount of approximately one polyethyleneglycol-derivatized phosphatidyl-ethanolamine molecule for 200 phospholipid molecules in the irinotecan liposome.

28. The method of claim 26 , wherein the sucrose octasulfate salt liposome injection comprises phosphatidylcholine, cholesterol, and methoxy-terminated polyethylene glycol-distearoylphosphatidyl ethanolamine in a molar ratio of 3:2:0.015.

29. The method of claim 24 , wherein the vesicles comprise 1,2-distearoyl-sn-glycero-3-phosphoch

Assignees

• Ipsen Biopharm Ltd

Inventors

• Adiwijaya Bambang
• Fitzgerald Jonathan Basil
• Lee Helen

Classifications

• A61K31/4745 Primary

  condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48) · CPC title

• A61K9/127 Primary

  Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/573

  substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone · CPC title