Methods for treating pancreatic cancer using combination therapies comprising liposomal irinotecan

• US 10,980,795 B2
• Filed: 06/19/2018
• Issued: 04/20/2021
• Est. Priority Date: 06/13/2012
• Status: Active Grant

• Current Assignee: IPSEN Biopharm Limited (Ipsen Sa)
• Original Assignee: IPSEN Biopharm Limited (Ipsen Sa)
• Inventors: Bayever, Eliel, Dhindsa, Navreet, Fitzgerald, Jonathan Basil, Laivins, Peter, Moyo, Victor, Niyikiza, Clet, Kim, Jaeyeon
• Primary Examiner(s): Klinkel, Kortney L.
• Assistant Examiner(s): Strong, Tori
• Application Number:
  US16/012,351
• Publication Number:
  US 20190117643A1
• Time in Patent Office: 1,036 Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 31/513 having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• CPC Class Codes: A61K 31/517 ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0019 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 Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

Provided are methods for treating pancreatic cancer in a patient by administering liposomal irinotecan (MM-398) alone or in combination with additional therapeutic agents. In one embodiment, the liposomal irinotecan (MM-398) is co-administered with 5-fluorouracil and leucovorin.

Claims

1. A method of treating metastatic adenocarcinoma of the pancreas in a human patient who has previously been treated with gemcitabine, comprising intravenously administering an antineoplastic therapy to the patient once every two weeks, the therapy consisting of

i) irinotecan sucrose octasulfate salt liposome injection in a dose providing the equivalent of 70 mg/m² of irinotecan free base,

ii) 200 mg/m² of the (l) form of leucovorin or 400 mg/m² of the (l+d) racemic form of leucovorin, and

iii) 2400 mg/m² of 5-fluorouracil.

2. The method of claim 1, wherein the metastatic adenocarcinoma of the pancreas has progressed after treatment with gemcitabine.

3. The method of claim 1, wherein the irinotecan sucrose octasulfate salt liposome injection comprises irinotecan sucrose octasulfate salt, phosphatidylcholine, cholesterol, and a polyethyleneglycol-derivatized phosphatidyl-ethanolamine.

4. The method of claim 3, wherein the polyethylene glycol in the polyethyleneglycol-derivatized phosphatidyl-ethanolamine is N-(methoxy-poly(ethyleneglycol) (M.W. 2000)-oxycarbonyl)-distearoylphosphatidylethanolamine.

5. The method of claim 4, wherein the polyethyleneglycol-derivatized phosphatidyl-ethanolamine is in the amount of approximately one polyethyleneglycol derivatized phosphatidyl-ethanolamine molecule for 200 phosphatidylcholine molecules.

6. The method of claim 4, wherein the irinotecan sucrose octasulfate salt liposome injection comprises phosphatidylcholine, cholesterol, and N-(methoxy-poly(ethyleneglycol) (M.W. 2000)-oxycarbonyl)-distearoylphosphatidylethanolamine in a molar ratio of 3:

2;

0.015.

7. The method of claim 6, further comprising premedicating the human patient with an anti-emetic prior to administering the antineoplastic therapy.

8. The method of claim 6, wherein the irinotecan sucrose octasulfate salt liposome injection is administered followed by the leucovorin, followed by the 5-fluorouracil.

9. The method of claim 8, further comprising premedicating the human patient with an anti-emetic prior to administering the antineoplastic therapy.

10. The method of claim 8, wherein the irinotecan sucrose octasulfate salt liposome injection, leucovorin, and 5-fluorouracil are administered sequentially to the patient beginning on day 1 of a 2-week cycle.

11. The method of claim 10, further comprising premedicating the human patient with an anti-emetic prior to administering the antineoplastic therapy.

12. The method of claim 8, wherein the irinotecan sucrose octasulfate salt liposome injection is administered intravenously over 90 minutes, followed by intravenous administration of leucovorin over 30 minutes, followed by intravenous administration of 5-fluorouracil over 46 hours.

13. The method of claim 12, further comprising premedicating the human patient with an anti-emetic prior to administering the antineoplastic therapy.

14. The method of claim 1, wherein the leucovorin is provided by administering 400 mg/m² of the (l+d) form of leucovorin.

15. The method of claim 14, further comprising premedicating the human patient with an anti-emetic prior to administering the antineoplastic therapy.