Methods for treating pancreatic cancer using combination therapies comprising liposomal irinotecan

Patent metadata

Field	Value
Publication number	US-10980795-B2
Application number	US-201816012351-A
Country	US
Kind code	B2
Filing date	Jun 19, 2018
Priority date	Jun 13, 2012
Publication date	Apr 20, 2021
Grant date	Apr 20, 2021

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.

First claim

What is claimed is:

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/m 2 of irinotecan free base,
ii) 200 mg/m 2 of the (l) form of leucovorin or 400 mg/m 2 of the (l+d) racemic form of leucovorin, and
iii) 2400 mg/m 2 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/m 2 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.

Assignees

• Ipsen Biopharm Ltd

Inventors

• Bayever Eliel
• Dhindsa Navreet
• Fitzgerald Jonathan Basil
• Laivins Peter
• Moyo Victor
• Niyikiza Clet
• Kim Jaeyeon

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

• A61P35/00

  Antineoplastic agents · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P1/18

  for pancreatic disorders, e.g. pancreatic enzymes · CPC title

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title