Claims for Patent: 11,369,597

Summary for Patent: 11,369,597

Title:	Methods for treating pancreatic cancer using combination therapies
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.
Inventor(s):	Eliel Bayever, Navreet Dhindsa, Jonathan Basil FITZGERALD, Peter Laivins, Victor Moyo, Clet Niyikiza, Jaeyeon Kim
Assignee:	Ipsen Biopharm Ltd
Application Number:	US16/012,372
Patent Claims:	1. A method of treating metastatic adenocarcinoma of the pancreas in a human patient who has previously been treated with the antineoplastic agent gemcitabine, comprising intravenously administering to the patient once every two weeks, an antineoplastic therapy consisting of: a) irinotecan sucrose octasulfate salt liposome injection in an amount providing the equivalent of 70 mg/m2 of irinotecan free base, the irinotecan sucrose octasulfate salt liposome injection comprising irinotecan sucrose octasulfate encapsulated in liposomes, wherein, following administration in patients, the irinotecan sucrose octasulfate salt liposome injection has a mean total SN-38 terminal elimination half-life in the plasma of 67.8±44.5 hours; b) 200 mg/m2 of the (l) form of leucovorin or 400 mg/m2 of the (l+d) racemic form of leucovorin; and c) 2,400 mg/m2 of the antineoplastic agent 5-fluorouracil. 2. The method of claim 1, wherein the irinotecan sucrose octasulfate salt liposome injection is administered intravenously over 90 minutes, followed by intravenous administration of the leucovorin over 30 minutes, followed by intravenous administration of the 5-fluorouracil over 46 hours. 3. The method of claim 2, wherein the patient has metastatic adenocarcinoma of the pancreas that has progressed on gemcitabine-based therapy prior to the administration of the irinotecan sucrose octasulfate salt liposome injection. 4. The method of claim 3, wherein, following administration in patients, the irinotecan sucrose octasulfate salt liposome injection has an area under the plasma concentration curve extrapolated to time infinity (AUC0-∞) of the mean total SN-38 that increases less than proportionally with the dose of irinotecan sucrose octasulfate salt liposome injection. 5. The method of claim 3, wherein, following administration in patients, the irinotecan sucrose octasulfate salt liposome injection has a mean total SN-38 area under the plasma concentration curve extrapolated to time infinity (AUC0-∞) of 620±329 h·ng/mL. 6. The method of claim 3, wherein, following administration in patients, the irinotecan sucrose octasulfate salt liposome injection has a mean total SN-38 maximum plasma concentration of 5.4±3.4 nanograms/mL. 7. The method of claim 3, wherein the leucovorin is provided by administering 400 mg/m2 of the (l+d) form of leucovorin. 8. The method of claim 2, further comprising premediating the human patient with an anti-emetic prior to administering the antineoplastic therapy. 9. The method of claim 1, wherein the irinotecan sucrose octasulfate salt liposome injection contains N-(methoxy-poly(ethyleneglycol) (M.W. 2000)-oxycarbonyl)-distearoylphosphatidylethanolamine. 10. The method of claim 1, wherein the 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. 11. The method of claim 1, wherein the liposomes have an average size of from about 80 to about 140 nm as determined by volume-averaged mean of the liposome size distribution by quasi-elastic light scattering (QELS) using Gaussian model. 12. The method of claim 11, wherein the liposomes have an average size of about 110 nm as determined by volume-averaged mean of the liposome size distribution by quasi-elastic light scattering (QELS) using Gaussian model. 13. The method of claim 1, wherein the liposomes have been filtered through a 0.2 micron filter.