Claims for Patent: 12,364,691

Summary for Patent: 12,364,691

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:	US17/824,421
Patent Claims:	1. A method of treating metastatic adenocarcinoma of the pancreas in human patients after disease progression following gemcitabine-based therapy, the method comprising intravenously administering to the patients with metastatic adenocarcinoma of the pancreas who have a Karnofsky Performance status of equal to or greater than 70, albumin of greater or equal to 3 g/dl, and serum bilirubin within the normal range: (1) liposomal irinotecan, (2) leucovorin, and (3) 5-fluorouracil (5-FU), in an administration cycle that repeats every two weeks wherein: (a) the liposomal irinotecan is administered by infusion over 90 minutes to the patients on day 1 of each cycle as intravenous irinotecan sucrose octasulfate salt liposome injection in an amount of irinotecan moiety that provides the equivalent of 80 mg/m2 of irinotecan hydrochloride trihydrate, (b) 200 mg/m2 of the (1) form of leucovorin or 400 mg/m2 (1+d) leucovorin infused over 30 minutes, (c) the 5-FU is administered at a total dose of 2,400 mg/m2 infused over 46 h, and (d) no antineoplastic agent is administered for treatment of the pancreatic cancer other than the liposomal irinotecan dose recited in (a) and the 5-FU dose recited in (c); wherein the liposomal irinotecan is a unilamellar lipid bilayer vesicle of approximately 80-140 nm in diameter encapsulating an aqueous space that contains irinotecan complexed in a gelated or precipitated state as a salt with sucrose octasulfate, with the lipid membrane of the liposome being composed of 3 molar parts distearoylphosphatidylcholine (DSPC), 2 molar parts cholesterol, and 0.015 molar parts N-methoxy-terminated polyethylene glycol (MW 2000)-distearoylphosphatidyl ethanolamine (PEG2000-DSPE); and further wherein the liposomal irinotecan has an irinotecan entity to lipid weight ratio of 0.5:1. 2. The method of claim 1, wherein the human patients are not homozygous for UGT1A1*28. 3. The method of claim 2, wherein the liposomal irinotecan administration is followed by intravenous administration of the leucovorin, followed by intravenous administration of the 5-FU, and each infusion is initiated on the first day of the cycle. 4. A method of treating metastatic adenocarcinoma of the pancreas in human patients after disease progression following gemcitabine-based therapy, the method comprising intravenously administering to the patients with metastatic adenocarcinoma of the pancreas who have a Karnofsky Performance status of equal to or greater than 70, albumin of greater or equal to 3 g/dl, and serum bilirubin within the normal range: (1) liposomal irinotecan, (2) leucovorin, and (3) 5-fluorouracil (5-FU), in an administration cycle that can be repeated every 2 weeks, wherein: (a) the liposomal irinotecan is administered by infusion over 90 minutes to patients homozygous for the UGT1A1 *28 allele on day 1 of cycle 1 as intravenous irinotecan sucrose octasulfate salt liposome injection in an amount of irinotecan moiety that provides the equivalent of 60 mg/m2 of irinotecan hydrochloride trihydrate; (b) 200 mg/m2 of the (1) form of leucovorin or 400 mg/m2 (1+d) leucovorin infused over 30 minutes, (c) the 5-FU is administered at a total dose of 2,400 mg/m2 infused over 46 h; and (d) no antineoplastic agent is administered for treatment of the pancreatic cancer other than the liposomal irinotecan dose recited in (a) and the 5-FU dose recited in (c); wherein the liposomal irinotecan is a unilamellar lipid bilayer vesicle of approximately 80-140 nm in diameter encapsulating an aqueous space that contains irinotecan complexed in a gelated or precipitated state as a salt with sucrose octasulfate, with the lipid membrane of the liposome being composed of 3 molar parts distearoylphosphatidylcholine (DSPC), 2 molar parts cholesterol, and 0.015 molar parts N-methoxy-terminated polyethylene glycol (MW 2000)-distearoylphosphatidyl ethanolamine (PEG2000-DSPE); and further wherein the liposomal irinotecan has an irinotecan entity to lipid weight ratio of 0.5:1. 5. The method of claim 4, wherein the liposomal irinotecan administration is followed by intravenous administration of the leucovorin, followed by intravenous administration of the 5-FU, and each infusion is initiated on the first day of the cycle.