Granted Patent B2

US 12,364,691 · App. 17/824,421 · Granted Jul 22, 2025

Inventors: Eliel Bayever (New York, NY); Navreet Dhindsa (Boston, MA); Jonathan Basil Fitzgerald (Arlington, MA); Peter Laivins (Rowayton, CT); Victor Moyo (Ringoes, NJ); Clet Niyikiza (Gulf Mills, PA); Jaeyeon Kim (Lexington, MA)

Assignee: Ipsen Biopharm Ltd.

A61K31/4745A61K9/0019A61K9/127A61K9/1271A61K31/513A61K31/519A61K47/24A61K47/26A61K47/28

Abstract

Claims (19)

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/m 2 of irinotecan hydrochloride trihydrate,

(b) 200 mg/m 2 of the (1) form of leucovorin or 400 mg/m 2 (1+d) leucovorin infused over 30 minutes,

(c) the 5-FU is administered at a total dose of 2,400 mg/m 2 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/m 2 of irinotecan hydrochloride trihydrate;

(b) 200 mg/m 2 of the (1) form of leucovorin or 400 mg/m 2 (1+d) leucovorin infused over 30 minutes,

(c) the 5-FU is administered at a total dose of 2,400 mg/m 2 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.

Assignments (2)

Continuity (7)

References Cited (400)