Combination therapy for cancer treatment

Patent metadata

Field	Value
Publication number	US-11844795-B2
Application number	US-202217703312-A
Country	US
Kind code	B2
Filing date	Mar 24, 2022
Priority date	Aug 20, 2015
Publication date	Dec 19, 2023
Grant date	Dec 19, 2023

Abstract

Combination therapies for treating cancer comprising administration of a topoisomerase-1 inhibitor and a PARP inhibitor are provided. The topoisomerase-1 inhibitor can be delivered as a liposomal formulation that provides for prolonged accumulation of the topoisomerase-1 inhibitor within a tumor relative to outside of the tumor. Therapeutic benefit can thereby be obtained by delaying the administration of the PARP inhibitor after each administration of a liposomal irinotecan formulation until the accumulation of the topoisomerase inhibitor in the tumor is sufficiently greater than outside the tumor to result in increased efficacy of the PARP inhibitor and topoisomerase inhibitor within the tumor, while reducing the peripheral toxicity of the combination therapy. The therapies disclosed herein are useful in the treatment of human cancers with solid tumors, including cervical cancer.

First claim

The invention claimed is:

1. A method of treating a patient having a solid tumor, the method comprising:
i) administering to the patient liposomal irinotecan once every two weeks; and
ii) administering a Poly(ADP-ribose) Polymerase (PARP) inhibitor daily for 3 to 10 days between consecutive administrations of the liposomal irinotecan wherein the PARP inhibitor is administered starting at least 2 days after the liposomal irinotecan and ending at least 1 day prior to the administration of additional liposomal irinotecan, wherein the patient has been diagnosed with small cell lung cancer.

2. The method of claim 1 , wherein each administration of liposomal irinotecan is administered as a dose providing the equivalent of 70 mg/m 2 irinotecan free base.

3. The method of claim 1 , wherein the PARP inhibitor is selected from the group consisting of niraparib, olaparib, veliparib, rucaparib and talazoparib.

4. The method according to claim 1 , wherein the PARP inhibitor is administered on each of consecutive days 5 to 10.

5. The method of claim 4 , wherein the PARP inhibitor is selected from the group consisting of niraparib, olaparib, veliparib, rucaparib and talazoparib.

6. A method of treating a patient with cancer and having a tumor, the method comprising:
i) administering to the patient an effective amount of liposomal irinotecan, wherein the liposomal irinotecan is a unilamellar lipid bilayer vesicle, which encapsulates irinotecan sucrosofate salt and the vesicle comprises 1,2-distearoyl-sn-glycero-3-phosphocholine, cholesterol, and methoxy-terminated polyethylene glycol (MW 2000)-distearoylphosphatidylethanolamine, at a weight ratio of 6.81 mg:2.22 mg:0.12 mg; and
ii) administering to the patient an effective amount of a PARP inhibitor selected from the group consisting of niraparib, olaparib, veliparib, rucaparib and talazoparib, wherein the PARP inhibitor is administered after an effective irinotecan plasma clearing interval, wherein the patient has been diagnosed with small cell lung cancer.

7. The method of claim 6 , wherein the effective irinotecan plasma clearing interval is from about 48 to about 120 hours.

8. The method of claim 6 , wherein the effective irinotecan plasma clearing interval is 2, 3, 4 or 5 days.

9. The method of claim 6 , wherein the effective amount of liposomal irinotecan is a dose providing the equivalent of 70 mg/m 2 irinotecan free base administered during a 90 minute infusion.

10. The method of claim 6 , wherein each administration of the PARP inhibitor is administered at a dose of from about 20 mg/day to about 800 mg/day.

11. A method of treating a patient diagnosed with small cell lung cancer and having a solid tumor, the method comprising administering to the patient an antineoplastic therapy in a 28-day treatment cycle, the antineoplastic therapy consisting of:
i) intravenously administering to the patient an effective amount of a liposomal irinotecan only on days 1 and 15 of the treatment cycle, the liposomal irinotecan having an irinotecan terminal elimination half-life of about 26.8 hours and a maximal irinotecan plasma concentration of about 38.0 micrograms/ml; and
ii) administering an effective amount of a PARP inhibitor to the patient on days 5-12 and 19-25 or 3-12 and 17-25 of the treatment cycle.

12. The method of claim 11 , wherein the PARP inhibitor is selected from the group consisting of niraparib, olaparib, veliparib, rucaparib and talazoparib.

13. The method of claim 11 , wherein the therapeutically effective amount of the liposomal irinotecan is a dose providing the equivalent of 70 mg/m 2 irinotecan free base administered during a 90 minute infusion.

14. The method of claim 11 , further comprising administering one or more subsequent 28-day treatment cycles of the antineoplastic therapy to the patient in the absence of disease progression or unacceptable toxicity during the prior treatment cycle of the antineoplastic therapy.

15. The method of claim 11 , wherein each administration of the PARP inhibitor is administered at a dose of from about 20 mg/day to about 800 mg/day.

Assignees

• Ipsen Biopharm Ltd

Inventors

• Blanchette Sarah F
• Drummond Daryl C
• Fitzgerald Jonathan Basil
• Moyo Victor

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

• A61K9/0019

  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 title

• A61K9/127 Primary

  Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant · CPC title

• A61K9/1271

  Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911}) · CPC title

• A61K31/04

  Nitro compounds · CPC title