Combination therapy for cancer treatment

Patent metadata

Field	Value
Publication number	US-10478428-B2
Application number	US-201715852551-A
Country	US
Kind code	B2
Filing date	Dec 22, 2017
Priority date	Aug 20, 2015
Publication date	Nov 19, 2019
Grant date	Nov 19, 2019

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 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 ovarian cancer.

2. The method according to claim 1 , wherein each administration of liposomal irinotecan is administered as a dose of 70 mg/m 2 (free base).

3. The method of claim 2 , wherein the patient does not have a BRCA1 or a BRCA2 mutation and wherein the PARP inhibitor is selected from the group consisting of niraparib, olaparib, veliparib, rucaparib and talazoparib.

4. The method according to claim 2 , wherein the PARP inhibitor is administered on each of consecutive days 5 to 10.

5. The method of claim 4 , wherein the patient does not have a BRCA1 or a BRCA2 mutation and 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 is composed of 1,2-distearoyl-sn-glycero-3-phosphochline, 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 ovarian 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 7 , wherein the effective irinotecan plasma clearing interval is 2, 3, 4 or 5 days.

9. The method of claim 8 , wherein the patient does not have a BRCA1 or a BRCA2 mutation.

10. The method of claim 9 , wherein the effective amount of MM-398 liposomal irinotecan is 70 mg/m 2 (free base) administered during a 90 minute infusion.

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

12. A method of treating a patient diagnosed with ovarian 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.

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

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

15. The method of claim 14 , 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.

16. The method of claim 15 , wherein the patient does not have a BRCA1 or a BRCA2 mutation.

17. The method of claim 16 , 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

• A61P35/00

  Antineoplastic agents · 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

• A61K47/20

  containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids · CPC title

• A61K31/55

  having seven-membered rings, e.g. azelastine, pentylenetetrazole · CPC title

• A61K31/502

  ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine · CPC title