Combination therapy for cancer

Patent metadata

Field	Value
Publication number	US-10660912-B2
Application number	US-201515753237-A
Country	US
Kind code	B2
Filing date	Oct 5, 2015
Priority date	Oct 5, 2015
Publication date	May 26, 2020
Grant date	May 26, 2020

Abstract

Disclosed is a combination of gemcitabine-[phenyl-benzoxy-L-alaninyl)]-phosphate (chemical name: 2′-Deoxy-2′,2′-difluoro-D-cytidine-5′-O-[phenyl (benzoxy-L-alaninyl)]phosphate) (NUC-1031) and a platinum-based anticancer agent selected from carboplatin, dicycloplatin, oxaliplatin, satraplatin and nedaplatin. The combinations are useful in the treatment of cancer and particularly ovarian cancer.

First claim

The invention claimed is:

1. A method of treating cancer, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula 2:

or a pharmaceutically acceptable salt thereof, in combination with carboplatin; wherein the cancer is ovarian cancer.

2. The method of claim 1 , wherein the compound of Formula 2 comprises greater than about 90% of the diastereomer represented by Formula 3:

3. The method of claim 1 , wherein the compound of Formula 2 is a mixture of phosphate diastereoisomers.

4. The method of claim 1 , wherein the compound of Formula 2 is not in the form of a salt.

5. The method of claim 1 , wherein the compound of Formula 2 is administered intravenously.

6. The method of claim 1 , wherein the cancer is relapsed.

7. The method of claim 1 , wherein the cancer is refractory, resistant or partially resistant to carboplatin.

8. The method of claim 1 , wherein the cancer is sensitive to carboplatin.

9. The method of claim 1 , wherein the dose of the compound of Formula 2, or a pharmaceutically acceptable salt thereof administered at each administration event is between 250 mg/m 2 and 1250 mg/m 2 .

10. The method of claim 1 , wherein at each administration event the compound of Formula 2, or a pharmaceutically acceptable salt thereof, is administered in a dosage between 300 mg/m 2 and 1000 mg/m 2 .

11. The method of claim 1 , wherein at each administration event the compound of Formula 2, or a pharmaceutically acceptable salt thereof, is administered in a dosage between 400 mg/m 2 and 800 mg/m 2 .

12. The method of claim 1 , wherein at each administration event carboplatin is administered in a dosage selected to provide an AUC of between 2 and 5.5 mgmL −1 min −1 .

13. The method of claim 1 , wherein at each administration event carboplatin is administered in a dosage selected to provide an AUC of between 2.5 and 4.5 mgmL −1 min −1 .

14. The method of claim 1 , wherein the compound of Formula 2, or a pharmaceutically acceptable salt thereof, and carboplatin are administered simultaneously.

15. The method of claim 1 , wherein the compound of Formula 2, or a pharmaceutically acceptable salt thereof, are administered sequentially.

Assignees

• NuCana plc

Inventors

• Griffith Hugh

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/282

  Platinum compounds · 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

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title

• A61K31/7068 Primary

  having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid · CPC title