Treatment Regimens

Patent metadata

Field	Value
Publication number	US-2020345755-A1
Application number	US-201816642835-A
Country	US
Kind code	A1
Filing date	Aug 30, 2018
Priority date	Aug 30, 2017
Publication date	Nov 5, 2020
Grant date	—

Abstract

The invention relates to 5-fluoro-2′-deoxyuridine-5′-O-[1-naphthyl (benzoxy-L-alaninyl)] phosphate (NUC-3373), or a pharmaceutically acceptable salt thereof, for use in the treatment of cancer, in particular by intravenous infusion for a continuous period of up to 10 hours. The invention also relates to methods of treating cancer by administration of NUC-3373 to particular sub-groups of cancer patient. The invention further relates to methods for selecting a patient for treatment with NUC-3373.

First claim

1 . 5-fluoro-2′-deoxyuridine-5′-O-[1-naphthyl (benzoxy-L-alaninyl)] phosphate (NUC-3373), or a pharmaceutically acceptable salt thereof, for use in the treatment of cancer, wherein the treatment is by administration of NUC-3373 over a period of up to 10 hours.

2 . NUC-3373 for use according to claim 1 , wherein the treatment is by administration of NUC-3373 over a period of up to 5 hours.

3 . NUC-3373 for use according to claim 1 or claim 2 , wherein the treatment is by administration of NUC-3373 over a period of up to 2 hours.

4 . NUC-3373 for use according to claim 1 , wherein the treatment is by administration of NUC-3373 over a period of between 1 and 2 hours, 2 and 4 hours or 1 and 6 hours.

5 . NUC-3373 for use according to any preceding claim, wherein the administration is by means of continuous infusion.

6 . NUC-3373 for use according to claim 5 , wherein the infusion is by intravenous infusion.

7 . NUC-3373 for use according to any of the preceding claims, wherein the treatment is by administration of NUC-3373 by means of or includes a bolus administration.

8 . NUC-3373 for use according to any preceding claim, wherein the cancer is selected from the group consisting of: pancreatic cancer, breast cancer, ovarian cancer, bladder cancer, other urothelial cancers, gastrointestinal cancer (also known as cancer of the digestive tract), liver cancer, lung cancer, biliary cancer, prostate cancer, cholangiocarcinoma, renal cancer, neuroendocrine cancer, sarcoma, lymphoma, leukemia, cervical cancer, thymic cancer, a cancer of an unknown primary origin, mesothelioma, adrenal cancer, cancer of the uterus, cancer of the fallopian tube, peritoneal cancer, endometrial cancer, testicular cancer, head and neck cancer, the central nervous system cancer, basal cell carcinoma, Bowens disease, other skin cancers (such as malignant melanoma, merckel cell tumour and rare appendage tumours), ocular surface squamous neoplasia and germ cell tumours.

9 . NUC-3373 for use according to claim 8 , wherein the cancer is a gastrointestinal cancer selected from the group consisting of: oesophageal cancer, gastric cancer, stomach cancer, bowel cancer, small intestine cancer, colon cancer, appendix mucinous, goblet cell carcinoid, liver cancer, biliary cancer, gallbladder cancer, anal cancer and rectal cancer.

10 . NUC-3373 for use according to any preceding claim, wherein the patient with the cancer also suffers from hand-foot syndrome.

11 . NUC-3373 for use according to claim 10 , wherein the patient has developed hand-foot syndrome from a previous treatment regimen with a drug other than NUC-3373.

12 . NUC-3373 for use according to claim 11 , wherein the patient has developed hand-foot syndrome when being treated with 5FU, capecitabine or tegafur.

13 . 5-fluoro-2′-deoxyuridine-5-O-[1-naphthyl (benzoxy-L-alaninyl)] phosphate (NUC-3373) or a pharmaceutically acceptable salt thereof, for use in the treatment of cancer in a subject that suffers from hand-foot syndrome.

14 . NUC-3373 for use according to claim 14 , wherein the subject has developed hand-foot syndrome following treatment with a fluoropyrimidine such as 5FU, capecitabine or tegafur.

15 . NUC-3373 for use according to claim 14 or 15 , wherein the cancer is selected from the group consisting of: pancreatic cancer, breast cancer, ovarian cancer, bladder cancer, other urothelial cancers, gastrointestinal cancer (also known as cancer of the digestive tract), liver cancer, lung cancer, biliary cancer, prostate cancer, cholangiocarcinoma, renal cancer, neuroendocrine cancer, sarcoma, lymphoma, leukemia, cervical cancer, thymic cancer, a cancer of an unknown primary origin, mesothelioma, adrenal cancer, cancer of the uterus, cancer of the fallopian tube, peritoneal cancer, endometrial cancer, testicular cancer, head and neck cancer, the central nervous system cancer, basal cell carcinoma, Bowens disease, other skin cancers (such as malignant melanoma, merckel cell tumour and rare appendage tumours), ocular surface squamous neoplasia and germ cell tumours.

16 . NUC-3373 for use according to any of claims 14 to 16 , wherein the cancer is gastrointestinal cancer and is selected from the group consisting of: oesophageal cancer, gastric cancer, stomach cancer, bowel cancer, small intestine cancer, colon cancer, appendix mucinous, goblet cell carcinoid, liver cancer, biliary cancer, gallbladder cancer, anal cancer and rectal cancer.

17 . A method of selecting a subject with cancer for treatment with 5-fluoro-2′-deoxyuridine-5-O-[1-naphthyl (benzoxy-L-alaninyl)] phosphate (NUC-3373), or a pharmaceutically acceptable salt thereof, the method comprising determining whether the subject has hand-foot syndrome, wherein if the subject has hand-foot syndrome, the subject is selected for treatment with 5-fluoro-2′-deoxyuridine-5′-O-[1-naphthyl (benzoxy-L-alaninyl)] phosphate (NUC-3373).

18 . The method according to claim 18 , wherein the patient developed hand-foot syndrome whilst being treated with a fluoropyrimidine, such as 5FU or capecitabine.

19 . 5-fluoro-2′-deoxyuridine-5-O-[1-naphthyl (benzoxy-L-alaninyl)] phosphate (NUC-3373), or a pharmaceutically acceptable salt thereof, for use in the treatment of cancer in subjects that are deficient or partially deficient in dihydropyrimidine dehydrogenase (DPD).

20 . NUC-3373 for use according to claim 20 , wherein the cancer is selected from the group consisting of: pancreatic cancer, breast cancer, ovarian cancer, bladder cancer, other urothelial cancers, gastrointestinal cancer (also known as cancer of the digestive tract), liver cancer, lung cancer, biliary cancer, prostate cancer, cholangiocarcinoma, renal cancer, neuroendocrine cancer, sarcoma, lymphoma, leukemia, cervical cancer, thymic cancer, a cancer of an unknown primary origin, mesothelioma, adrenal cancer, cancer of the uterus, cancer of the fallopian tube, peritoneal cancer, endometrial cancer, testicular cancer, head and neck cancer, the central nervous system cancer, basal cell carcinoma, Bowens disease, other skin cancers (such as malignant melanoma, merckel cell tumour and rare appendage tumours), ocular surface squamous neoplasia and germ cell tumours.

21 . NUC-3373 for use according to claim 20 or 21 , wherein the cancer is gastrointestinal cancer and is selected from the group consisting of: oesophageal cancer, gastric cancer, stomach cancer, bowel cancer, small intestine cancer, colon cancer, appendix mucinous, goblet cell carcinoid, liver cancer, biliary cancer, gallbladder cancer, anal cancer and rectal cancer.

22 . NUC-3373 for use according to any one of claims 20 to 22 , wherein the subject has a genetic mutation selected from IVS14+1G>A mutation in intron 14 coupled with exon 14 deletion (known as DPYD*2A), 496A>G in exon 6; 2846A>T in exon 22; and T1679G (DPYD*13) in exon 13.

23 . NUC-3373 for use according to claim 23 , wherein the subject has the IVS14+1G>A DPYD variant (DPYD*2A) mutation.

24 . NUC-3373 for use according to any one of claims 20 to 22 , wherein the subject has previously exhibited intolerance for 5FU or capecitabine or has a family history of intolerance for 5FU or capecitabine.

25 . A method of assessing effectiveness of an anti-cancer therapy, the method comprising: assaying a sample of peripheral blood mononuclear cells (PBMCs) or cancer cells from a subject receiving an anti-cancer therapy to determine the level of intracellular deoxythymidi

Assignees

• NuCana plc

Inventors

• Griffith Hugh

Classifications

• G01N33/57595

  involving intracellular compounds · CPC title

• A61K31/7072 Primary

  having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine · CPC title

• G01N33/5011

  for testing antineoplastic activity · CPC title

• G01N2333/91017

  with definite EC number (2.1.1.-) · CPC title

• A61P35/00

  Antineoplastic agents · CPC title