US 12,233,060 B2
Inhibitors of Ataxia-Telangiectasia Mutated and Rad3-related protein kinase (ATR) for use in methods of treating cancer
Christopher James Lord, London (GB); Chris Williamson, London (GB); and Samuel Jones, London (GB)
Assigned to THE INSTITUTE OF CANCER RESEARCH: ROYAL CANCER HOSPITAL, London (GB); and BREAST CANCER NOW, London (GB)
Appl. No. 16/067,994
Filed by THE INSTITUTE OF CANCER RESEARCH: ROYAL CANCER HOSPITAL, London (GB); and BREAST CANCER NOW, London (GB)
PCT Filed Jan. 6, 2017, PCT No. PCT/EP2017/050270
§ 371(c)(1), (2) Date Jul. 3, 2018,
PCT Pub. No. WO2017/118734, PCT Pub. Date Jul. 13, 2017.
Claims priority of application No. 1600388 (GB), filed on Jan. 8, 2016; and application No. 1621472 (GB), filed on Dec. 16, 2016.
Prior Publication US 2019/0008856 A1, Jan. 10, 2019
Int. Cl. A61K 31/4965 (2006.01); A61K 31/497 (2006.01); A61K 31/506 (2006.01); A61K 31/519 (2006.01); A61K 31/7105 (2006.01); A61P 35/00 (2006.01)
CPC A61K 31/497 (2013.01) [A61K 31/4965 (2013.01); A61K 31/519 (2013.01); A61K 31/7105 (2013.01); A61P 35/00 (2018.01)] 9 Claims
 
1. A method for treating an individual having cancer with an Ataxia-Telangiectasia Mutated and Rad3-related protein kinase inhibitor (ATRi), the method comprising:
(a) determining in a sample obtained from the individual whether the cancer is mutated or deficient in one or more BAF-complex genes, and
(b) selecting the individual for treatment with the ATRi where the cancer has one or more BAF-complex gene mutations or deficiencies; and
(c) administering a therapeutically effective amount of the ATRi to the individual, said ATRi eliciting one or more of premature mitotic entry, genomic instability and apoptosis in said cancer cells,
wherein said ATRi is VE-821, VE-822 (VX-970), AZ20, or AZD6738
wherein the cancer is mutated or deficient in one or more BAF-complex genes selected from ARID1A, ARID1B, SMARCA4, SMARCB1, and PBRM1,
wherein the cancer is synovial sarcoma, ovarian clear cell carcinoma, colorectal cancers, melanoma, lung cancer, hepatocellular carcinoma, gastric cancer, bladder cancer, hematologic malignancies, squamous cell carcinoma, serous ovarian cancer, breast cancer, pancreatic cancer, medulloblastoma, renal cancer or glioma,
and wherein for a cancer mutated in one or more BAF-complex genes, the mutation reduces or abolishes the expression or function of the one or more BAF-complex genes.