US 12,440,487 B2
Method of normalizing the neutrophil to lymphocyte ratio in cancer patients with a selective glucocorticoid receptor antagonist
Andrew Greenstein, Menlo Park, CA (US); Lawrence Lu, Menlo Park, CA (US); Joseph Custodio, Menlo Park, CA (US); and Stacie Shepherd, Menlo Park, CA (US)
Assigned to Corcept Therapeutics Incorporated, Redwood City, CA (US)
Appl. No. 17/768,844
Filed by Corcept Therapeutics Incorporated, Menlo Park, CA (US)
PCT Filed Oct. 14, 2020, PCT No. PCT/US2020/055498
§ 371(c)(1), (2) Date Apr. 13, 2022,
PCT Pub. No. WO2021/076565, PCT Pub. Date Apr. 22, 2021.
Claims priority of provisional application 62/915,865, filed on Oct. 16, 2019.
Prior Publication US 2024/0156807 A1, May 16, 2024
Int. Cl. A61K 31/4745 (2006.01); A61K 45/06 (2006.01); A61P 35/00 (2006.01)
CPC A61K 31/4745 (2013.01) [A61K 45/06 (2013.01); A61P 35/00 (2018.01)] 8 Claims
 
1. A method of reducing the neutrophil-to-lymphocyte ratio (NLR) by at least 10% as compared to the baseline NLR in a cancer patient suffering from pancreatic cancer, ovarian cancer, or having an advanced solid tumor or metastatic tumor and having a baseline NLR greater than 3, said baseline NLR being determined from a blood sample obtained from said patient prior to administration of a cancer treatment to the patient;
Wherein NLR is determined by a) measuring the absolute neutrophil count obtained from a blood sample obtained from said cancer patient to determine a value of said absolute neutrophil count, b) measuring the absolute lymphocyte count obtained from said blood sample obtained from said cancer patient to determine a value of said absolute neutrophil count, and c) dividing the value of said absolute neutrophil count by the value of said absolute lymphocyte count, wherein NLR is the quotient resulting from said dividing;
the method comprising:
administering an effective amount of the nonsteroidal selective glucocorticoid receptor antagonist (GRA) relacorilant, (R)-(1-(4-fluorophenyl)-6-((1-methyl-1H-pyrazol-4-yl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(4-(trifluoromethyl)pyridin-2-yl)methanone, which has the structure:

OG Complex Work Unit Chemistry
and
administering an effective amount of a cancer treatment comprising a taxane chemotherapeutic, to said cancer patient,
whereby the NLR of said cancer patient determined after administration of relacorilant and said cancer treatment is reduced by at least 10% as compared to the baseline NLR.