Treatments of prostate cancer with combinations of abiraterone acetate and niraparib

Abstract

The present disclosure relates to a combination of abiraterone acetate and niraparib, free-dose and fixed-dose combinations of abiraterone acetate and niraparib, and methods of treatment of prostate cancer with said combinations.

1 - 39 . (canceled) 
     
     
         40 . A method for the treatment of mCSPC in a male human patient, said method comprising administering to the patient an effective amount of a pharmaceutical formulation comprising abiraterone acetate and niraparib tosylate monohydrate, plus prednisone. 
     
     
         41 . The method of  claim 40 , wherein the mCSPC is deleterious germline or somatic homologous recombination repair (HRR) gene-mutated mCSPC. 
     
     
         42 . The method of  claim 41 , wherein the deleterious germline or somatic HRR gene mutation is in one or more genes, including without being limited to, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, PALB2, RAD51B, and RAD54L. 
     
     
         43 . The method of  claim 40 , wherein the patient has undergone androgen deprivation therapy (ADT) prior to the treatment with the pharmaceutical formulation, plus prednisone. 
     
     
         44 . The method of  claim 43 , wherein said ADT is a medical or surgical castration. 
     
     
         45 . The method of  claim 43 , wherein said ADT is started within 6 months prior to the treatment with the pharmaceutical formulation, plus prednisone. 
     
     
         46 . The method of  claim 43 , wherein said ADT is started within at least 14 days prior to the treatment with the pharmaceutical formulation, plus prednisone. 
     
     
         47 . The method of  claim 43 , wherein said ADT started no more than 90 days prior to the treatment with the pharmaceutical formulation, plus prednisone; and wherein said ADT is abiraterone acetate. 
     
     
         48 . The method of  claim 43 , wherein the patient undergoes ADT during the treatment with the pharmaceutical formulation, plus prednisone. 
     
     
         49 . The method of  claim 40 , wherein the patient has not undergone prior therapy with a next generation androgen signaling inhibitor therapy. 
     
     
         50 . The method of  claim 49 , wherein said next generation androgen signaling inhibitor therapy is selected from abiraterone acetate, enzalutamide, apalutamide, darolutamide, nilutamide, flutamide, bicalutamide, and the like. 
     
     
         51 . The method of  claim 40 , wherein the patient has received docetaxel or cabazitaxel prior to the treatment with the pharmaceutical formulation, plus prednisone. 
     
     
         52 . The method of  claim 40 , wherein the patient has received radiation or surgical intervention, prior to the treatment with the pharmaceutical formulation, plus prednisone. 
     
     
         53 . The method of  claim 40 , wherein the patient has received abiraterone acetate plus prednisone, prior to the treatment with the pharmaceutical formulation plus prednisone. 
     
     
         54 . The method of  claim 53 , wherein the patient has received abiraterone acetate plus prednisone, during a month prior to the treatment with the pharmaceutical formulation plus prednisone. 
     
     
         55 . The method of  claim 40 , wherein the patient has received treatments for localized prostate cancer, prior to the treatment with the pharmaceutical formulation plus prednisone. 
     
     
         56 . The method of  claim 55 , wherein said treatments for localized prostate cancer have been completed at least 1 year prior to the treatment with the pharmaceutical formulation plus prednisone. 
     
     
         57 . The method of  claim 55 , wherein said treatments for localized prostate cancer are up to 3 years of ADT including radiation therapy, prostatectomy, lymph node dissection, or systemic therapies. 
     
     
         58 . The method of  claim 40 , wherein said pharmaceutical formulation is a free-dose combination (FrDC) of abiraterone acetate and niraparib; or a FrDC of abiraterone acetate and niraparib tosylate monohydrate. 
     
     
         59 . The method of  claim 40 , wherein said pharmaceutical formulation is a fixed-dose combination (FDC) comprising abiraterone acetate and niraparib; or a FDC comprising abiraterone acetate and niraparib tosylate monohydrate. 
     
     
         60 . The method of  claim 58 , wherein the FrDC or FDC comprise, each independently, about 50 mg niraparib eq. and about 500 mg abiraterone acetate; about 100 mg niraparib eq. and about 500 mg abiraterone acetate; about 50 mg niraparib eq. and about 375 mg abiraterone acetate; about 100 mg niraparib eq. and about 375 mg abiraterone acetate; about 50 mg niraparib eq. and about 250 mg abiraterone acetate; about 100 mg niraparib eq. and about 250 mg abiraterone acetate; about 33 mg niraparib eq. and about 333 mg abiraterone acetate; or about 67 mg niraparib eq. and about 333 mg abiraterone acetate. 
     
     
         61 . The method of  claim 58 , wherein the FrDC or FDC are oral dosage forms. 
     
     
         62 . The method of  claim 61 , wherein the oral dosage form is a tablet, a capsule, or a sachet. 
     
     
         63 . The method of  claim 40 , wherein said pharmaceutical formulation is a fixed-dose combination (FDC) as defined in any one of Tables 1-12.