A method of treating a patient suffering from adrenocortical carcinoma (ACC), said patient having an ACC tumor or tumors, the amount of said ACC tumor or tumors being the ACC tumor load of the patient, the patient having cortisol excess, and having lower expression of the gene ZNF683 in said ACC tumor or tumors as compared to ZNF683 expression in ACC tumors in patients who suffer from ACC without cortisol excess, the method comprising:
- Identifying a patient
- a) suffering from adrenocortical carcinoma (ACC),
- b) suffering from cortisol excess, and
- c) having lower expression of the gene ZNF683 as compared to ZNF683 expression in patients without cortisol excess who suffer from ACC;
- administering to said patient a combination treatment comprising administration of
- 1) a selective glucocorticoid receptor modulator (SGRM),
- wherein said SGRM is a heteroaryl-ketone fused azadecalin compound having the formula:
- wherein
- R1 is a heteroaryl ring having from 5 to 6 ring members and from 1 to 4 heteroatoms each independently selected from the group consisting of N, O and S, optionally substituted with 1 to 4 R1a groups each independently selected from R1a;
- each R1a is independently selected from the group consisting of hydrogen, C1-6 alkyl, halogen, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, CN, N-oxide, C3-8 cycloalkyl, and C3-8 heterocycloalkyl;
- ring J is selected from the group consisting of a cycloalkyl ring, a heterocycloalkyl ring, an aryl ring and a heteroaryl ring, wherein the heterocycloalkyl and heteroaryl rings have from 5 to 6 ring members and from 1 to 4 heteroatoms each independently selected from the group consisting of N, O and S;
- each R2 is independently selected from the group consisting of hydrogen, C1-6 alkyl, halogen, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkyl-C1-6 alkoxy, CN, OH, NR2aR2b, C(O)R2a, C(O)OR2a, C(O)NR2aR2b, SR2a, S(O)R2a, S(O)2R2a, C3-8 cycloalkyl, and C3-8 heterocycloalkyl, wherein the heterocycloalkyl groups are optionally substituted with 1-4 R2c groups;
- alternatively, two R2 groups linked to the same carbon are combined to form an oxo group (═O);
- alternatively, two R2 groups are combined to form a heterocycloalkyl ring having from 5 to 6 ring members and from 1 to 3 heteroatoms each independently selected from the group consisting of N, O and S, wherein the heterocycloalkyl ring is optionally substituted with from 1 to 3 R2d groups;
- R2a and R2b are each independently selected from the group consisting of hydrogen and C1-6 alkyl;
- each R2c is independently selected from the group consisting of hydrogen, halogen, hydroxy, C1-6 alkoxy, C1-6 haloalkoxy, CN, and NR2aR2b;
- each R2d is independently selected from the group consisting of hydrogen and C1-6 alkyl, or two R2d groups attached to the same ring atom are combined to form (═O);
- R3 is selected from the group consisting of phenyl and pyridyl, each optionally substituted with 1-4 R3a groups;
- each R3a is independently selected from the group consisting of hydrogen, halogen, and C1-6 haloalkyl;
- and
- subscript n is an integer from 0 to 3;
- or salts and isomers thereof,
- and
- 2) An antibody checkpoint inhibitor
- to said identified patient;
- thereby achieving a better treatment outcome from said identified patient than would be achieved by treatment with an antibody checkpoint inhibitor alone, wherein said treatment outcome is selected from a) reduction in said patient's ACC tumor load, b) restoration of T-cell and natural killer (NK) cell signaling pathways in the patient, c) increased T-cell and NK cell infiltration into the ACC in the patient, and d) reduced neutrophil infiltration into the ACC in the patient.