INHIBITING MUTANT ISOCITRATE DEHYDROGENASE 1 (mIDH-1)
Patients diagnosed with a cancer harboring an IDH-1 mutation can be treated by the administration of a therapeutically effective amount of a pharmaceutical composition comprising Compound 1, a selective inhibitor of 2-HG production from mIDH-1 enzymes including the R132 mutations R132C, R132H, R132L, R132G, and R132S.
1 - 20 . (canceled)
21 . A method of treating an adult patient with acute myeloid leukemia having a susceptible IDH1 mutation as detected by an FDA-approved test, comprising the step of administering to the patient in need thereof 150 mg of olutasidenib twice daily.
22 . The method of claim 21 , wherein the olutasidenib is orally administered to the patient.
23 . The method of claim 22 , wherein the olutasidenib is administered as a Type A solid form.
24 . The method of claim 23 , wherein the olutasidenib is administered in a 150 mg strength unit dosage form.
25 . The method of claim 21 , wherein the susceptible IDH1 mutation is a R132X mIDH-1 mutation.
26 . The method of claim 21 , wherein the patient meets the following inclusion criteria:
a. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2;
b. no prior solid organ allograft;
c. liver function characterized by bilirubin≤2 times upper limit of normal (ULN) (≤3 times ULN in patients with Gilbert Syndrome), and aspartate transaminase (AST, also referred to as SGOT), alanine transaminase (ALT, also referred to as SGPT) and alkaline phosphatase (ALP) 3 times ULN;
d. renal function characterized by a serum creatinine≤1.5 times ULN or calculated creatinine clearance≥50 mL/min;
e. recovery from the non-hematologic toxic effects of prior treatment to Grade≤1, or baseline value according to NCI CTCAE classification (excluding infertility, alopecia, or Grade 1 neuropathy); and
f. baseline QTcF≤450 msec (average of the QTcF values of screening triplicate ECGs) for patients without a bundle branch block (BBB).
27 . A method of treating a transfusion-dependent adult patient with acute myeloid leukemia having a susceptible IDH1 mutation as detected by an FDA-approved test, comprising the step of administering to the patient in need thereof 150 mg of olutasidenib twice daily.
28 . The method of claim 27 , wherein the olutasidenib is orally administered to the patient.
29 . The method of claim 28 , wherein the olutasidenib is administered as a Type A solid form.
30 . The method of claim 29 , wherein the olutasidenib is administered in a 150 mg strength unit dosage form.
31 . The method of claim 27 , wherein the susceptible IDH1 mutation is a R132X mIDH-1 mutation.
32 . The method of claim 27 , wherein the patient meets the following inclusion criteria:
a. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2;
b. no prior solid organ allograft;
c. liver function characterized by bilirubin≤2 times upper limit of normal (ULN) (≤3 times ULN in patients with Gilbert Syndrome), and aspartate transaminase (AST, also referred to as SGOT), alanine transaminase (ALT, also referred to as SGPT) and alkaline phosphatase (ALP) 3 times ULN;
d. renal function characterized by a serum creatinine≤1.5 times ULN or calculated creatinine clearance≥50 mL/min;
e. recovery from the non-hematologic toxic effects of prior treatment to Grade≤1, or baseline value according to NCI CTCAE classification (excluding infertility, alopecia, or Grade 1 neuropathy); and
f. baseline QTcF≤450 msec (average of the QTcF values of screening triplicate ECGs) for patients without a bundle branch block (BBB).