INHIBITING MUTANT IDH-1
Methods of treating patients diagnosed with cancer harboring an IDH-1 mutation are provided, including the therapeutic administration of a certain inhibitor of a mutant IDH-1 as a single agent, or in combination with azacitidine (AZA).
1 . Use of a pharmaceutical composition comprising Compound 1, or pharmaceutically acceptable salt thereof,
in treating a cancer harboring an isocitrate dehydrogenase-1 (IDH-1) mutation (mIDH-1) in a patient by administering a total of 300 mg of Compound 1 (or a corresponding amount in the form of a pharmaceutically acceptable salt thereof) to a patient each day during a course of treatment.
2 . The use of claim 1 , wherein a 150 mg amount of Compound 1 (or a corresponding amount in the form of a pharmaceutically acceptable salt thereof) is administered to the patient twice per day (BID) throughout the course of treatment.
3 . The use of claim 1 , wherein the cancer is a mIDH-1 form of acute myeloid leukemia.
4 . The use of claim 3 , wherein the acute myeloid leukemia is relapsed or refractory or is drug-resistant.
5 . The use of claim 1 , wherein the cancer is a mIDH-1 solid tumor.
6 . The use of claim 1 , wherein the cancer is of a mIDH-1 glioma.
7 . The use of claim 6 , wherein the mIDH-1 glioma is an advanced glioma that has recurred or progressed prior to the administration of Compound 1.
8 . The use of any one of the preceding claims, wherein the mIDH1 is a R132X mutation.
9 . The use of claim 8 , wherein the R132X mIDH-1 mutation is selected from R132L, R132G and R132S.
10 . The use of any one of the preceding claims, wherein the pharmaceutical composition comprising Compound 1 or a pharmaceutically acceptable salt thereof is orally administered to the patient.
11 . The use of any one of the preceding claims, wherein Compound 1, (or a corresponding amount in the form of a pharmaceutically acceptable salt thereof) is administered as a single agent for the treatment of the cancer harboring the IDH-1 mutation.
12 . The use of any of the preceding claims, wherein the course of treatment is at least 15 consecutive days to reach a steady state blood concentration of Compound 1 (or a corresponding amount in the form of a pharmaceutically acceptable salt thereof) in the patient.
13 . The use of any one of the preceding claims, wherein the course of treatment is at least 6 months.
14 . The use of any one of the preceding claims, wherein the pharmaceutical composition comprises Compound 1 in a Type A solid form characterized by a reflection X-ray powder diffraction (XRPD) pattern comprising characteristic peaks at 6.3, 12.8, 13.8, 23.6, and 27.8 degrees±0.2° 2θ.
15 . The use of any one of the preceding claims, wherein the pharmaceutical composition comprises the following formulation for oral administration: (a) Type A solid form of Compound 1 in a relative weight of about 33, (b) a microcrystalline cellulose in a relative weight of about 61, (c) a croscamellose sodium in a relative weight of about 5 and a magnesium stearate in a relative weight of about 1;
wherein the Type A solid form of Compound 1 is characterized by a reflection X-ray powder diffraction (XRPD) pattern comprising characteristic peaks at 6.3, 12.8, 13.8, 23.6, and 27.8 degrees±0.2° 2θ.