BET inhibitors as a treatment for myelofibrosis
The present disclosure provides methods, pharmaceutical compositions, and kits for treating cancer in patients in need thereof. The methods comprise administering to a patient in need a BET (bromodomain and extra-terminal protein) inhibitor, or a pharmaceutically acceptable salt thereof, alone or in combination with one or more JAK inhibitors. Also provided are medicaments for use in treating cancer.
1. A method of treating myelofibrosis in a subject in need thereof, the method comprising orally administering to the subject:
a compound of formula (I):
or a pharmaceutically acceptable salt thereof; and
a compound of formula (II):
or a pharmaceutically acceptable salt and/or solvate thereof;
wherein the compound of formula (I), or the pharmaceutically acceptable salt thereof, is administered at a daily dose of 0.25 mg, 0.5 mg, 0.75 mg, or 1.0 ma on a five days on, two days off schedule for three weeks, and wherein the compound of formula (II), or the pharmaceutically acceptable salt and/or solvate thereof, is administered at a daily dose of about 400 mg.
2. The method of claim 1 , wherein the compound of formula (I), or the pharmaceutically acceptable salt thereof, and the compound of formula (II), or the pharmaceutically acceptable salt and/or solvate thereof, are administered concurrently.
3. The method of claim 1 , wherein the compound of formula (I), or the pharmaceutically acceptable salt thereof, and the compound of formula (II), or the pharmaceutically acceptable salt and/or solvate thereof, are administered sequentially.
4. The method of claim 1 , wherein the compound of formula (II) or a pharmaceutically acceptable salt and/or hydrate thereof is administered.
5. The method of claim 1 , wherein the dihydrochloride monohydrate of the compound of formula (II) is administered.
6. The method of claim 1 , wherein the myelofibrosis is relapsed/refractory myelofibrosis.
7. The method of claim 1 , wherein the subject is treatment naïve.
8. The method of claim 1 , wherein the subject has previously been treated with ruxolitinib.
9. The method of claim 1 , wherein the myelofibrosis is primary myelofibrosis.
10. The method of claim 9 , wherein the primary myelofibrosis is selected from intermediate risk primary myelofibrosis and high risk primary myelofibrosis.
11. The method of claim 1 , wherein the myelofibrosis is secondary myelofibrosis.
12. The method of claim 1 , wherein the myelofibrosis is post-essential thrombocythemia myelofibrosis.
13. The method of claim 1 , wherein the myelofibrosis is post-polycythemia vera myelofibrosis.