Compounds and compositions for treating hematological disorders
The present invention provides methods of treating hematological disorders and solid malignant tumors, using substituted indazole compounds and pharmaceutically acceptable salts thereof. The compounds inhibit IRAK4 and BCL-2 kinases.
1. A method of treating Diffuse Large B-cell Lymphoma (DLBCL) in a subject, comprising administering to the subject compound A and venetoclax, wherein compound A is:
2. The method of claim 1 , wherein the subject has a L265P mutation in MYD88.
3. The method of claim 1 , wherein the DLBCL is activated B-cell subtype DLBCL.
4. The method of claim 1 , wherein conjointly administering compound A and venetoclax provides improved efficacy relative to separately administering compound A or venetoclax.
5. The method of claim 4 , wherein conjointly administering compound A and venetoclax provides a synergistic effect, as compared to the administration of compound A or venetoclax alone.
6. The method of claim 1 , wherein the compound A and venetoclax are administered simultaneously.
7. The method claim 1 , wherein the venetoclax is administered within about 5 minutes to within about 168 hours prior to or after administration of compound A.