Combination therapies of HDAC inhibitors and PD-L1 inhibitors
Provided herein are combinations that include an HDACi and a PD-L1 inhibitor that are useful for treating cancer, including cancer resistant to PD-1 inhibitors.
1. A method for treating colorectal cancer in a subject, comprising administering to the subject a therapeutically effective amount of a histone deacetylase inhibitor (HDAC inhibitor) in combination with a PD-L1 antibody, and the HDAC inhibitor is a compound of formula Ia:
2. The method of claim 1 , wherein the subject is treatment naive.
3. The method of claim 1 , wherein the subject is immune checkpoint treatment naive.
4. The method of claim 1 , wherein the HDAC inhibitor is administered in combination with the PD-L1 antibody as a first line therapy.
5. The method of claim 1 , wherein the HDAC inhibitor is administered in combination with the PD-L1 antibody as a second, third, fourth, fifth, or sixth line of treatment.
6. The method of claim 1 , wherein the subject has been treated with at least one anti-cancer therapy or anti-cancer agent.
7. The method of claim 1 , wherein the subject has received at least one anti-cancer therapy, which is chemotherapy, radiotherapy, surgery, targeted therapy, immunotherapy, or a combination thereof.
8. The method of claim 1 , wherein the cancer is resistant or refractory to treatment with at least one anti-cancer agent.
9. The method of claim 1 , wherein the PD-L1 antibody is durvalumab, avelumab, atezolizumab, BMS-936559, STI-A1010, STI-A1011, STI-A1012, STI-A1013, STI-A1014, or STI-A1015.
10. The method of claim 1 , wherein the PD-L1 antibody is durvalumab, avelumab, atezolizumab, or BMS-936559.
11. A pharmaceutical composition comprising an HDAC inhibitor and a PD-L1 antibody, wherein the HDAC inhibitor is a compound of formula Ia:
12. A kit comprising an HDAC inhibitor and a PD-L1 antibody, wherein the HDAC inhibitor is a compound of formula Ia: