Combination therapies of HDAC inhibitors and PD-1 inhibitors
Provided herein are combinations that include an HDACi and a PD-1 inhibitor that are useful for treating cancer, including reducing and/or preventing cancer metastasis. The combination is also useful for treating cancer that has been previously treated with a PD-L1 inhibitor.
1. A method for treating melanoma in an immune checkpoint inhibitor treatment-naïve human subject having melanoma, comprising administering to the immune checkpoint inhibitor treatment-naïve human subject having melanoma a therapeutically effective amount of a combination comprising an intravenously administered intravenous composition comprising a PD-1 antibody and an orally administered oral composition comprising 20 mg to 40 mg of a histone deacetylase (HDAC) inhibitor, wherein the HDAC inhibitor is HBI-8000:
2. The method of claim 1 , wherein the oral composition comprising the HDAC inhibitor comprises about 30 mg of HBI-8000.
3. The method of claim 1 , wherein the composition comprising the PD-1 antibody comprises one or more of nivolumab, pembrolizumab, pidilizumab, REGN2810 (also known as SAR-439684), PDR 001, SHR-1210 or MEDI0680.
4. The method of claim 3 , wherein the intravenous composition comprising the PD-1 antibody comprises nivolumab.
5. The method of claim 1 , wherein the oral composition comprising the HDAC inhibitor is orally administered to the subject having melanoma twice weekly (BIW).
6. The method of claim 1 , wherein the oral composition comprising HBI-8000 is administered to the subject having melanoma at a dose of 30 mg of HBI-8000 twice weekly (BIW).
7. The method of claim 1 , wherein the oral composition comprising the HDAC inhibitor comprises 20 mg, 30 mg, or 40 mg of HBI-8000.
8. The method of claim 1 , wherein the human subject having melanoma achieves a complete response.
9. The method of claim 1 , wherein the human subject having melanoma achieves a partial response.
10. A method for causing a partial response or a complete response in an immune checkpoint inhibitor treatment-naïve human subject having melanoma, comprising administering to the immune checkpoint inhibitor treatment-naïve human subject having melanoma a therapeutically effective amount of a combination comprising an intravenously administered intravenous composition comprising a PD-1 antibody and an orally administered oral composition comprising 20 mg to 40 mg of a histone deacetylase (HDAC) inhibitor, wherein the HDAC inhibitor is HBI-8000:
and wherein administering the combination to the subject causes a complete response or a partial response in the human subject.
11. The method of claim 10 , wherein the oral composition comprising the HDAC inhibitor comprises about 30 mg of HBI-8000.
12. The method of claim 10 , wherein the composition comprising the PD- 1 antibody comprises one or more of nivolumab, pembrolizumab, pidilizumab, REGN2810 (also known as SAR-439684), PDR 001, SHR-1210 or MEDI0680.
13. The method of claim 12 , wherein the intravenous composition comprising the PD-1 antibody comprises nivolumab.
14. The method of claim 10 , wherein the oral composition comprising the HDAC inhibitor is orally administered to the subject having melanoma twice weekly (BIW).
15. The method of claim 10 , wherein the oral composition comprising HBI-8000 is administered to the subject having melanoma at a dose of 30 mg of HBI-8000 twice weekly (BIW).
16. The method of claim 10 , wherein the oral composition comprising the HDAC inhibitor comprises 20 mg, 30 mg, or 40 mg of HBI-8000.
17. The method of claim 10 , wherein administering the combination to the subject causes a complete response in the human subject.
18. the method of claim 10 , wherein administering the combination to the subject causes a partial response in the human subject.