Immune modulation with tlr9 agonists for cancer treatment

Abstract

The present invention relates to methods for treating a tumor, including a metastatic tumor, with TLR9 agonist in combination with an immune checkpoint inhibitor therapy.

1 .- 31 . (canceled) 
     
     
         32 . A method for treating melanoma in a patient comprising: intratumorally administering an initial dose of IMO-2125 to the melanoma patient in Week 1 of a treatment; and administering an initial dose of an immune checkpoint inhibitor that targets CTLA-4, PD-1, PD-L1, and/or PD-L2 to the patient beginning in at least Week 2 of the treatment after the initial IMO-2125 dose;
 wherein the patient is unresponsive to, is partially responsive to, is refractory to, or became resistant to a checkpoint inhibitor therapy.   
     
     
         33 . The method of  claim 32 , wherein the checkpoint inhibitor therapy is one or more of anti-CTLA-4 immunotherapy, anti-PD-1 immunotherapy, anti-PD-L1 immunotherapy, and anti-PD-L2 immunotherapy. 
     
     
         34 . The method of  claim 33 , wherein the checkpoint inhibitor therapy is one or more of ipilimumab, tremelimumab, pembrolizumab, and nivolumab. 
     
     
         35 . The method of  claim 32 , wherein the melanoma of the patient has progressed after or during treatment with one or more of anti-CTLA-4 immunotherapy, anti-PD-1 immunotherapy, anti-PD-L1 immunotherapy, and anti-PD-L2 immunotherapy. 
     
     
         36 . The method of  claim 35 , wherein the patient having melanoma has progressed after or during treatment with one or more of ipilimumab, tremelimumab, pembrolizumab, and nivolumab. 
     
     
         37 . The method of  claim 32 , wherein the patient has shown no response to the checkpoint inhibitor therapy for at least about 12 weeks. 
     
     
         38 . The method of  claim 37 , wherein the checkpoint inhibitor is one or more of anti-CTLA-4 immunotherapy, anti-PD-1 immunotherapy, anti-PD-L1 immunotherapy, and anti-PD-L2 immunotherapy. 
     
     
         39 . The method of  claim 38 , wherein wherein the checkpoint inhibitor therapy is one or more of ipilimumab, tremelimumab, pembrolizumab, and nivolumab. 
     
     
         40 . The method of  claim 32 , wherein the initial dose of immune checkpoint inhibitor therapy is administered to the patient having melanoma beginning at about Week 2, Week 3, or Week 4. 
     
     
         41 . The method of  claim 32 , wherein the melanoma is a primary cancer or a metastatic cancer. 
     
     
         42 . The method of  claim 32 , wherein the initial IMO-2125 dose is about 4 mg to about 64 mg. 
     
     
         43 . The method of  claim 32 , wherein at least two additional doses of IMO-2125 are administered intratumorally to the patient having melanoma following the initial IMO-2125 dose. 
     
     
         44 . The method of  claim 43 , wherein about 3 to about 12 doses of IMO-2125 total are administered intratumorally to the patient having melanoma. 
     
     
         45 . The method of  claim 43 , wherein the at least two additional doses of IMO-2125 are administered intratumorally at about 4 mg to about 64 mg. 
     
     
         46 . The method of  claim 45 , wherein the IMO-2125 is administered at a dose of from 4 to 64 mg per dose in weeks 1, 2, 3, 5, 8, and 11. 
     
     
         47 . The method of  claim 32 , wherein the initial dose of immune checkpoint inhibitor therapy is administered at a dose of about 0.1 mg/kg to about 5 mg/kg. 
     
     
         48 . The method of  claim 32 , wherein at least one additional dose of the immune checkpoint inhibitor therapy is administered to the patient following the initial dose of immune checkpoint inhibitor therapy. 
     
     
         49 . The method of  claim 48 , wherein about 2 to 6 doses of immune checkpoint inhibitor therapy are administered to the patient. 
     
     
         50 . The method of  claim 48 , wherein the at least one additional dose of immune checkpoint inhibitor therapy is administered at a dose of about 0.1 mg/kg to about 5 mg/kg. 
     
     
         51 . The method of  claim 32 , further comprising administering an initial dose of an IDO-1 inhibitor to the patient having melanoma beginning at about one week after the initial IMO-2125 dose. 
     
     
         52 . The method of  claim 51 , wherein the IDO-1 inhibitor is Epacadostat. 
     
     
         53 . The method of  claim 51 , wherein the IDO-1 inhibitor is administered at from 25 mg to 300 mg orally about twice daily.