Combinations of PD-1 antagonists and benzo [b] thiophene STING agonists for cancer treatment
Therapeutic combinations that comprise at least one antagonist of the Programmed Death 1 receptor (PD-1) and at least one benzo[b]thiophene compound that activates the Stimulator of Interferon Genes (STING) pathway are disclosed herein. Also disclosed is the use of such therapeutic combinations for the treatment of cancers.
1. A method of treating cancer, said method comprising administering to a subject in need thereof a combination therapy that comprises
a) a PD-1 antagonist; and
b) a benzo[b]thiophene STING agonist; wherein
the PD-1 antagonist is administered once every 21 days; and
the benzo[b]thiophene STING agonist is administered once every 3 to 28 days; and
the benzo[b]thiophene STING agonist is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
2. The method according to claim 1 , wherein the cancer occurs as one or more solid tumors or lymphomas.
3. The method according to claim 1 , wherein the cancer is selected from the group consisting of advanced or metastatic solid tumors and lymphomas.
4. The method according to claim 1 , wherein the cancer is selected from the group consisting of malignant melanoma, head and neck squamous cell carcinoma, breast adenocarcinoma, and lymphoma.
5. The method according to claim 2 , wherein the lymphoma is selected from the group consisting of diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, small lymphocytic lymphoma, mediastinal large B-cell lymphoma, splenic marginal zone B-cell lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (malt), nodal marginal zone B-cell lymphoma, lymphoplasmacytic lymphoma, primary effusion lymphoma, Burkitt lymphoma, anaplastic large cell lymphoma (primary cutaneous type), anaplastic large cell lymphoma (systemic type), peripheral T-cell lymphoma, angioimmunoblastic T-cell lymphoma, adult T-cell lymphoma, nasal type extranodal NK/T-cell lymphoma, enteropathy-associated T-cell lymphoma, gamma/delta hepatosplenic T-cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, mycosis fungoides, and Hodgkin lymphoma.
6. The method according to claim 1 , wherein the cancer has metastasized.
7. The method according to claim 1 , wherein the PD-1 antagonist is an anti-PD-1 monoclonal antibody.
8. The method according to claim 7 , wherein the PD-1 antagonist is selected from the group consisting of nivolumab, pembrolizumab, pidilizumab, and AMP-224.
9. The method according to claim 8 , wherein the PD-1 antagonist is nivolumab.
10. The method according to claim 8 , wherein the PD-1 antagonist is pembrolizumab.
11. The method of claim 1 , wherein the PD-1 antagonist is administered by intravenous infusion, and the benzo[b]thiophene STING agonist is administered orally, by intravenous infusion, by intertumoral injection or by subcutaneous injection.