Therapeutic compositions, combinations, and methods of use

Abstract

This invention relates to methods comprising administering a FAK inhibitor and an immunotherapeutic agent such as anti-PD-1 or anti-PD-L1; that are useful in the treatment of abnormal cell growth, such as cancer, in mammals, especially humans.

1 . A method for treating a human subject suffering from a disease or disorder described herein (e.g., abnormal cell growth, e.g., cancer (e.g., a cancer described herein)), comprising administering a FAK inhibitor in combination with an immunotherapeutic agent or procedure (e.g., wherein the immunotherapeutic agent is a compound that inhibits the immune checkpoint blockade pathway). 
     
     
         2 - 4 . (canceled) 
     
     
         5 . The method of  claim 1 , wherein the cancer is a mesothelioma; neurofibromatosis; e.g., neurofibromatosis type 2, neurofibromatosis type 1; renal cancer; lung cancer, non small cell lung cancer; liver cancer; thyroid cancer; ovarian; breast cancer; a nervous system tumor; schwannoma; meningioma; schwannomatosis; neuroma acoustic; adenoid cystic carcinoma; ependymoma; or ependymal tumors. 
     
     
         6 . The method of  claim 1 , wherein the cancer is mesothelioma (e.g., malignant pleural mesothelioma, e.g., surgical resectable malignant pleural mesothelioma), breast cancer (e.g., triple negative breast cancer), ovarian cancer (e.g., advanced ovarian cancer), lung cancer (e.g., non-small cell lung cancer (NSCLC), e.g., KRAS mutant NSCLC)), or a non-hematolotic malignancy. 
     
     
         7 . The method of  claim 1 , wherein the cancer is melanoma (e.g., N-Ras mutated locally advanced or metastasis malignant cutaneous melanoma), colorectal cancer (e.g., metastatic colorectal cancer), leukemia (e.g., acute myeloid leukemia), adenocarcinoma (e.g., pancreatic adenocarcinoma), or a solid tumor (e.g., locally advanced solid tumor, metastatic solid tumor, hepatocellular carcinoma). 
     
     
         8 . The method of  claim 1 , wherein the FAK inhibitor is administered orally. 
     
     
         9 . The method of  claim 8 , wherein the FAK inhibitor is VS-4718, VS-5095, VS-6062, VS-6063, BI 853520, or GSK2256098. 
     
     
         10 . The method of  claim 9 , wherein the FAK inhibitor is VS-4718. 
     
     
         11 . The method of  claim 9 , wherein the FAK inhibitor is VS-6063. 
     
     
         12 - 20 . (canceled) 
     
     
         21 . The method of  claim 1 , wherein the immunotherapeutic agent is an anti-CTLA-4 antibody (e.g., ipilimumab, tremelimumab). 
     
     
         22 . The method of  claim 1 , wherein the immunotherapeutic agent is an anti-PD-1 ligand (e.g., PD-LI (e.g., B7-HI or CD274); or PD-L2 (e.g., B7-DC or CD273)). 
     
     
         23 . The method of  claim 1 , wherein the immunotherapeutic agent is an anti-PD-1 antibody (e.g., anti-PD-1 or anti-PD-L1, e.g., nivolumab (i.e., MDX-1106, BMS-936558, ONO-4538); CT-011; AMP-224; pembrolizumab; pidilizumab; or MK-3475). 
     
     
         24 . The method of  claim 1 , wherein the immunotherapeutic agent is an anti-PD-L1 antibody (e.g., BMS936559 (i.e., MDX-1105); MEDI4736; MSB0010718C (avelumab); or MPDL-3280A). 
     
     
         25 . The method of  claim 1 , wherein the immunotherapeutic agent is a checkpoint blocking antibody (e.g., IMP321, MGA271). 
     
     
         26 . The method of  claim 1 , wherein the immunotherapeutic agent is an anti-CTLA-4 antibody (e.g., ipilimumab, tremelimumab, anti-TIM3, anti-LAG3, anti-TIGIT). 
     
     
         27 . The method of  claim 1 , wherein the immunotherapeutic agent is a cell-based therapy. 
     
     
         28 . The method of  claim 27 , wherein the cell-based therapy is a CAR-T therapy. 
     
     
         29 . The method of  claim 1 , wherein the immunotherapeutic agent is a co-stimulatory antibody (e.g., anti-4-1BB, anti-OX40, anti-GITR, anti-CD27, anti-CD40). 
     
     
         30 . The method of  claim 1 , further comprising administering an additional chemotherapeutic agent or radiation therapy. 
     
     
         31 . The method of  claim 1 , further comprising administering a cytotoxic agent. 
     
     
         32 . The method of  claim 31 , wherein the cytotoxic agent is gemcitabine or paclitaxel (e.g., nab-paclitaxel). 
     
     
         33 - 42 . (canceled)