Fgfr1 extracellular domain combination therapies

Abstract

Methods of treating cancer comprising administering a fibroblast growth factor receptor 1 (FGFR1) extracellular domain (ECD) and/or an FGFR1 ECD fusion molecule in combination with at least one additional therapeutic agent selected from docetaxel, paclitaxel, vincristine, carboplatin, cisplatin, oxaliplatin, doxorubicin, 5-fluorouracil (5-FU), leucovorin, pemetrexed, and bevacizumab are provided. Dosage packs comprising an FGFR1 ECD and/or an FGFR1 ECD fusion molecule and/or at least one additional therapeutic agent selected from docetaxel, paclitaxel, vincristine, carboplatin, cisplatin, oxaliplatin, doxorubicin, 5-fluorouracil (5-FU), leucovorin, pemetrexed, and bevacizumab are also provided. In some embodiments, a dosage pack comprises instructions for administering FGFR1 ECD and/or FGFR1 ECD fusion molecule with at least one additional therapeutic agent.

1 . A method of treating cancer in a subject comprising administering to the subject an effective amount of a fibroblast growth factor receptor 1 (FGFR1) extracellular domain (ECD) fusion molecule and at least one additional therapeutic agent selected from paclitaxel, carboplatin, cisplatin, oxaliplatin, doxorubicin, 5-fluorouracil (5-FU), leucovorin, pemetrexed, etoposide, a VEGF antagonist, a VEGF trap, an anti-VEGF antibody, and bevacizumab, wherein the FGFR1 ECD fusion molecule comprises an FGFR1 ECD comprising an amino acid sequence selected from SEQ ID NOs: 1 to 4 and a fusion partner, wherein administration of the FGFR1 ECD fusion molecule and the at least one additional therapeutic agent results in at least additive inhibition of tumor growth in a mouse zenograft model of the cancer. 
     
     
         2 . (canceled) 
     
     
         3 . The method of  claim 1 , wherein the at least one additional therapeutic agent is paclitaxel. 
     
     
         4 . The method of  claim 1 , wherein the at least one additional therapeutic agent is cisplatin. 
     
     
         5 . The method of  claim 1 , wherein the at least one additional therapeutic agent is pemetrexed. 
     
     
         6 . (canceled) 
     
     
         7 . The method of  claim 1 , wherein the at least one additional therapeutic agent is 5-FU. 
     
     
         8 . (canceled) 
     
     
         9 . The method of  claim 1 , wherein the method comprises administering to the subject at least two additional therapeutic agents selected from paclitaxel, carboplatin, cisplatin, oxaliplatin, doxorubicin, 5-fluorouracil (5-FU), leucovorin, pemetrexed, etoposide, a VEGF antagonist, a VEGF trap, an anti-VEGF antibody, and bevacizumab, wherein administration of the FGFR1 ECD fusion molecule and the at least two additional therapeutic agents results in at least additive inhibition of tumor growth in a mouse zenograft model of the cancer. 
     
     
         10 . The method of  claim 9 , wherein one of the at least two additional therapeutic agents is paclitaxel, oxaliplatin, 5-FU or bevacizumab. 
     
     
         11 . The method of  claim 9 , wherein the at least two additional therapeutic agents are paclitaxel and carboplatin. 
     
     
         12 . The method of  claim 9 , wherein the at least two additional therapeutic agents are oxaliplatin and 5-FU. 
     
     
         13 . The method of  claim 9 , wherein the at least two additional therapeutic agents are doxorubicin and paclitaxel. 
     
     
         14 . The method of  claim 9 , wherein the at least two additional therapeutic agents are cisplatin and etoposide. 
     
     
         15 . The method of  claim 9 , wherein the at least two additional therapeutic agents are 5-FU and leucovorin. 
     
     
         16 . The method of  claim 9 , wherein the at least two additional therapeutic agents are bevacizumab and 5-FU. 
     
     
         17 . (canceled) 
     
     
         18 . The method of  claim 1 , wherein the fusion partner is an Fc. 
     
     
         19 . The method of  claim 1 , wherein the FGFR1 ECD fusion molecule comprises a sequence selected from SEQ ID NO: 5 and SEQ ID NO: 6. 
     
     
         20 . (canceled) 
     
     
         21 . The method of  claim 1 , wherein the cancer is non-small cell lung cancer and the mouse xenograft model comprises H1703 cells, A549 cells, or NCI-H520 cells. 
     
     
         22 . The method of  claim 1 , wherein the cancer is small cell lung cancer and the mouse xenograft model comprises DMS 53 cells. 
     
     
         23 . The method of  claim 1 , wherein the cancer is breast cancer and the mouse xenograft model comprises JIMT-1 cells. 
     
     
         24 . The method of  claim 1 , wherein the cancer is colon cancer and the mouse xenograft model comprises Colo205 cells.