Fgfr2 inhibitors alone or in combination with immune stimulating agents in cancer treatment

Abstract

Provided herein are uses of fibroblast growth factor receptor 2 (FGFR2) inhibitors in cancer treatment, in some cases in combination with immune stimulating agents, such as inhibitors of PD-1 or PD-L1. In some embodiments, FGFR2 inhibitors may comprise FGFR2 antibodies or FGFR2 extracellular domain (ECD) polypeptides, or FGFR2 ECD fusion molecules comprising an FGFR2 ECD and a fusion partner. In some embodiments, PD-1/PD-L1 inhibitors may comprise anti-PD-1 antibodies such as antibodies that bind to PD-1 or to PD-L1 and inhibit interactions between these proteins, as well as PD-1 fusion proteins or polypeptides.

1 .- 130 . (canceled) 
     
     
         131 . A method of determining whether a gastric or bladder cancer patient will be responsive to treatment with a fibroblast growth factor receptor 2 (FGFR2) inhibitor comprising determining whether the gastric or bladder cancer overexpresses FGFR2-IIIb by immunohistochemistry (IHC), wherein the overexpression is determined by an IHC signal of 2+ or 3+ in at least 10% of tumor cells in a sample of the cancer. 
     
     
         132 . The method of  claim 131 , wherein the patient is determined to be responsive to FGFR2-IIIb antibody treatment if:
 a) the cancer is gastric cancer that has an immunohistochemistry (IHC) signal of 2+ or 3+ in at least 10% of tumor cells;   b) the cancer is gastric cancer that has an IHC signal of 2+ or 3+ in at least 10% of tumor cells, and wherein the FGFR2 gene is amplified;   c) the cancer is gastric cancer that has an IHC signal of 2+ or 3+ in at least 10% of tumor cells, and wherein the FGFR2 gene is not amplified;   d) the cancer is bladder cancer that has an IHC signal of 2+ or 3+ in at least 10% of tumor cells;   e) the cancer is bladder cancer that has an H score of 20 or greater;   f) the cancer is bladder cancer that has an H score of 10-19; or   g) the cancer is bladder cancer that has an H score of <10.