Single-arm phase ib/II study of durvalumab and guadecitabine in advanced kidney cancer (NCT03308396).

TPS711Background: Checkpoint inhibitor immunotherapy directed at PD1/PDL1 has shown clinical efficacy in advanced clear cell Renal Cell Cancer (ccRCC). However, only a minority of patients respond to anti-PD1 monotherapy. There is an urgent unmet need to improve response rates including through rational combinations to reverse immune evasion by tumors. The chemokines CXCL9 and CXCL10 in the tumor micro-environment are chemo-attractants for activated NK and Th1 cells and are critical for anti-tumor immunity. Preclinical data from our group showed hypermethylation induced silencing of CXCL9/10 signaling is an important tumor immune evasion mechanism. In RCC cell lines (A-498, HTB-46 and CRL-1611), hypomethylating agents increased CXCL9/10. In mouse xenograft models, combination therapy with a hypomethylating agent and checkpoint inhibitors led to higher levels of CXCL 9/10, reversal of immune evasion and potent tumor regression. We hypothesized that the combination of guadecitabine (hypomethylating agent) w...