...using an immunocompetent orthotopic lung adenocarcinoma mouse model we find that treatment with DRP-104 increases survival of Keap1 mutant tumor....DRP-104 impairs nucleotide synthesis in KEAP1 mutant tumors and thereby inhibits cancer cell growth...we find that DRP-104 impairs the growth of KEAP1 mutant tumors through both targeting of tumor intrinsic metabolic vulnerabilities and through tumor extrinsic immunostimulatory mechanisms such as promoting the expansion of functional anti-tumor T cell populations.

Here we show DRP-104 is potent in reducing KEAP1 mutant tumor growth in both murine and patient derived LUAD and squamous tumor models. Our data suggests that DRP-104 is a promising therapy to treat KEAP1 mutant lung cancers and may offer further therapeutic potential when combined with standard of care or other novel metabolic strategies.