Corvus Pharmaceuticals, Inc.

Andrew Hotson

Richard A Miller

Stephen Willingham

Ian Mccaffery

Po Y Ho

Lan Mccaffery

This disclosure relates to methods for detecting a level of expression of one or more genes (or proteins) in a subject having or suspected of having cancer, and optionally treating the subject with an adenosine pathway antagonist, for example an adenosine A2A receptor (ADORA2A) antagonist, to treat the cancer. The genes (or proteins) include, without limitation, CD68, CD163, LBP, CCL2, CCL3, CCL7, CCL24, CCNE1, CD 14, CD300E, CD86, CD93, CLEC5A, CSF3, CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL8, DFNA5, ECEL1, EPB41L3, EHF, FUT7, GALM, GBP6, GPR157, HAS1, IL1A, IE-1β, IL23, IL24, IL5, IL6, IL8, INHBA, LAP3, LAYN, LOC100505585, MRPL11, NID1, OST4, PADI2, PID1, PLAUR, PPBP, PTGS2, RHCG, SERPINB2, SLC11A1, SLC7A7, SPON1, ST6GALNAC2, TBX21, THBS1, C1R, C1S, C4BPA, CCL11, CCL20, CXCL16, CXCL2, HAMP, HSD11B1, IT GAM, LIF, SAA1, TFRC, TLR5, TNFSF14, TREM2, APP, ATG10, BCL2, CCL15, CD24, CD46, CD59, CREB5, CX3CL1, CXCL14, CYFIP2, DEFB1, DPP4, ECSIT, EPCAM, IFIT1, IGF1R, ITGA6, ITGB3, MAP2K4, MAPK1, MASP1, PPARG, RORC, SPA17, STAT5B, TOLLIP, AKT3, BMI1, CD 164, CD34, CDH5, CREB1, DOCK9, ENG, HMGB1, ITGA1, JAM3, MAF, MAPK3, MAPK8, MCAM, MFGE8, NOTCH1, NRP1, PRKCE, SMAD2, TAL1, THY1, TNFSF12, TRAF6, TXNIP, VEGFA, S100A8, and/or WDR830S.

Methods for detecting and treating cancers having adenosine pathway activation

This disclosure relates to methods for detecting a level of expression of one or more genes in a subject having or suspected of having cancer, and optionally treating the subject with an adenosine pathway antagonist, for example an adenosine A2A receptor (ADORA2A) antagonist in combination with a PD-1 inhibitor and/or a PD-L 1 inhibitor, to treat the cancer. The genes include, without limitation, CD68, CD 163, EBP, CCL2, CCL3, CCL7, CCL24, CCNE1, CD 14, CD300E, CD86, CD93, CLEC5A, CSF3, CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL8, DFNA5, ECEL1, EPB41L3, EHF, FUT7, GALM, GBP6, GPR157, HAS1, IL1A, IE-1β, IL23, IL24, IL5, IL6, IL8, INHBA, LAP3, LAYN, LOC100505585, MRPL11, NID1, OST4, PADI2, PID1, PLAUR, PPBP, PTGS2, RHCG, SERPINB32, SLC11A1, SLC7A7, SPON1, ST6GALNAC2, TBX21, THBS1, C1R, C1S, C4B3PA, CCL11, CCL20, CXCL16, CXCL2, HAMP, HSD11B1, IT GAM, LIF, SAA1, TFRC, TLR5, TNFSF14, TREM2, APP, ATG10, BCL2, CCL15, CD24, CD46, CD59, CREB5, CX3CL1, CXCL14, CYFIP2, DEFB1, DPP4, EC SIT, EPCAM, IFIT1, IGF1R, ITGA6, ITGB3, MAP2K4, MAPK1, MASP1, PPARG, RORC, SPA17, STAT5B, TOLLIP, AKT3, BMI1, CD 164, CD34, CDH5, CREB1, DOCK9, ENG, HMGB1, ITGA1, JAM3, MAF, MAPK3, MAPK8, MCAM, MFGE8, NOTCH1, NRP1, PRKCE, SMAD2, TAL1, THY1, TNFSF12, TRAF6, TXNIP, VEGFA, S100A8, and/or WDR83 OS.

Provided herein are, inter alia, methods of treating cancer by administering to a subject a therapeutically effective amount of an adenosine-A2A (A2A) receptor antagonist or a combination of an adenosine-A2A (A2A) receptor antagonist and a programmed cell death protein 1 (PD-1) signaling pathway inhibitor. Further provided are pharmaceutical compositions including an A2A receptor antagonist, a PD-1 signaling pathway inhibitor and a pharmaceutically acceptable excipient. Further provided are methods of detecting cellular effects, for example expression of pCREB, before, after or during adenosine receptor antagonist treatment.

Methods of treating cancer

Provided herein are, inter alia, methods of treating a cancer tumor in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an adenosine A2A receptor antagonist, wherein the subject comprises an elevated level of CD8+ tumor infiltrating lymphocytes relative to a control, the subject comprises an elevated level of T-effector gene signature relative to a control, the subject comprises an increased cancer tumor T cell receptor diversity or blood T cell receptor diversity relative to a control, the cancer tumor comprises an elevated level of PD-L1 relative to a control, and/or the cancer tumor or the blood of the subject comprises an elevated level of CD73 relative to a control. Further provided are, inter alia, methods for determining whether a subject is likely to, is, or has responded to anti-cancer therapy comprising an A2A receptor antagonist.

Provided herein are, inter alia, methods of treating cancer by administering to a subject a therapeutically effective amount of an adenosine-A2A(A2A) receptor antagonist or a combination of an adenosine-A2A(A2A) receptor antagonist and a programmed cell death protein 1(PD-1) signaling pathway inhibitor. Further provided are pharmaceutical compositions including an A2A receptor antagonist, a PD-1 signaling pathway inhibitor and a pharmaceutically acceptable excipient. Further provided are methods of detecting cellular effects, for example expression of pCREB, before, after or during adenosine receptor antagonist treatment.

Growing community of inventors

Burlingame, CA, United States of America

Andrew Hotson