Association of PD-L2 expression in human tumors with atezolizumab activity.

11506 Background: Atezolizumab (atezo, MPDL3280A) is a humanized IgG1 mAb that prevents the interaction of the ligand PD-L1 with PD-1 and B7.1 and can reinvigorate anticancer T-cell responses. Atezo does not inhibit the interaction of an alternative ligand PD-L2 with PD-1. PD-L2 is associated with Th2 immune responses but its role in anticancer immunity is unclear. Here we characterize the association between these ligands and patient (pt) outcome following atezo treatment across tumor types. Methods: Expression of PD-L1 and PD-L2 transcripts in tumor specimens from pts before starting atezo treatment was assessed using Fluidigm platform or RNAseq. Pts from PCD4989g (melanoma, n = 38; RCC, n = 59), POPLAR (NSCLC, n = 112) and cohort 2 of IMvigor210 (urothelial carcinoma UC, n = 251) trials were included in the analysis. Results: A close Spearman correlation was observed for PD-L1 and PD-L2 transcripts in melanoma (0.8), UC (0.77), NSCLC (0.74) but less so in RCC (0.43). Overall survival HRs and odds ratios (ORs) of being a responder using the median expression of PD-L1 and PD-L2 across 4 cancer types are listed (Table). High expression of either ligand in these tumors was associated with improved OS benefit to atezo treatment. Neither ligand had an association with OS benefit of docetaxel (doc) in NSCLC pts. OS HR of PD-L2 high in the randomized trial (POPLAR) of atezo vs doc was 0.50 (95% CI: 0.31-0.83), favoring atezo. Conclusions: Clinical outcomes in 4 distinct cancer types showed that high expression of PD-L2 was associated with improved benefit of atezo therapy.These data show that blocking the PD-L1:PD-1 and PD-L2:B7.1 axes but not PD-L2: PD-1 axis is highly efficacious in PD-L2 high pts. Further evidence is required to understand the role of PD-L2 in cancer. Clinical efficacy of atezo monotherapy. N PD-L1 PD-L2 Events/N OS HRa 95% CI ORb Events/N OS HRa 95% CI ORb BM high BM low BM high BM low Melanoma 38 8/19 11/19 0.52 0.21-1.29 2.19 7/19 12/19 0.28 0.11-0.72 3.88 RCC 59 13/30 17/29 0.62 0.3-1.28 2.7 12/30 18/29 0.5 0.24-1.06 7 UC 251 73/126 83/125 0.76 0.55-1.04 1.9 72/126 84/125 0.73 0.54-1.01 2.13 NSCLC 112 27/56 34/56 0.72 0.44-1.2 3.18 26/56 35/56 0.61 0.37-1.02 3.18 BM, biomarker aBM high vs low bOdds ratio for response, including CR and PR per RECIST v1.1.