Abstract
The randomized phase II BIONIKK trial (NCT02960906) has recently suggested that ccrcc molecular grouping could enhance response rate to N, NI and VEGFR-TKI in patients (pts) with frontline mRCC. We further identified biomarkers of N+/-I efficacy in a comprehensive translational research program characterizing in-situ immune markers. Archived paraffin-embedded (FFPE) tumor tissue samples were collected for all pts within the BIONIKK trial and centrally reviewed by an expert pathologist (VV). Using immunohistochemistry, we quantified main immune populations including T cells (CD3), B cells (CD20), tertiary lymphoid structures (TLS), and markers of immune activation (PD-1/ki67). Outcomes were objective response rate (ORR), progression-free survival (mPFS) evaluated by investigator (RECIST1.1) and early progression, defined by progression events occurring before 6 months. 160/199 mRCC pts participating in the BIONIKK trial had available FFPE samples (N:42, NI: 84, TKI: 34). In N-treated patients, TLS>2 was associated with higher ORR (73% vs 15%, p<0.01), longer mPFS (not reached (IC95%: 8.0-NE months) vs 2.4 months (IC95%: 2.3-8 months), p=0.015) and less early progressions (18% vs 63%, p=0.03). In pts treated with NI, TLS>2 correlated with response (71% vs 40%, p=0.02); higher densities of Ki67+PD1+ cells were associated with longer mPFS (16.3 months, IC95%: 10.9-NE, vs 8.25 months (IC95% 4.8-13.8 months, p=0.015), and lower events of early progressions (16% vs 41%, p=0.04). By combining TLS (>2) and Ki67/PD1 (>median) we identified pts with both high response rates (80% vs 43% p<0.01) and lower early progression events (5% vs 36%, p=0.02). A comprehensive in-situ and circulating markers analysis will be available at meeting time. We report from a randomized biomarker driven clinical trial that the number of TLS and ki67+PD1+ density likely predict N and NI efficacy in frontline mccRCC pts and that a composite score allows identification of patients with improved outcomes in NI.
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