Abstract 686P
Background
In the context of evolving therapeutic landscape in mRCC patients (pts) promoting IO and TKI combination, predictive biomarkers of efficacy are necessary. The role of circulating angiogenesis biomarkers (CABs) to predict response to IO has been assessed in the prospective BIONIKK trial.
Methods
The multicenter randomized phase II BIONIKK clinical trial (NCT02960906) included naive mRCC pts treated according to their ccrcc molecular groups: ccrcc1&4 by either nivolumab (N) or ipilumumab + nivolumab (IN) and ccrcc2&3 to sunitinib/pazopanib or IN. VEGF-A, sVEGFR1&2, sNeuropilin-1, angiopoietin 1 and 2, PlGF, PDGF AA& BB, sVCAM1, sEndoglin, IL-8, sPDL1, CA9, MMP-9 and SDF-1 were assessed at baseline (bsl) and at 6 weeks (6w). Association of bsl levels and % change from bsl (%ch) with ccrcc groups was estimated using ANOVA/ANCOVA. Association with overall response rate (ORR) and PFS was estimated using logistic and Cox models stratified on treatment. Correlation between CAB levels and their 3’-RNAseq transcriptomic expression and FFPE IHC staining was performed using multiple factor analysis. This study was sponsored by ARTIC and supported by FONCER contre le Cancer.
Results
Out of the 200 pts randomized overall, 113 were subject to longitudinal assessment of CABs. We found significant bsl mean differences between VEGFR-TKI-sensitive tumours (ccrcc2&3, n=45) and less or poor sensitive tumours (ccrcc1&4, n=68) for angiopoietin 1, sEndoglin, sVCAM-1, VEGF-A and sNeuropilin-1 whereas %ch differed significantly for sEndoglin, sVEGFR2, sVCAM1, MMP9 and SDF-1. No CAB was associated with ORR or PFS at bsl in univariate analysis. Upon MFA, CABs were strongly correlated between each other and linked to their related gene expression levels. More results will be presented at the ESMO meeting.
Conclusions
This study revealed differences in CAB bsl and %ch levels between immunogenic ccrcc1&4 sub-groups versus ccrcc2&3. Based on these results, ongoing exploration aims to identify a predictive CAB signature of tumour response to TKI and/or IO and to decipher mechanisms that could explain differences between ccRCC sub-groups.
Clinical trial identification
NCT02960906.
Editorial acknowledgement
Legal entity responsible for the study
ARTIC.
Funding
FONCER contre le cancer.
Disclosure
All authors have declared no conflicts of interest.