1451MO - In-situ immune markers predict nivolumab (N) +/-ipilimumab (I) efficacy in frontline metastatic clear cell renal cell carcinoma (mccRCC): Key ancillary analyses from the BIONIKK randomized trial

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Clinical trial identification

NCT02960906.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Bristol Myers Squibb, ARTIC.

Disclosure

M. Bennamoun: Financial Interests, Invited Speaker: Janssen, AstraZeneca, Ipsen, Astellas. C.M. Chevreau: Financial Interests, Personal, Advisory Board: Ipsen, BMS, LEO, MSD; Financial Interests, Institutional, Invited Speaker, only for overhead: MSD, Ipsen, Karyopharm, Exelisis. D. Borchiellini: Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Bayer, Bristol Myer Squibb, Ipsen, Janssen, Merck, Pfizer; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Invited Speaker, Clinical Research: Astellas, AstraZeneca, Bayer, Bristol Myer Squibb, Exelixis, Infinity, Janssen, MSD, Roche, Taiho Oncology. P. Barthelemy: Financial Interests, Personal, Advisory Board: BMS, MSD, Merck, Pfizer, Ipsen, Bayer, Janssen Cilag, Astellas, Novartis, AMGEN; Financial Interests, Personal, Invited Speaker: AstraZeneca, Seagen. M. Gross Goupil: Financial Interests, Advisory Board: BMS, MSD, Ipsen, Pfizer; Financial Interests, Invited Speaker: BMS, MSD, Ipsen, Pfizer; Financial Interests, Sponsor/Funding: Ipsen, Janssen. C. Tournigand: Financial Interests, Invited Speaker: MSD, BMS; Financial Interests, Sponsor/Funding: MSD. S. Oudard: Financial Interests, Invited Speaker: BMS, Pfizer. Y. Vano: Financial Interests, Personal, Advisory Board: Ipsen, BMS, MSD, Pfizer, Novartis, Merck; Financial Interests, Institutional, Funding, Funding support for the CABIR study: Ipsen; Financial Interests, Institutional, Funding, Funding support for the BIONIKK study: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker, Member of the scientific committee of the WITNESS study: Bristol Myers Squibb. All other authors have declared no conflicts of interest.