1700P - Impact of sarcomatoid (S) and rhabdoid (R) components (comp.) on the efficacy of nivolumab (N) +/- ipilimumab (I) in the first-line (L1) treatment of metastatic clear cell renal cell carcinoma (mRCC) in the randomized phase II BIONIKK trial

Background

The BIONIKK trial showed promising efficacy of N+/-I and TKI in L1 mRCC according to tumor molecular group. S/R comp. are associated with poor prognosis but conversely may predict the efficacy of immune checkpoint inhibitors. We report on the impact of S/R on the efficacy of L1 in the BIONIKK trial.

Methods

Patients (pts) with mRCC were randomized according to ccrcc1-4 molecular group to receive N (58), NI (101) or TKI (40) in L1. Centralized pathological review was performed to identify ISUP grade, to quantify S/R comp. and the immune infiltrate (scale 0 to 3). Endpoints were objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) according to S/R. Median follow-up was 46.6 months (IQR: 41.2-54.4).

Results

Of the 199 pts included, S, R and S+R was found in 23 (27.6%), 23 and 32 (co-presence: 58%) tumors respectively. Compared to pts with non-S/R tumors, those with S/R are more often IMDC int+poor (82%/78% vs 63%), have their tumors enriched in ccrcc1+4 (78%/69% vs 50%) and more immune infiltrates (2+3 in 87% vs 57%). Compared with pts without S, S-mRCC pts treated with N tended to have a higher rate of progressive disease (50% vs 34%), a shorter PFS (HR 1.23 [95%CI 0.68-2.22]), and a shorter OS (HR 2.56 [95%CI 1.28-5]), as did pts treated with TKI. Conversely, S-mRCC pts treated with NI had a higher ORR (68% vs. 42%), a longer PFS (HR 0.73 [95%CI 0.43-1.23]), and a similar OS (HR 1.03 [95%CI 0.52-2.04]). Compared with ISUP 4 tumors without S/R, S/R were associated with shorter PFS and OS with N or with TKI, and a higher ORR, PFS and OS with NI (table). Table: 1700P

Conclusions

Within the BIONIKK study, we confirm the high co-occurrence of S and R comp. in mRCC, as well as a poor prognosis associated with the S comp. We also confirmed the particular efficacy of NI, but not N alone in S-mRCC. Results by ccrcc group, R comp. and %S/R will be presented.

Clinical trial identification

NCT02960906.

Editorial acknowledgement

Legal entity responsible for the study

ARTIC (Association pour la Recherche en Thérapeutiques Innovantes en Cancérologie).

Funding

ARTIC, Bristol Myers Squibb.

Disclosure

Y. Vano: Financial Interests, Personal, Invited Speaker: Ipsen, BMS, MSD, Pfizer, Eisai; Financial Interests, Personal, Other, Congress and travel funding: Ipsen, MSD, Pfizer; 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, Steering Committee Member, Member of the scientific committee of the WITNESS study: Bristol Myers Squibb; Financial Interests, Institutional, Local PI: Tesaro. C. Tournigand: Non-Financial Interests, Leadership Role: GERCOR; Non-Financial Interests, Advisory Role: Fondation APHP. D. Borchiellini: Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Bristol Myer Squibb, Ipsen, Janssen, Merck, Pfizer; Financial Interests, Institutional, Advisory Board: Bayer, MSD; Financial Interests, Personal, Invited Speaker: Accord HealthCare; Financial Interests, Institutional, Local PI, Clinical Research: Astellas, AstraZeneca, Bayer, Bristol Myer Squibb, Exelixis, Infinity, Janssen, MSD, Roche, Taiho Oncology; Financial Interests, Institutional, Local PI: Aveo, Gilead, Seagen. B. Laguerre: Financial Interests, Personal, Other, ASCO GU symposium 2023 (travel and registration): Pfizer; Financial Interests, Personal, Other, honoraria: Astellas, Janssen, Pfizer, Eisai, Bayer; Financial Interests, Personal, Other, registration ASCO virtual meeting 2022: BMS; Financial Interests, Personal, Other, registration ASCO GU symposium 2022 (virtual): MSD; Financial Interests, Personal, Other, registration and travel for ASCO meeting 2023: AstraZeneca; Financial Interests, Personal, Other, registration and travel meeting ASCO GU 2024: Ipsen; Financial Interests, Personal, Other, registration virtual meeting EMOS 2023: MSD. P. Barthelemy: Financial Interests, Personal, Advisory Board: BMS, MSD, Merck, Pfizer, Ipsen, Bayer, Janssen Cilag, Astellas, Novartis, Amgen, Gilead; Financial Interests, Personal, Invited Speaker: AstraZeneca. G. Gravis: Financial Interests, Institutional, Invited Speaker: AAA, AMGEN, Astellas, BMS, Janssen, MSD, Pfizer, Ipsen, AstraZeneca, alliance Merck Pfizer, Bayer, Eisai; Financial Interests, Institutional, Advisory Board: Alliance Merck-Pfizer, BMS, Janssen, Pfizer, Ipsen, Bayer, Eisai, Gilead, AstraZeneca, AAA Novartis, MSD; Financial Interests, Personal, Other, Support for attending meetings and/or travel: BMS, AstraZeneca, Bayer, Ipsen, MSD, Pfizer, Janssen, AAA Novartis; Financial Interests, Institutional, Funding: Janssen; Financial Interests, Institutional, Coordinating PI: BMS; Non-Financial Interests, Principal Investigator: IPSEN, BMS, Merck. S. Oudard: Financial Interests, Personal, Advisory Board, consultancy, advisory role: Sanofi; Financial Interests, Personal, Invited Speaker, public speaking and advisory role: Janssen; Financial Interests, Personal, Advisory Board, advisory role and public speaking: AstraZeneca, MSD, Merck, Astellas, Ipsen, Pfizer, Roche, Genentech; Financial Interests, Personal, Advisory Board, Advisory board and public speaking: BMS, Bayer, Novartis. All other authors have declared no conflicts of interest.