1892P - A pooled meta-analysis of salvage nivolumab/ipilimumab (N+I) after nivolumab (N) in patients with advanced renal cell carcinoma (RCC)

Background

N+I has demonstrated improved survival for patients with treatment-naïve advanced clear cell RCC. A series of phase 2 trials (OMNIVORE NCT03203473; HCRN GU16-260 NCT03117309; TITAN-RCC NCT02917772) evaluated N+I in patients lacking an objective response to N. We performed a pooled meta-analysis of these studies to better inform the activity of N+I after N.

Methods

Key baseline characteristics and outcomes were collected and analyzed centrally. The primary endpoint was confirmed objective response rate (ORR) to N+I as defined by investigator assessed RECIST v.1. Secondary endpoints included ORR to N, progression-free survival (PFS) rate from N+I start (only for OMNIVORE and HCRN GU-16-260), and overall survival (OS) rate from N start.

Results

The analysis included 448 patients of whom 410 (91.5%) had clear cell RCC, 369 (82.3%) had IMDC intermediate/poor risk disease, and 139 (31.0%) had prior treatment. The 16-18-week ORR to N prior to N+I was 21.9% (n=98) and best ORR to N was 24.1% (n=108). 249 (55.6%) patients treated with N received N+I at a median of 16 weeks (9-21 IQR) after initiation of N [26.1% (n=65) with stable disease (SD) to N and 73.9% (n=184) with progressive disease (PD) to N]. The ORR to N+I was 12.9% (n=32) (Table). Median follow-up was 34.2 months. 6-month PFS on N+I was 39% (95% CI 30-49). 3-year OS was 57% (95% CI 52-62) from N start.

Table: 1892P

ORR to N+I

Conclusions

A small subset of patients lacking a response to N monotherapy derive benefit from salvage N+I. Additional correlative studies are warranted to investigate markers associated with benefit to N+I post N.

Clinical trial identification

NCT03203473, NCT03117309, NCT02917772.

Editorial acknowledgement

Legal entity responsible for the study

Dana Farber Cancer Institute, Georgetown Lombardi Comprehensive Cancer Center, Universitätsklinikum Jena.

Funding

BMS.

Disclosure

R.R. McKay: Financial Interests, Personal, Advisory Board: Aveo, AstraZeneca, Bayer, Calithera, Dendreon, Exelixis, JNJ, Merck, Pfizer, Sanofi, Tempus, BMS, Lilly, Sanofi, SeaGen, Telix, Sorrento Therapeutics; Financial Interests, Personal, Other, Molecular tumor board: Caris; Financial Interests, Personal, Other, Consultant: Dendreon, Myovant; Financial Interests, Personal, Invited Speaker: Exelixis, Merck, Novartis, Pfizer; Financial Interests, Steering Committee Member: Aveo, Merck, Eli Lilly; Financial Interests, Local PI: JNJ, SeaGen, Calibr, Poseida, Oncternal, Scholar Rock, Merck, Xencor, Genentech, Eli Lilly, BMS; Financial Interests, Trial Chair: Bayer, AstraZeneca; Financial Interests, Institutional, Local PI: Exelixis. D.A. Braun: Financial Interests, Personal, Invited Speaker, Speaker on innovation in oncology and clinical trial design: LM Education/Exchange Services; Financial Interests, Personal, Other, Consulting: Octane Global, Defined Health, ADepartment Field Solutions, Slingshot Insights, Blueprint Partnerships, Charles River Associates, Trinity Group, Insight Strategy, Catenion, PWW Consulting, Haymarket; Financial Interests, Personal, Advisory Board, Advisory Board: Exelixis, AVEO; Financial Interests, Personal, Invited Speaker: Aptitude Health, AbbVie; Non-Financial Interests, Advisory Role: BMS. M. Grimm: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Ipsen Pharma, Merck Serono, MSD, Pfizer, EUSA, Janssen, Oncinfo; Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, BMS, EUSA Pharma, Ipsen Pharma, Merck Serono, MSD, Pfizer, Roche, Eisai, Takeda, Ingress Health, Janssen Cilag; Financial Interests, Personal, Member of Board of Directors: Deutsche Gesellschaft für Urologie; Financial Interests, Personal and Institutional, Coordinating PI: BMS; Financial Interests, Institutional, Local PI: Intuitive Surgical; Financial Interests, Institutional, Coordinating PI: Bayer. T.K. Choueiri: Financial Interests, Personal, Advisory Board, Advice on GU/RCC drugs: BMS, Pfizer, Merck, Exelixis, AstraZeneca; Financial Interests, Personal, Advisory Board, Advice on Onc drugs: Lilly, EMD Serono, Infinity; Financial Interests, Personal, Advisory Board, Advice on RCC drug: Calithera; Financial Interests, Personal, Invited Speaker, RCC drug: Ipsen; Financial Interests, Personal, Advisory Board, Advice on GU Onc drugs: Surface Oncology; Financial Interests, Personal, Other, Consultant on onc drugs: Analysis Group; Financial Interests, Personal, Invited Speaker, CME, ww2.peerview.com: Peerview; Financial Interests, Personal, Invited Speaker, CME, gotoper.com: PER; Financial Interests, Personal, Invited Speaker, CME, researchtopractice.com: ResearchToPractice; Financial Interests, Personal, Invited Speaker, National Association of Managed Care: NAMC; Financial Interests, Personal, Invited Speaker, ASCO-related event: ASCO-SITC; Financial Interests, Personal, Other, Grant review to Orien Network ($400): ORIEN; Financial Interests, Personal, Advisory Board, Advising oncology strategy: Aptitude Health; Financial Interests, Personal, Invited Speaker, Best of ASCO19 talk: Advent health; Financial Interests, Personal, Invited Speaker, Best of ESMO20 talk ($1000): UAE Society of Onc; Financial Interests, Personal, Invited Speaker, CME, mjhlifesciences.com (OncLive): MJH life sciences; Financial Interests, Personal, Invited Speaker, Grand Rounds: MDACC; Financial Interests, Personal, Invited Speaker, RCC webinar: Cancernet; Financial Interests, Personal, Invited Speaker, CME, Kidney Cancer Association ($1300): France Foundation; Financial Interests, Personal, Invited Speaker, CME, RCC: Springer, WebMed; Financial Interests, Personal, Invited Speaker, CME, ImmunoOncology in RCC: ASiM, CE; Financial Interests, Personal, Invited Speaker, CME, PodCast in RCC ($500.00): Caribou Publishing; Financial Interests, Personal, Invited Speaker, Reimbursement ($432.00): Kidney Cancer Association; Financial Interests, Personal, Other, member of the DSMB for clinical trial: Aravive; Financial Interests, Personal, Other, on the DMC of clinical trial: Aravive; Financial Interests, Personal, Advisory Board, GU cancer drug development: alkermes, Gilead; Financial Interests, Personal, Member of Board of Directors, unpaidhttps://www.accru.org/main/public/index.xhtml: ACCRU; Financial Interests, Personal, Member of Board of Directors, Unpaidhttps://kidneycan.org: KidneyCan; Financial Interests, Personal, Other, External Advisory Board Member: Gustave Roussy; Financial Interests, Personal, Stocks/Shares: Pionyr (not publicly traded), Tempest (publicly traded), Osel (not publicly traded), Nuscan (not publicly traded), CURESPONSE; Financial Interests, Personal, Royalties, For writing and updating chapters in GU Oncology: Up-To-Date online textbook; Financial Interests, Institutional, Funding, National Chair: BMS, Merck, Exelixis, Takeda, AstraZeneca, Tracon, Peloton; Financial Interests, Institutional, Local PI: Roche, Surface Oncology, GSK; Financial Interests, Institutional, Funding, National co-chair: Pfizer, EMD-Serono; Financial Interests, Institutional, Funding, Chair of trial: Lilly; Financial Interests, Institutional, Funding, SC member: Eisai; Financial Interests, Institutional, Funding, National co-chair on 3 ongoing trials: ALLIANCE Cooperative Group; Financial Interests, Institutional, Research Grant, for GU oncology translational research through IION program: BMS; Financial Interests, Institutional, Research Grant, for GU oncology translational research: Exelixis; Financial Interests, Institutional, Research Grant, For Health outcomes research: Roche; Financial Interests, Institutional, Local PI, leads trials as PI: Nikang; Non-Financial Interests, Leadership Role, Co-Chair of the meeting, 2019-: Kidney Cancer Research Summit of KidneyCAN; Non-Financial Interests, Principal Investigator, Trial Global and National PI with GU Cancers, mostly Kidney Cancer: Multiple Academic and Industry entities; Non-Financial Interests, Personal, Other, Track Leader/Session chair/Speaker/Discussant: ASCO; Non-Financial Interests, Personal, Other, Speaker/Discussant/Track Leader: ESMO; Non-Financial Interests, Institutional, Other, Access to genomic database: Foundation Med, Guardant, Invitae; Non-Financial Interests, Member: ASCO, AACR; Non-Financial Interests, Personal, Other, Grants reviewers: AACR; Non-Financial Interests, Personal, Other, Reviewer of papers: Various journals (e.g. NEJM, Lancet, JCO); Non-Financial Interests, Personal, Other, Medical writing and editorial assistance support (e.g. ClinicalThinking, Envision Pharma Group, Fishawack Group of Companies, Health Interactions, Parexel, Oxford PharmaGenesis, and others). However, first draft frequently initiated by myself when I am 1st author: Medical Communication; Non-Financial Interests, Other, Political vote usually as “independent”, not a member of any political party. I am an issue voter: General US Politics; Other, Other, Employee at DFCI. Please see https://www.dana-farber.org/ for mission statement (non-profit hospital). I am also the past President of Medical Staff at DFCI 2015-2018: Dana-Farber Cancer Institute (DFCI); Other, Other, Professor at HMS, please see https://hms.harvard.edu/ for mission statement (non-profit school): Harvard Medical School (HMS); Other, Other, No financial interest. Institutional. Filed patents related to biomarkers of immune checkpoint blockers and circulating free methylated DNA. No money made and some patents were abandoned: Filed patents. All other authors have declared no conflicts of interest.