1702P - Updated results of phase II study of cabozantinib (Cabo) with nivolumab (Nivo) and ipilimumab (Ipi) in advanced renal cell carcinoma with divergent histologies (RCCdh)

Background

We report updated results on treatment intensification with the combination of Cabo/Nivo/Ipi in patients (pts) with metastatic RCCdh in a multi-institutional prospective single arm phase II trial. (NCT04413123).

Methods

Eligible pts had metastatic RCCdh with ECOG performance status of 0-1 who received up to one line of prior therapy excluding immunotherapy or Cabo. Pts underwent a baseline biopsy and received treatment with Nivo 3 mg/kg and Ipi 1 mg/kg intravenously Q3 weeks (W) for 4 cycles followed by Nivo 480 mg IV Q4W. Cabo was given continuously at dose of 40 mg daily; reductions to 20 mg daily and 20 mg every other day were allowed. The primary endpoint was objective response rate (ORR) by RECIST 1.1. Safety was a secondary endpoint.

Results

At the time of data cut-off (Feb 15 2024), 39 pts received at least 1 study drug and were included in the analysis. 13% (n=5) pts received prior systemic therapy. Median follow-up was 18.4 (range, 4.6-38.5) months. Objective response was achieved in 8 pts (ORR 21%, two-sided 80% CI, 12%-31%) all of whom were treatment-naïve; one pt has unconfirmed complete response at time of analysis. 23% of pts experienced progressive disease as best response. Median duration of response for the 8 responders was 13.7 months; 75% (6/8) maintained response greater than 9 months. 8 patients remain on therapy; 4 of these patients have ongoing shrinkage with stable disease. Median progression free survival was 9.7 months (95% CI: 6.1-12.7). Median overall survival was not reached; OS rate at 18 months was 66% (95% CI: 47%-80%). There were no new toxicity signals; 77% (n=30) developed treatment-related grade 3 or higher toxicities; 49% (n=19) required high dose steroids (prednisone ≥ 40 mg daily or equivalent). 21% (n=8) discontinued all study drugs due to toxicity. No grade 5 toxicity has been reported.

Conclusions

With extended followup, the study continues to suggest activity for the combination in patients with RCCdh though with significant toxicity. An additional cohort of 20 pts has been enrolled with Cabo starting dose of 20 mg daily. Genomics and PDL1 analysis will be presented.

Clinical trial identification

NCT04413123.

Editorial acknowledgement

Legal entity responsible for the study

Dana Farber Cancer Institute.

Funding

BMS, Exelixis.

Disclosure

B.A. McGregor: Financial Interests, Personal, Advisory Board: Exelixis, BMS, Dendreon, Seagen, Astellas, Eisai, Pfizer, Gilead, Arcus, Loxo/Lily; Financial Interests, Personal, Invited Speaker: EMD Serono, Seagen; Financial Interests, Institutional, Trial Chair: Pfizer, Exelixis, Exelixis, BMS, Gilead; Financial Interests, Institutional, Local PI: Calithera, Seagen, Aveo; Non-Financial Interests, Member: ASCO. W. Xu: Financial Interests, Personal, Advisory Board: Exelixis, Xencor, Jazz; Financial Interests, Personal, Other, Consulting: Aveo, Merck; Financial Interests, Institutional, Research Grant, Research funding paid to institution: Oncohost; Financial Interests, Institutional, Local PI: CRISPR Therapeutics. M.A. Bilen: Financial Interests, Personal, Advisory Board: Exelixis, Bayer, BMS, Eisai, Pfizer, AstraZeneca, Janssen, Calithera Biosciences, Nektar, EMD Serono, Seagen, Sanofi; Financial Interests, Institutional, Local PI: Merck, Xencor, Bayer, Bristol Myers Squibb, Genentech/Roche, Seagen, Incyte, Nektar, AstraZeneca, Tricon Pharmaceuticals, Genome & Company, AAA, Peloton Therapeutics, Pfizer. 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, Adept 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, ASCO Post RCC Roundtable, Targeted Oncology, Pfizer, Medscape; Financial Interests, Personal, Other, Advisor: Fortress Biotech (subsidiary), DLA Piper; Financial Interests, Personal, Other, Co-Founder: CurIOS; Financial Interests, Personal, Advisory Board: Elephas Bio, Merck, Eisai, Compugen, Link Cell Therapies, Scholar Rock, Neomorph; Financial Interests, Personal, Other, Medical education: Accolade 2nd.MD; Financial Interests, Personal, Other, stock options: Elephas; Financial Interests, Personal, Research Grant: AstraZeneca, Exelixis; Non-Financial Interests, Advisory Role: Bristol Myers Squibb; Non-Financial Interests, Member: ASCO. S. Berg: Financial Interests, Personal, Advisory Board: Pfizer, Exelixis. T. Zhang: Financial Interests, Personal, Advisory Board: Merck, Exelixis, Sanofi-Aventis, Janssen, AstraZeneca, Pfizer, Amgen, BMS, Pharmacyclics, Seagen, QED Therapeutics, Eisai, Aveo, Bayer, Eli Lilly, Gilead, Novartis, EMD Serono; Financial Interests, Personal, Other, Consulting: MJH Associates, Vanaiam, Aptitude Health, PeerView, Clinical Care Options; Financial Interests, Institutional, Local PI: Novartis, Abbvie, AstraZeneca, Pfizer, Astellas, Eli Lilly, Tempus, ALX Oncology, Janux Therapeutics, OncoC4; Financial Interests, Institutional, Steering Committee Member: Merck; Financial Interests, Institutional, Coordinating PI: Janssen, Exelixis; Non-Financial Interests, Advisory Role, Medical Steering Committee: Kidney Cancer Association; Non-Financial Interests, Advisory Role, Scientific Advisory Board: KCCure; Non-Financial Interests, Advisory Role: Myrovlytis Trust. 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, Eisai, Blue Earth Diagnostics; 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.F. McDermott: Financial Interests, Personal, Advisory Board: Pfizer, Merck, BMS, Alkermes, Iovance, werewolf therapeutics, Calithera, Eisai; Financial Interests, Personal, Advisory Board, Scientific Advisory Board Members: Cullinan; Financial Interests, Institutional, Coordinating PI: BMS. H. Hammers: Financial Interests, Personal and Institutional, Advisory Board: BMS, Merck, Surface Oncology; Financial Interests, Personal, Advisory Board: Pfizer, Exelixis, Bayer, Novartis, ARMO Biosciences, Corvus, Lily; Financial Interests, Institutional, Advisory Board: Aravive, NGM Biopharmaceuticals. 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; 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Financial Interests, Personal, Advisory Board, GU cancer drug development: alkermes, Gilead; Financial Interests, Personal, Other, Study section reviewer. $200.00 per day for 1 day: National Cancer Institute; Financial Interests, Personal, Other, Cancer Center Grand Rounds: Cleveland Clinic; Financial Interests, Personal, Advisory Board, Advisory Board/month: CURESPONSE; Financial Interests, Personal, Advisory Board: Tempest, Precede Bio (not publicly traded)); 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, advisor: Pionyr (not publicly traded), Tempest (publicly traded), Osel (not publicly traded), Precede Bio (not publicly traded)), CURESPONSE (not publicly traded), Inndura; Financial Interests, Personal, Stocks/Shares: Primium; 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, AstraZeneca, Takeda, Tracon; Financial Interests, Institutional, Local PI, National Chair: Roche; Financial Interests, Institutional, Funding, National co-chair: Pfizer, EMD-Serono; Financial Interests, Institutional, Funding, Chair of trial: Lilly; Financial Interests, Institutional, Local PI: Surface Oncology, GSK; 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- current and BOD member (unpaid): 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, 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, Pharmagenesis, and others). However, first draft frequently initiated by myself when I am 1st author: Medical Communication; Non-Financial Interests, Member: ASCO, AACR; 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, 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, Professor at HMS, Please see https://hms.harvard.edu/ for mission statement (non-profit school): Harvard Medical School (HMS); Other, The institution filed patents related to biomarkers of immune checkpoint blockers, and circulating tumor DNA. No money made and some patents were abandoned: Filed patents. All other authors have declared no conflicts of interest.