LBA87 - Phase II LITESPARK-003 study of belzutifan in combination with cabozantinib for advanced clear cell renal cell carcinoma (ccRCC)

Background

Initial results from the phase 2 LITESPARK-003 (NCT03634540) study showed promising antitumor activity for belzutifan plus cabozantinib as first-line (cohort 1) and subsequent-line (cohort 2) treatment for patients (pts) with advanced ccRCC. We present updated results from cohorts 1 and 2.

Methods

Eligible pts had advanced ccRCC and ECOG PS of 0 or 1. Cohort 1 included pts with no prior systemic therapy for advanced RCC. Cohort 2 included pts who had received prior immunotherapy and ≤2 systemic regimens for advanced RCC. All pts received oral belzutifan 120 mg and oral cabozantinib 60 mg once daily. The primary end point was ORR per RECIST v1.1 by investigator assessment. Secondary end points included DOR, PFS, OS, and safety.

Results

A total of 50 pts were enrolled in cohort 1 and 52 pts in cohort 2. Most (n = 28; 56%) pts in cohort 1 had IMDC favorable risk and most (n = 41; 79%) in cohort 2 had IMDC intermediate/poor risk. Median follow-up was 24.3 mo (range, 4.1-48.2) in cohort 1 and 39.8 mo (range, 33.1-55.0) in cohort 2. ORR is shown in the Table. Median DOR was 28.6 mo (range, 1.9+ to 35.8) in cohort 1 and 31.5 mo (range, 4.2+ to 36.8) in cohort 2. An estimated 57% of all responders in cohort 1 and 51% in cohort 2 remained in response for ≥24 mo. Median PFS was 30.3 mo (95% CI, 16-not reached [NR]) in cohort 1 and 13.8 mo (95% CI, 9-19) in cohort 2. Median OS was NR (95% CI, NR-NR) in cohort 1 and 26.7 mo (95% CI, 20-41) in cohort 2. Overall, 23 (46%) pts in cohort 1 and 33 (63%) in cohort 2 had a grade 3-5 treatment-related AE (TRAE). No pts died due to a TRAE in cohort 1 and 1 pt (2%) died due to a TRAE (respiratory failure) in cohort 2.

Conclusions

In this updated analysis of LITESPARK-003, belzutifan plus cabozantinib showed durable antitumor activity and a safety profile consistent with prior observations. These results further support the combination of an HIF-2α inhibitor and VEGFR-TKI as a potential treatment option for advanced ccRCC in both the first- and subsequent-line settings. Table: LBA87

Clinical trial identification

NCT03634540, August 16, 2018.

Editorial acknowledgement

Medical writing and/or editorial assistance was provided by Mallory Campbell and Robert Steger of ApotheCom (Yardley, PA). This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

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, 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, 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, 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. T. Bauer: Financial Interests, Personal and Institutional, Advisory Board: Pfizer, Bayer; Financial Interests, Personal and Institutional, Research Grant: Pfizer, Eli Lilly, Bayer; Financial Interests, Personal and Institutional, Principal Investigator: Pfizer, Eli Lilly, Bayer; Financial Interests, Personal and Institutional, Speaker, Consultant, Advisor: Eli Lilly. J.R. Merchan: Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Institutional, Funding: Merck, EISAI, Genentech, Exelixis, Vyriad, Imugene; Financial Interests, Institutional, Principal Investigator: Merck, EISAI, Genentech, Exelixis, Vyriad, Imugene, Seattle Genetics, Trishula Therapeutics, Corvus Pharmaceuticals, Rubius Therapeutics, Peloton Therapeutics, Sillajen; Financial Interests, Institutional, Research Funding: Sillajen. D.F. McDermott: Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Funding: Merck. M.D. Michaelson: Financial Interests, Personal, Advisory Board: Merck, EISAI, Exelixis, Janssen. E. Heath: Financial Interests, Personal, Advisory Board: Astellas Pharma, Bayer, Sanofi; Financial Interests, Personal, Other, Travel: Astellas Pharma, Caris Life Sciences, Seattle Genetics; Financial Interests, Personal, Research Funding: Astellas Pharma, Arvinas, AstraZeneca, BioXcel Therapeutics, Bristol-Myers Squibb, Calibr, Calithera Biosciences Inc., Caris Life Sciences, Corcept Therapeutics, Corvis Pharmaceuticals, Daiichi Sankyo Inc., Eisai Inc., Exelixis, Five Prime Therapeutics, Fortis Therapeutics, GSK, Gilead Sciences Inc., Harpoon Therapeutics, Hoffman-La Roche, Infinity Pharmaceuticals, iTeos Therapeutics, Janssen Research & Development LLC, Merck Sharp & Dohme, Merck, Mirati Therapeutics, Modra Pharmaceuticals, Novartis, Oncolys BioPharma, Peloton Therapeutics Inc., Pfizer, Pharmacyclics LLC, POINT Biopharma, Seattle Genetics; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Bayer, Sanofi, Seattle Genetics; Financial Interests, Personal, Steering Committee Member: Janssen Research & Development LLC; Financial Interests, Personal, Speaker, Consultant, Advisor: Sanofi; Financial Interests, Personal, Officer, Travel: Sanof. S. Zhao: Financial Interests, Personal, Other, Honoraria: Targeted Oncology; Financial Interests, Personal, Advisory Board: AstraZeneca, Janssen; Financial Interests, Personal, Writing Engagement: Novartis; Financial Interests, Institutional, Funding: Pfizer, Merck, AstraZeneca. L. Mhamdi: Financial Interests, Personal, Full or part-time Employment: Merck. R. Perini: Financial Interests, Personal, Full or part-time Employment: Merck. D. Vickery: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks or ownership: Merck. S. Tykodi: Financial Interests, Personal, Other, Honoraria: FirstWord Pharma, Targeted Oncology; Financial Interests, Personal, Officer, Honoraria: Cancer Network; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Institutional, Funding: Bristol Myers Squibb, Merck, Pfizer, Nektar Therapeutics, Exelixis, Aveo, Iovance Biotherapeutics. All other authors have declared no conflicts of interest.