1449MO - Updated efficacy of lenvatinib (LEN) + pembrolizumab (PEMBRO) vs sunitinib (SUN) in patients (pts) with advanced renal cell carcinoma (aRCC) in the CLEAR study

Background

The phase 3 CLEAR study showed statistically significant PFS (primary endpoint) and OS benefits, and improved ORR with LEN + PEMBRO vs SUN in pts with aRCC in the 1L setting. We report updated efficacy and describe pts who completed 2 years of PEMBRO and continued on LEN monotherapy.

Methods

Pts with aRCC and no prior systemic therapy were randomized (1:1:1) to receive LEN 20 mg PO QD + PEMBRO 200 mg IV Q3W; LEN 18 mg + EVE 5 mg PO QD; or SUN 50 mg PO QD (4 weeks on/2 weeks off). Randomization was stratified by geographic region and MSKCC prognostic group. In this descriptive follow-up analysis (data cutoff March 31, 2021), we report updated PFS, ORR, and duration of response (DOR) as assessed by independent imaging review per RECIST v1.1 for LEN + PEMBRO and SUN, as well as an exploratory subgroup analysis of pts who completed 2 yrs of PEMBRO per protocol and continued LEN. Updated OS was previously reported.

Results

Updated efficacy results are in the table. Median survival follow-up was 33.7 mos for pts randomized to LEN + PEMBRO (N = 355) and 33.4 mos for pts randomized to SUN (N = 357). PFS (median 23.3 vs 9.2 mos) and ORR (71.0% vs 36.1%) continued to be improved with LEN + PEMBRO vs SUN. DOR was longer with LEN + PEMBRO vs SUN (median, 26.0 vs 14.7 mos). Of the pts who completed 2 yrs of PEMBRO (n = 101 of 355 pts), most (n = 65) had IMDC intermediate/poor risk disease and fewer (n = 36) had favorable risk disease, consistent with the intention-to-treat population. PEMBRO completers had a 36-mos OS rate of 94.5%; 69 (68.3%) of these pts had treatment-related treatment-emergent adverse events. Table: 1449MO

^aPreviously reported.CR, complete response; DOR, duration of response; NE, not estimable.

Conclusions

With longer follow-up, LEN + PEMBRO continued to show a clinically meaningful benefit vs SUN, consistent with prior results of the CLEAR study. A large proportion of pts treated with LEN + PEMBRO completed 2 yrs of PEMBRO and continued with LEN monotherapy with ongoing clinical benefit. The results further support LEN + PEMBRO as a standard of care in 1L aRCC.

Clinical trial identification

NCT02811861.

Editorial acknowledgement

Medical writing support was provided by Irene Minkina, PhD, of Oxford PharmaGenesis Inc., Newtown, PA, USA, with funding by Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Legal entity responsible for the study

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

Funding

This study was sponsored by Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

C.G. Porta: Financial Interests, Personal, Invited Speaker: Angelini Pharma, AstraZeneca, BMS, Eisai, General Electric, Ipsen, Merck, MSD; Financial Interests, Personal, Speaker’s Bureau: Angelini Pharma, BMS, Eisai, Ipsen, Merck, MSD, Angelini Pharma, AstraZeneca, BMS, Eisai, Ipsen, Merck, MSD; Financial Interests, Personal, Advisory Role: Angelini Pharma, AstraZeneca, BMS, Eisai, Ipsen, Merck, MSD; Financial Interests, Personal, Other, Protocol Steering Committee Member: BMS, Eisai, EUSA Pharma, MSD. M. Eto: Financial Interests, Personal, Other, Speaker’s Bureau: MSD, ONO, Takeda, Merck; Financial Interests, Personal, Research Grant: Sanofi, ONO, Takeda. R.J. Motzer: Financial Interests, Personal, Advisory Board: Pfizer, Novartis, Eisai, Exelixis, Merck, Genentech/Roche, Incyte, Lilly Oncology, AstraZeneca, EMD Serono, Aveo Pharmaceuticals, AVEO; Financial Interests, Institutional, Invited Speaker, funding for trial conduct from sponsor to my employer MSKCC: Pfizer, Eisai, Genentech/Roche, Merck, Bristol Myers Squibb, Exelixis, AVEO. U.F.F. De Giorgi: Financial Interests, Personal, Advisory Board: Pfizer, BMS, MSD, PharmaMar, Astellas, Bayer, Ipsen, Novartis, EISAI, Janssen; Financial Interests, Personal, Invited Speaker: Roche, BMS, Clovis Oncology, AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca, Sanofi, Roche. T. Buchler: Financial Interests, Personal, Invited Speaker: Roche, Bayer, Bristol Myers Squibb, Astellas, Janssen, Ipsen, Merck; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Ipsen, Merck, Servier, Eli Lilly, Pfizer; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb, Merck, Bayer, Exelixis, Eisai, Eli Lilly, MSD; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Research Grant: Servier, Roche; Non-Financial Interests, Advisory Role: Leram Pharmaceuticals. N.S. Basappa: Financial Interests, Personal, Advisory Board: Merck, Eisai, Ipsen, Pfizer, BMS, AstraZeneca, Bayer, Seagen, Janssen, EMD Serono, Roche; Financial Interests, Personal, Sponsor/Funding: Eisai; Financial Interests, Personal, Advisory Role: Janssen, Ipsen. M.J. Mendez Vidal: Financial Interests, Personal, Speaker’s Bureau: Astellas Pharma, Bristol Myers Squibb, Ipsen, EUSA Pharma, Janssen-Cilag, Pfizer, Roche; Financial Interests, Personal, Advisory Role: Astellas Pharma, Bristol Myers Squibb, EUSA Pharma, Ipsen, Eisai, Janssen-Cilag, Novartis, Pfizer, Roche, Sanofi. S. Tjulandin: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Eli Lilly, BioCad, Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca, R-Pharm, Merck Sharp Dohme, Roche, Pierre Fabre, Servier; Financial Interests, Personal, Ownership Interest: RusPharmTech; Financial Interests, Personal and Institutional, Invited Speaker: Merck Sharp Dohme, Eisai, AbbVie, Novartis, Bristol Myers Squibb; Other, The Chair: Russian Society of Clinical Oncology (RUSSCO). B. Melichar: Financial Interests, Personal, Invited Speaker: Roche, Pfizer, BMS, Astellas, Novartis, Bayer, MSD, Merck Serono, Sanofi, Servier, AstraZeneca, Amgen, Janssen, Eisai, Eli Lilly, Pierre Farbre; Financial Interests, Personal, Advisory Role: Roche, Pfizer, BMS, Astellas, Novartis, Bayer, MSD, Merck Serono, Sanofi, Servier, AstraZeneca, Amgen, Janssen, Eisai, Eli Lilly, Pierre Farbre. T.E. Hutson: Financial Interests, Personal, Speaker’s Bureau: Astellas Pharma, Bristol Myers Squibb, Eisai, Exelixis, Johnson & Johnson, Pfizer; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, Eisai, Exelixis, Johnson & Johnson, Pfizer; Financial Interests, Personal, Advisory Role: Astellas Pharma, Bayer/Onyx, Bristol Myers Squibb, Exelixis, Johnson & Johnson, Novartis, Pfizer. C. Alemany: Financial Interests, Personal, Speaker’s Bureau: Alexion, Bristol Myers Squibb; Non-Financial Interests, Institutional, Funding: Merck, Janssen, Sanofi, Novartis, Pfizer, Olema. B. McGregor: Financial Interests, Personal, Advisory Board: Exelixis, BMS, Dendreon, SeaGen, Astellas, Eisai, Merck, Nektar; Financial Interests, Personal, Invited Speaker: EMD Serono, SeaGen; Financial Interests, Institutional, Invited Speaker: Pfizer, Exelixis, Exelixis, Calithera, BMS, SeaGen, Aveo; Non-Financial Interests, Member: ASCO. C.S. He: Financial Interests, Personal, Full or part-time Employment: Eisai. R. Perini: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck. K. Mody: Financial Interests, Personal, Full or part-time Employment: Eisai. J. McKenzie: Financial Interests, Personal, Full or part-time Employment, Full time employee: Eisai Inc. 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, Invited Speaker, unpaidhttps://www.accru.org/main/public/index.xhtml: ACCRU; Financial Interests, Personal, Invited Speaker, 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); 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, Peloton; Financial Interests, Institutional, Invited Speaker: 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, Invited Speaker, 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, 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, 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; 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). All other authors have declared no conflicts of interest.