1453P - Phase II study of belzutifan plus cabozantinib for previously treated advanced renal cell carcinoma (RCC): Update from cohort 2 of LITESPARK-003

Background

First-line treatment with immune checkpoint inhibitors (ICIs) is standard of care for advanced RCC. However, most patients will experience disease progression. Belzutifan, a first-in-class HIF-2α inhibitor, has shown durable responses in heavily pretreated RCC. Cabozantinib, a VEGF, AXL, and MET inhibitor, is approved for advanced RCC. The ongoing, open-label, phase 2 LITESPARK-003 study (NCT03634540) investigated belzutifan + cabozantinib in pts with no prior treatment (cohort 1) and pts with prior ICI therapy (cohort 2). Preliminary analysis from cohort 2 showed antitumor activity and acceptable safety. Here, we present updated data with ∼2 years of follow-up from cohort 2.

Methods

Pts with advanced clear cell RCC and had previously received ICI therapy and ≤2 systemic treatment regimens received belzutifan 120 mg QD PO once daily plus cabozantinib 60 mg QD PO. The primary end point was ORR (CR + PR) per RECIST v1.1 by investigator review. Secondary end points were DOR, PFS, OS, and safety.

Results

Of 52 pts enrolled in cohort 2, 42 (81%) discontinued treatment. Most pts had IMDC intermediate/poor risk (n=41; 79%), one prior line of therapy (n=29; 56%), and prior ICI only (n=28; 54%). Median follow-up was 24.6 mo (range, 17.9-39.8). ORR was 31% (1 CR, 15 PRs) and 32 pts (62%) had a best response of SD. Median DOR was 18.6 mo (range, 4.2+ to 22.8); 9 pts remained in response for ≥12 mo. Median PFS was 13.8 mo (95% CI, 9.2-19.4) and median OS was 24.0 mo (95% CI, 20.0-37.4). At 12 mo, PFS rate was 56% and OS rate was 77%. Responses were consistent across subgroups (Table). In all pts, 51 (98%) had a treatment-related AE (TRAE); 34 (65%) had a grade ≥3 TRAE. No pt had a grade 4 TRAE; 1 pt (2%) died due to a TRAE (respiratory failure). Table: 1453P

Conclusions

With 24.6 mo of follow-up, belzutifan plus cabozantinib had manageable safety and continued to show promising antitumor activity in pts with advanced RCC previously treated with ICIs.

Clinical trial identification

NCT03634540, August 16, 2018.

Editorial acknowledgement

Medical writing and/or editorial assistance was provided by Robert Steger, PhD, and Matt Grzywacz, PhD, of ApotheCom (Yardley, PA, USA). 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

D.F. McDermott: Financial Interests, Personal, Advisory Role, n/a: BMS; Pfizer; Merck; Alkermes, Inc.; EMD Serono; Eli Lilly and Company; Iovance; Werewolf Therapeutics; Calithera Biosciences; Synthekine, Inc.; Johnson & Johnson; Financial Interests, Personal, Research Grant, n/a: BMS; Merck; Genentech; Pfizer; Exelixis; X4 Pharma; Alkermes, Inc.; Checkmate Pharmaceuticals; CRISPR Therapeutics. 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). 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