LBA2 - Belzutifan versus everolimus for previously treated advanced clear cell renal cell carcinoma (ccRCC): Updated follow-up of the East Asian subgroup of the randomized phase III LITESPARK-005 trial

Background

In the randomized phase 3 LITESPARK-005 study (NCT04195750), belzutifan improved progression-free survival (PFS) and objective response rate (ORR) vs everolimus in a global population of patients (pts) with advanced ccRCC whose disease progressed on or after anti–PD-(L)1 and VEGF-TKI therapy. We present updated data with a >2-year minimum follow-up of East Asian pts from LITESPARK-005.

Methods

Adults enrolled at sites in Hong Kong, Japan, South Korea, or Taiwan with advanced ccRCC who received 1-3 prior systemic regimens were randomly assigned 1:1 to oral belzutifan 120 mg or everolimus 10 mg once daily. Primary end points were PFS per RECIST v1.1 by blinded independent central review (BICR) and overall survival (OS). The key secondary end point was ORR per RECIST v1.1 by BICR. Other secondary end points included duration of response (DOR) and safety.

Results

A total of 78 pts were enrolled (n = 39 in each arm). As of the April 15, 2024 data cutoff date, median follow-up was 33.4 mo (range, 26.9-44.2). As of the data cutoff date, 30% of pts were ongoing treatment with belzutifan vs 3% with everolimus. Median PFS was 7.5 mo with belzutifan vs 5.7 mo with everolimus (HR, 0.54; 95% CI, 0.30-0.98); 24-mo PFS rates were 30% vs 4%. Median OS was 29.7 mo with belzutifan vs 30.8 mo with everolimus (HR, 0.76; 95% CI, 0.39-1.46); 24-mo OS rates were 59% vs 56%. ORR was consistent with previous reports (31% vs 0%). Median DOR was not reached (range, 12.9-39.8+) for belzutifan. One pt (3%) discontinued belzutifan and 7 (18%) discontinued everolimus due to all-cause adverse events (AEs). Grade 3-5 treatment-related AEs occurred in 53% of pts with belzutifan and 33% of pts with everolimus. One death (3%) occurred in the belzutifan arm due to treatment-related AEs (multiple organ dysfunction syndrome).

Conclusions

With a >2-year minimum follow-up of East Asian pts from LITESPARK-005, PFS and ORR continued to favor belzutifan over everolimus. Safety was consistent with prior reports and with the global population. Results support belzutifan as a potential treatment option for East Asian pts with advanced RCC after both anti–PD-(L)1 and VEGF-TKI therapy.

Clinical trial identification

NCT04195750.

Editorial acknowledgement

Medical writing and/or editorial assistance was provided by Mallory Campbell, PhD, and Robert Steger, PhD, of ApotheCom (Yardley, PA, 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

J. Lee: Financial Interests, Personal, Stocks or ownership: Johnson & Johnson/Janssen, Amgen, Merck, Innovent Biologics, Black Diamond Therapeutics, Karyopharm Therapeutics, Zymeworks; Financial Interests, Personal, Advisory Role: Merck, AstraZeneca, Astellas Korea, Novartis, Amgen, Daiichi Sankyo/AstraZeneca; Financial Interests, Institutional, Research Funding: Pfizer, Janssen, Novartis, Bristol Myers Squibb, Roche/Genentech, AstraZeneca/MedImmune, MSD, Bayer Schering Pharma, Seagen, GI Innovation, Amgen, Oscotec, Arcus Biosciences, Eutilex, LG Chem, Merck KGaA, Loxo/Lilly; Financial Interests, Personal, Speaker, Consultant, Advisor: Bristol Myers Squibb, AstraZeneca, MSD Korea. S.H. Park: Financial Interests, Personal, Other, Payment or Honoraria: Ono Pharma; Financial Interests, Personal, Advisory Board, Payment or Honoraria: Pfizer, Astellas. T. Kato: Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Speaker’s Bureau: Merck. N. Masumori: Financial Interests, Personal, Invited Speaker: Merck, Takeda, Ono; Financial Interests, Institutional, Research Funding: MSD. H. Fujimoto: Financial Interests, Personal and Institutional, Principal Investigator: MSD, Roche, AstraZeneca. M. Eto: Financial Interests, Personal, Other, Honoraria: Takeda Pharmaceutical, Janssen Pharmaceuticals, Astellas Pharma; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal and Institutional, Funding: Astellas Pharma, Sanofi, Takeda Pharmaceuticals. T. Kishida: Non-Financial Interests, Personal and Institutional, Principal Investigator: MSD, AstraZeneca. Y. Su: Financial Interests, Personal, Speaker’s Bureau: Merck, Amgen, Merck Serono, Astellas; Financial Interests, Personal, Advisory Board: Merck, Merck Serono; Financial Interests, Personal, Principal Investigator: Merck, Astellas. Y. Miura: Financial Interests, Personal, Invited Speaker: Takeda, MSD, Bristol Myers Squibb, Ono Pharmaceutical, Eisai, Merck Biopharma, Taiho Pharmaceutical, Janssen, Astellas Pharma; Financial Interests, Institutional, Local PI: Ono Pharmaceutical, MSD, Janssen, Daiichi Sankyo, Takeda, Taiho Pharmaceutical, Novartis. N. Matsubara: Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Institutional, Coordinating PI: Janssen, Roche, MSD, Taiho, Pfizer, Chugai; Financial Interests, Institutional, Local PI: AstraZeneca, Bayer, Astellas, Amgen, Eisai, Eli Lilly, AbbVie. H. Kitamura: Financial Interests, Personal, Invited Speaker: Astellas, AstraZeneca, MSD, Sanofi, Bristol Myers Squibb, Merck Biopharma, Takeda, Janssen; Financial Interests, Personal, Advisory Board: Kissei; Financial Interests, Institutional, Trial Chair: AstraZeneca; Financial Interests, Institutional, Local PI: MSD, Bristol Myers Squibb. A. Xing, R. Perini, D. Vickery: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck. B.I. Rini: Financial Interests, Personal, Advisory Board: Merck, BMS, AVEO, Pfizer, Eisai, EUSA, Debiopharm, Genentech/Roche; Financial Interests, Personal, Other, Partnership on podcasts and meeting: MashupMD; Financial Interests, Institutional, Coordinating PI: Merck, Surface Oncology, Daiichi Sankyo, Adela; Financial Interests, Institutional, Other, Research funding to institution: BMS; Financial Interests, Institutional, Steering Committee Member: Pfizer; Financial Interests, Institutional, Local PI: Astra-Zeneca; Financial Interests, Institutional, Funding: AVEO; Financial Interests, Institutional, Other, Study funding: Janssen. All other authors have declared no conflicts of interest.