LBA74 - Final analysis of the phase III LITESPARK-005 study of belzutifan versus everolimus in participants (pts) with previously treated advanced clear cell renal cell carcinoma (ccRCC)

Background

Belzutifan significantly improved progression-free survival (PFS) and objective response rate (ORR) vs everolimus in pts with advanced ccRCC after immune checkpoint and antiangiogenic agents in LITESPARK-005 (NCT04195750).

Methods

Eligible pts were adults with advanced ccRCC and 1–3 prior systemic regimens including ≥1 PD-(L)1 inhibitor and ≥1 VEGFR-TKI. Pts were randomized 1:1 to belzutifan 120 mg or everolimus 10 mg QD until progression or unacceptable AEs. PFS per RECIST 1.1 by central review and overall survival (OS) were the dual primary endpoints. ORR per RECIST 1.1 by central review was a key secondary endpoint. Duration of response (DOR) and safety were secondary endpoints. No formal statistical testing was performed at final analysis (FA) for PFS and ORR as these endpoints were positive at first interim analysis.

Results

746 pts were allocated to belzutifan (n=374) or everolimus (n=372). At FA (data cutoff: April 15, 2024), median follow-up was 35.8 mo (range 26.9–49.2); 14.5% of pts had ongoing treatment with belzutifan vs 1.4% with everolimus. PFS benefit was maintained with belzutifan vs everolimus (median 5.6 mo vs 5.6 mo; HR 0.75; 95% CI 0.63–0.88); estimated PFS rate at 12 mo (33.7% vs 17.6%) and at 24 mo (17.5% vs 4.1%) favored belzutifan. Median OS was 21.4 mo with belzutifan vs 18.2 mo with everolimus (HR 0.92; 95% CI 0.77–1.10; P=0.18). Estimated OS rate was 67.9% vs 65.8% at 12 mo and 45.2% vs 41.2% at 24 mo. ORR was consistent with prior reports (22.7% vs 3.5%). Median (range) DOR was 19.3 mo (1.9+–40.1+) vs 13.7 mo (3.8–29.5+). Fewer pts discontinued belzutifan (6.2%) vs everolimus (15.3%) due to an any-cause AE. Median duration of therapy was longer with belzutifan (7.6 mo vs 3.9 mo). Rate of grade ≥3 TRAEs (39.5% vs 40.0%) was similar between arms.

Conclusions

Belzutifan continued to show PFS and ORR benefits vs everolimus, although significant improvement in OS was not observed. With >2 yrs minimum follow-up, the safety profile of belzutifan was consistent with prior reports. Final analysis results of LITESPARK-005 support belzutifan as a treatment option in advanced ccRCC after PD-(L)1 inhibitor and VEGFR-TKI therapy.

Clinical trial identification

NCT04195750.

Editorial acknowledgement

Editorial assistance was provided by Ina Nikolaeva, PhD, an employee of 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

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: AstraZeneca; Financial Interests, Institutional, Funding: AVeo; Financial Interests, Institutional, Other, Study funding: Janssen. C. Suarez Rodriguez: Financial Interests, Personal, Invited Speaker: Astellas Pharma, Bristol Myers Sqquib (Inst), IPSEN, Hoffmann-La Roche Ltd, Merck; Financial Interests, Personal, Advisory Board: Bristol Myers Sqquib (Inst), Ipsen, Hoffmann-La Roche Ltd, Merck Sharp and Dohme, Eisai; Financial Interests, Institutional, Funding: Ipsen; Financial Interests, Institutional, Research Grant: Pfizer. L. 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