29: LITESPARK-011: Belzutifan Plus Lenvatinib Versus Cabozantinib: A Randomized, Open-Label Phase 3 Study in Patients With Advanced Renal Cell Carcinoma (RCC) After Anti–PD-1/PD-L1 Therapy
Memorial Sloan Kettering Cancer Center New York, New York, United States of America
Background Anti–PD-1/PD-L1–based therapies are standard of care for advanced RCC; however, there is an unmet need for treatment options following disease progression. Hypoxia-inducible factor (HIF)-2α is a key oncogenic driver in clear cell RCC (ccRCC). Promising antitumor activity has been observed with the first-in-class HIF-2α inhibitor belzutifan (MK-6482) as monotherapy (phase 1) and combined with cabozantinib in heavily pretreated ccRCC (phase 2). This randomized, open-label, active-controlled phase 3 trial, LITESPARK-011 (NCT04586231), will evaluate efficacy and safety of belzutifan + lenvatinib versus cabozantinib in patients with advanced ccRCC that progressed after anti–PD-1/PD-L1 therapy.
Methods Eligible patients will have locally advanced (LA) or metastatic ccRCC, disease progression on or after first- or second-line anti–PD-1/PD-L1 monotherapy or combination therapy (most recent treatment), or as adjuvant treatment with progression on or within 6 months of last dose, ≤2 prior systemic regimens (≤1 anti–PD-1/PD-L1 for adjuvant or LA/metastatic RCC), measurable disease (RECIST v1.1), and KPS ≥70%. Adults ≥18 years will be randomly assigned (1:1) to receive oral belzutifan 120 mg QD + lenvatinib 20 mg QD or oral cabozantinib 60 mg QD. Patients will be stratified by International mRCC Database Consortium prognostic scores (0, 1 or 2, or 3–6), prior therapies (1 or 2), and geographic region (North America, Western Europe, or rest of the world). Treatment will continue until disease progression, unacceptable toxicity, or consent withdrawal. Primary endpoints are progression-free survival per RECIST v1.1 by blinded independent central review [BICR] and overall survival. Secondary objectives are objective response rate and duration of response per RECIST v1.1 by BICR and safety and tolerability. Planned enrollment is ~708 patients. Recruitment is underway in 17 countries.