Advanced or metastatic clear cell RCC select phase 3 clinical trials in the first- and second-line settings

Authored by Toni Choueiri, published on 2026-02-23 00:59:54.0

Selected phase 3 clinical trials in progress in the first- and second-line settings for advanced or metastatic clear cell RCC patients. (A) Design of the MK-6482-012 trial (NCT04736706) in the first-line setting, looking at pembrolizumab/lenvatinib in two triplet combinations with either a quavonlimab co-formulation or belzutifan versus standard of care. (B) Design of the Alliance-A031704/PDIGREE trial (NCT03793166) in the first-line setting, looking at a risk-adapted approach after induction treatment withnivolumab/ipilimumab. (C) Design of the LITESPARK-011 trial (NCT04586231) in the second- and third-line settings or after neoadjuvant or adjuvanttreatment, including a combination of belzutifan/lenvatinib in comparison to cabozantinib as monotherapy. IMDC = International Metastatic RCC Database Consortium; KPS = Karnofsky performance score; R = randomization; RCC = renal cell carcinoma; CR = complete response; PD = progressive disease.First and Second-line Treatments in Metastatic Renal Cell Carcinoma, European Urology, Volume 87, Issue 2, 2025, Pages 143-154, https://doi.org/10.1016/j.eururo.2024.10.019.

  1. (A) Histologically confirmed clear cell RCC
    Advanced or metastatic No prior systemic treatment KPS score ≥ 70%
    • R 1:1:1 (N=1432)
      • Pembrolizumab + Lenvatinib
      • Belzutifan + Pembrolizumab + Lenvatinib
      • Quavonlimab/ Pembrolizumab + Lenvatinib
  2. (B) Histologically confirmed metastatic clear cell RCC
    No prior systemic therapy (adjuvant sunitinib allowed) IMDC intermediate or poor risk
    • Nivolumab + Ipilimumab
      • Nivolumab
      • Cabozantinib
      • R 1:1 (N=696)
        • Nivolumab
        • Nivolumab + Cabozantinib
  3. (C) Histologically/ cytologically confirmed advanced or metastatic clear cell RCC
    Disease progression after first or second line after PD(L)1 therapy or as (neo)adjuvant treatment with progression on or within 6 months of last dose Received ≤ 2 lines of therapy KPS score ≥ 70%
    • R 1:1 (N=708)
      • Belzutifan + Lenvatinib
      • Cabozantinib
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