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194 RCC Clinical Trials Recruiting Now (August 2026): Renal Cell Carcinoma — Belzutifan LITESPARK-034, HIF-2α, Casdatifan, IO+TKI, Zanzalintinib, CAR-T

Last updated: August 14, 2026

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Current Clinical Trial Landscape

Active research areas in 2026:

Already approved: Nivolumab + cabozantinib, pembrolizumab + lenvatinib (Lenvima, CLEAR Phase 3), nivolumab + ipilimumab, axitinib + pembrolizumab (1L advanced); pembrolizumab adjuvant (KEYNOTE-564, intermediate-high/high risk after nephrectomy); belzutifan (VHL-associated tumors, and advanced ccRCC post anti-PD-1 and VEGF-TKI). Lenvima + everolimus is also FDA-approved 2L RCC after prior VEGF-targeted therapy (Study 205 Phase 2).

Post-ASCO 2026 update (June 13): The HIF-2α + next-generation TKI combination is the dominant Phase 3 storyline in advanced clear-cell RCC. Belzutifan + zanzalintinib has two recruiting Phase 3 trials: LITESPARK-034 (NCT07489495) in RCC broadly, and NCT07227402 in patients recurring after adjuvant therapy. Casdatifan + cabozantinib (NCT07011719) provides a competing HIF-2α / TKI Phase 3 comparator. Patients should ask whether they meet HIF-2α combination eligibility — particularly in the post-IO+TKI second-line setting where standard options remain limited.

Recruiting Trials by Treatment Stage

🧬 Belzutifan (HIF-2α) & the LITESPARK Program in RCC — Recruiting Trials

Belzutifan (Welireg, MK-6482) is the first-in-class HIF-2α inhibitor, FDA-approved for advanced clear-cell RCC (2023, after anti-PD-1 and VEGF-TKI) and VHL-associated tumors. Merck's LITESPARK trial program is testing belzutifan across nearly every RCC setting. The headline 2026 study is LITESPARK-034 — belzutifan + zanzalintinib (a next-generation VEGFR/MET/AXL TKI) — the registrational Phase 3 that could establish the first HIF-2α + TKI doublet in advanced ccRCC. Below is the full recruiting belzutifan/LITESPARK list, more complete than a manual ClinicalTrials.gov or WHO ICTRP search returns:

Competing HIF-2α inhibitor: NCT07011719 tests casdatifan + cabozantinib vs placebo + cabozantinib in advanced ccRCC (Phase 3) — the head-to-head benchmark for the HIF-2α + TKI approach against belzutifan's LITESPARK-034. If you have advanced clear-cell RCC and have progressed on IO + VEGF-TKI, ask your oncologist whether you qualify for a HIF-2α combination trial, or match your profile in minutes.

First-Line (Treatment-Naive Advanced/Metastatic)

IO+TKI and IO+IO combinations are standard first-line. Trials explore HIF-2α addition, novel triplets, IO de-escalation, and adjunctive biotherapy:

  • Adjunctive / microbiome modulation:

    • After IO Progression (Second-Line+)

    A major unmet need — what to do after IO+TKI failure:

    Neoadjuvant / Perioperative

    Adjuvant (After Surgery)

    Oligometastatic / Radiation Approaches

    Novel Approaches

    Frequently Asked Questions

    How do I find kidney cancer clinical trials?

    Paste your medical summary into ClinTrialFinder to get AI-matched renal cell carcinoma trials in minutes. The tool considers your histology (clear cell, papillary, chromophobe, sarcomatoid features), IMDC risk group, prior therapies (IO, TKI, belzutifan), and VHL status to find the most relevant trials.

    What renal cell carcinoma trials are currently recruiting?

    There are 194 recruiting interventional trials for RCC in August 2026, of which 17 are Phase 3. They include immunotherapy combinations (IO+TKI, IO+IO, triplets), TKI-based regimens (cabozantinib, lenvatinib, axitinib, tivozanib, zanzalintinib), HIF-2α inhibitors (belzutifan, casdatifan), CAR-T cell therapy (CD70-targeted), radiopharmaceuticals (177Lu-TLX250), and adjuvant programs following the KEYNOTE-564 pembrolizumab adjuvant standard.

    What is LITESPARK-034 and is it recruiting?

    LITESPARK-034 (also called LS-034 or MK-6482-034, NCT07489495) is a recruiting Phase 3 trial of belzutifan (Welireg, the first-in-class HIF-2α inhibitor) + zanzalintinib (a next-generation VEGFR/MET/AXL TKI) in renal cell carcinoma. It's the registrational study that could establish the first HIF-2α + TKI doublet in advanced clear-cell RCC. It belongs to Merck's broader LITESPARK belzutifan program, which also includes the LITESPARK-043 extension (NCT07405164) and a belzutifan + zanzalintinib trial for recurrent kidney cancer after adjuvant therapy (NCT07227402). There are 9 recruiting belzutifan RCC trials in August 2026 — see the Belzutifan & LITESPARK Program section above for the full list spanning first-line, post-IO, localized, and cell-therapy combinations.

    What are the new Phase 3 belzutifan combinations in RCC in 2026?

    Belzutifan (the first-in-class HIF-2α inhibitor, FDA-approved for advanced RCC in 2023) now has two parallel Phase 3 programs in combination with zanzalintinib, a next-generation VEGFR/MET/AXL TKI: LITESPARK-034 (NCT07489495) in RCC, and a recurrent-after-adjuvant trial (NCT07227402). Casdatifan (a competing HIF-2α inhibitor) is in Phase 3 combined with cabozantinib (NCT07011719). The HIF-2α + next-gen TKI combination is the major Phase 3 storyline in advanced ccRCC for 2026.

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    This page is for information only and is not medical advice. ClinTrialFinder helps you find clinical trials that may match your situation, but enrollment decisions and treatment choices should always be made with your oncologist or healthcare team. Trial eligibility, recruitment status, and treatment details can change — verify directly with the trial sponsor or on ClinicalTrials.gov before acting on any information here.