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RCCSeptember 2026
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Renal Cell Carcinoma — Monthly Compass
Sep 01–30, 2026 • Priority Updates • 3–5 minute read
 
A curated, practice-minded digest of what moved in renal cell carcinoma this month — regulatory signals, clinical development, and the most practice-relevant publications.
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renal cell carcinoma updates
Key Highlights
Key Highlights
  • Practice-Changing Updates
    • On September 24, 2026, the FDA approved belzutifan (Welireg) plus lenvatinib (Lenvima) for adults with advanced renal cell carcinoma with a clear cell component after PD‑1/PD‑L1 therapy, based on LITESPARK‑011 demonstrating a statistically significant progression‑free survival benefit versus cabozantinib.
    • The action creates the first approved HIF‑2α inhibitor–VEGFR‑TKI combination in RCC and adds an immediate post‑immunotherapy option in U.S. care pathways.
  • Important Drug Publication Updates
    • The Oncologist reported that belzutifan + lenvatinib improved health‑related quality of life versus cabozantinib in LITESPARK‑011 and that adjuvant pembrolizumab + belzutifan delivered patient‑reported outcome and disease‑free survival advantages in LITESPARK‑022.
    • A pooled analysis in The Oncologist characterized the safety of the next‑generation HIF‑2 inhibitor casdatifan (ARC‑20), supporting subsequent Phase 3 evaluation.
  • Key Clinical Development Updates
    • Casdatifan is entering the Phase 3 PEAK‑1 trial with cabozantinib in advanced ccRCC, and the Phase 3 LITESPARK‑033 is evaluating belzutifan + zanzalintinib versus cabozantinib for recurrence during or after adjuvant anti–PD‑(L)1 therapy.
    • Radiotheranostics progressed with the Phase 3 LUTEON study of 177Lu‑girentuximab in advanced/relapsed ccRCC and first‑in‑human CAIX‑targeted imaging using [111In] XYIMSR‑01 to enable patient selection and dosimetry.
  • Important Clinical Trial Publications
    • The Phase 2 LASER trial demonstrated antitumor activity of 177Lu‑PSMA‑617 in PSMA‑positive metastatic clear cell RCC, supporting exploration of PSMA‑directed radioligand therapy in RCC.
    • KCRS publications described differential recurrence patterns with adjuvant pembrolizumab versus observation, informing surveillance and salvage strategy design post‑nephrectomy.
  • Key Conference Updates
    • KCRS 2026 (abstracts published September 2, 2026) highlighted RCC’s expansion beyond VEGF/IO into radiotheranostics, HIF‑2–anchored combinations across perioperative and salvage settings, and engineered cellular therapies with localized checkpoint delivery.
  • Emerging Themes & Macro-Trends
    • Post‑checkpoint second‑line therapy is shifting toward HIF‑2/VEGFR‑TKI combinations, with payer adoption influenced by management of HIF‑2–related anemia/hypoxia and VEGFR‑TKI toxicities.
    • Radiotheranostics are poised to secure niches in PSMA‑ or CAIX‑selected ccRCC while adjuvant IO + HIF‑2 combinations could challenge pembrolizumab monotherapy pending mature overall survival results.
FDA Approvals/Withdrawals
FDA Approvals/Withdrawals
  • There are no press releases between 2026-09-01 and 2026-09-30 about renal cell carcinoma.
Clinical Development Regulatory Updates
Clinical Development Regulatory Updates
  • FDA approved Merck’s HIF-2α inhibitor belzutifan (Welireg) in combination with Eisai’s lenvatinib (Lenvima) on September 24, 2026 for adults with advanced renal cell carcinoma with a clear cell component after PD-1/PD-L1 inhibitor therapy, based on LITESPARK-011. The agency noted use of the Assessment Aid during review, reflecting a completed U.S. regulatory action for this RCC regimen. ¹ (read more)
  • Merck announced U.S. FDA approval of Welireg (belzutifan) plus Lenvima (lenvatinib) for certain previously treated adults with advanced ccRCC, highlighting that this is the first approved combination of a HIF-2α inhibitor and a VEGFR-TKI. The approval was supported by LITESPARK-011, which showed a statistically significant PFS benefit vs cabozantinib. ² (read more)
  • Eisai issued a companion press release with Merck confirming FDA approval of Lenvima plus Welireg for previously treated advanced ccRCC. The companies emphasized the regulatory milestone and positioned the combo as a new U.S. treatment option following PD‑1/PD‑L1 therapy. ³ (read more)
  • The ASCO Post reported FDA’s approval of belzutifan plus lenvatinib for adults with advanced ccRCC after prior PD‑1/PD‑L1 therapy. The coverage summarized the registrational LITESPARK‑011 results that underpinned the U.S. regulatory decision. ⁴ (read more)
  • Urology Times covered the FDA approval of belzutifan plus lenvatinib for advanced clear cell RCC and outlined the key efficacy endpoints from LITESPARK‑011. The article underscores the regulatory clearance for the post‑immunotherapy setting. ⁵ (read more)
  • Memorial Sloan Kettering Cancer Center published a news item on September 28, 2026 noting the FDA’s September 24 approval of belzutifan plus lenvatinib for clear cell kidney cancer. The piece credits MSK leadership in the pivotal study supporting this regulatory outcome. ⁶ (read more)
  • FDA’s “What’s New Related to Drugs” page for September 30, 2026 listed the approval of belzutifan in combination with lenvatinib for advanced RCC with a clear cell component. This entry reflects the agency’s end‑of‑month regulatory communication capturing the RCC decision. ⁷ (read more)
Conference
Major Conference Updates
Conference Information
  • 2026 Kidney Cancer Research Summit (KCRS), InterContinental Boston, Boston, MA, USA; July 23–24, 2026 (hybrid). Abstracts published September 2, 2026 in The Oncologist, Vol. 31, Supplement 3. (read more)
  • Overall sentiment: RCC research is broadening beyond VEGF/IO into radiotheranostics, HIF‑2–anchored combinations, and engineered immunity, with biomarker work maturing to guide perioperative and salvage decisions. (read more)
  • Theme 1: Radiotheranostics Expand into RCC
    • Significance: Theranostics is moving from prostate into molecularly selected ccRCC, opening new options for patients progressing after IO/TKIs. (read more)
    • Mechanism insights / clinical impact: PSMA-directed 177Lu‑PSMA‑617 showed antitumor activity in PSMA‑positive ccRCC (LASER), while CAIX platforms are advancing with a Phase 3 trial of 177Lu‑girentuximab (LUTEON; NCT07197580) and first‑in‑human imaging with [111In] XYIMSR‑01 to enable patient selection and dosimetry—positioning RCC for true radiotheranostic care pathways. (read more)
    • Patient populations affected: PSMA‑positive metastatic ccRCC; CAIX‑high advanced/relapsed ccRCC suitable for 177Lu‑girentuximab or CAIX‑guided protocols. (read more)
  • Theme 2: HIF‑2–Centered Combinations Across the Continuum
    • Significance: Rapid regulatory momentum plus broader pipelines signal a HIF‑2 backbone in second line and potentially earlier settings. FDA approved belzutifan (Welireg) + lenvatinib (Lenvima) on September 24, 2026. (read more)
    • Mechanism insights / clinical impact: Belzutifan combinations improve PFS vs cabozantinib (LITESPARK‑011) and show favorable PROs; adjuvant pembrolizumab + belzutifan demonstrates PRO and DFS advantages (LITESPARK‑022), and post‑adjuvant recurrence is being addressed (LITESPARK‑033). Next‑gen HIF‑2 inhibitor casdatifan showed pooled safety (ARC‑20) and is entering Phase 3 with cabozantinib (PEAK‑1). (read more)
    • Patient populations affected: Adults with advanced ccRCC after PD‑(L)1 therapy; high‑risk post‑nephrectomy candidates; patients relapsing after adjuvant IO. (read more)
  • Theme 3: Engineered Cellular Immunity and In‑situ Checkpoint Delivery
    • Significance: Novel designs aim to overcome antigen heterogeneity and TME immunosuppression while minimizing on‑target/off‑tumor risk. (read more)
    • Mechanism insights / clinical impact: LNK001 uses an AND‑logic CAIX/ENPP3 CAR to sharpen tumor selectivity; anti‑CAIX/CD70 DFIR CAR‑T secretes anti‑PD‑1/CTLA‑4 bispecific payload for local checkpoint blockade; mRNA vaccine targets are expanding via HERV‑derived antigens—collectively pointing to combination‑ready, precision immunotherapy. (read more)
    • Patient populations affected: Heavily pretreated metastatic ccRCC in early‑phase trials; biomarker‑defined subsets (CAIX/ENPP3, CD70). (read more)
  • Theme 4: Biomarkers and Perioperative Integration
    • Significance: Translational biomarkers and surgical‑IO strategies are refining who benefits from adjuvant therapy and cytoreduction. (read more)
    • Mechanism insights / clinical impact: Plasma KIM‑1 associated with DFS (TransRAMPART; aRCC); baseline TCR diversity linked to first‑line ICI response; recurrence patterns differ with adjuvant pembrolizumab vs observation; consolidative nephrectomy outcomes and Cyto‑KIK data support selective surgery with IO/TKIs. (read more)
    • Patient populations affected: High‑risk localized RCC post‑nephrectomy; metastatic patients on ICI considering cytoreductive or consolidative surgery. (read more)
  • Significance
    • Expected clinical or translational readouts: Phase 3 LUTEON (177Lu‑girentuximab), PEAK‑1 (casdatifan + cabozantinib), and LITESPARK‑033 (belzutifan + zanzalintinib) will set next benchmarks; first‑in‑human CAR‑T programs (e.g., ATHENA for LNK001) are poised for initial safety signals. (read more)
    • Regulatory or policy implications: Immediate uptake of belzutifan + lenvatinib into post‑PD‑(L)1 algorithms; toxicity management (anemia/hypoxia; TKI AEs) will drive payer adoption. (read more)
    • Potential shifts in standard of care: Post‑checkpoint second‑line may favor HIF‑2/TKI combos; radiotheranostics could establish niches in PSMA‑ or CAIX‑selected ccRCC; adjuvant IO + HIF‑2 may challenge pembrolizumab monotherapy pending mature OS. (read more)
    • Strategic implications: Invest in CAIX/PSMA diagnostics to enable theranostics; co‑develop HIF‑2 combinations across lines; build cell‑therapy manufacturing/logistics; integrate KIM‑1/TCR diversity into trial enrichment. (read more)
Publications Related to Approved Drugs
Unknown Drug
There are no new publication updates during the 2026-09-01 to 2026-09-30 for renal cell carcinoma.
New Publications Related to Drugs in Clinical Trial Development
Phase 3
Model-based clinical pharmacology profiling of subcutaneous nivolumab in renal cell carcinoma: Bridging to alternative dosing regimens and indications. A model-informed drug development (MIDD) approach successfully established pharmacokinetic (PK) noninferiority for a subcutaneous (SC) nivolumab regimen (1200 mg every 4 weeks) compared to the intravenous (IV) formulation in renal cell carcinoma. This simulation-based framework demonstrated comparable benefit-risk profiles, supporting the use of nivolumab SC across existing adult solid tumor indications and leading to its FDA approval. ()
Clinical Trials
Clinical Trials Summary
Number of Clinical Trials in renal cell carcinoma updated from 2026-09-01 to 2026-09-30:
Phase 1Phase 1/2Phase 2Phase 2/3Phase 3Phase 4Total
Enrolling by Invitation-------
Not Yet Recruiting2-4--17
Recruiting81215-3-38
Available-------
Approved for Marketing-------
Active, Not Recruiting1148-2-25
Completed222---6
Total231829-5176
Phase 1 Clinical Trials within 3 Months of Primary Completion Date:
DRUGNCTIDStatusClinical Trial NameCompletion Date
AI-061 NCT05858736 COMPLETED Safety, Pharmacokinetics (PK) and Efficacy of AI-061, A 1:1 Co-formulation of AI-025 (Anti-PD-1) and ONC-392 (Anti-CTLA-4) Antibodies in Advanced Solid Tumors: An Open-Label Phase 1 Study 2026-07-31
Indocyanine Green NCT04084067 COMPLETED Indocyanine Green (ICG) Guided Tumor Resection 2026-08-26
Cabozantinib S-malate, : Ipilimumab, : Nivolumab NCT02496208 ACTIVE_NOT_RECRUITING A Phase 1 Study of Cabozantinib Plus Nivolumab (CaboNivo) Alone or in Combination With Ipilimumab (CaboNivoIpi) in Patients With Advanced/Metastatic Urothelial Carcinoma and Other Genitourinary Tumors 2026-09-30
Belzutifan NCT02974738 ACTIVE_NOT_RECRUITING A Phase 1, Dose-Escalation and Expansion Trial of PT2977, a HIF-2α Inhibitor, in Patients With Advanced Solid Tumors 2026-10-08
Enfortumab Vedotin, Erdafitinib NCT04963153 ACTIVE_NOT_RECRUITING Phase Ib Trial of Erdafitinib Combined With Enfortumab Vedotin Following Prior Therapies for Metastatic Urothelial Carcinoma With FGFR2/3 Genetic Alterations 2026-12-01
Phase 2 Clinical Trials within 3 Months of Primary Completion Date:
DRUGNCTIDStatusClinical Trial NameCompletion Date
Belzutifan NCT04489771 COMPLETED Phase 2 Study of MK-6482 in Participants With Advanced Renal Cell Carcinoma 2026-08-25
Folic Acid NCT03581773 COMPLETED FASTERCC: Folic Acid Supplement Versus Placebo for Treating Mucositis Adverse Events in Metastatic Renal Cell Carcinoma Patients Receiving Targeted Therapy. A Randomized, Double-blind Trial From the Danish Renal Cancer Group (DARENCA Study-4) 2026-09-22
INCB099280 NCT05879822 ACTIVE_NOT_RECRUITING A Phase 2 Study Evaluating INCB099280 in Participants With Select Solid Tumors Who Are Immune Checkpoint Inhibitor Naive 2026-09-30
Neoadjuvant Pembrolizumab, Neoadjuvant Lenvatinib, Adjuvant Pembrolizumab NCT05319015 RECRUITING A Phase II Study of the Safety and Efficacy of Neoadjuvant Lenvatinib and Pembrolizumab in Patients With Renal Cell Carcinoma and IVC Tumor Thrombus 2026-12
Phase 3 Clinical Trials within 3 Months of Primary Completion Date:
DRUGNCTIDStatusClinical Trial NameCompletion Date
Avelumab NCT03815643 ACTIVE_NOT_RECRUITING An Open-Label, Multicenter Follow-up Study to Collect Long-term Data on Participants From Multiple Avelumab (MSB0010718C) Clinical Studies 2026-11-24
Phase 4 Clinical Trials within 3 Months of Primary Completion Date:
No phase 4 trials completing within the next three months.
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