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RCCMarch 2026
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Renal Cell Carcinoma — Monthly Compass
Mar 01–31, 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
  • Important Drug Publication Updates
    • With 9.3-year median follow-up, the phase III CheckMate 214 final analysis confirmed sustained overall survival and durable responses for first-line nivolumab plus ipilimumab over sunitinib with fewer severe treatment-related adverse events, reinforcing its foundational standard-of-care status in advanced renal cell carcinoma.
    • A two-stage estimation in the phase 3 CheckMate 9ER trial adjusting for subsequent therapies demonstrated a stronger overall survival advantage for cabozantinib plus nivolumab versus sunitinib (adjusted HR 0.53 vs unadjusted HR 0.79), reinforcing the robust clinical efficacy of the combination in advanced renal cell carcinoma.
  • Key Clinical Development Updates
    • On March 2, 2026, FDA granted Priority Review to supplemental applications for adjuvant belzutifan (WELIREG) plus pembrolizumab (KEYTRUDA) or pembrolizumab and berahyaluronidase alfa-pmph (KEYTRUDA QLEX) for clear cell RCC at increased risk of recurrence following nephrectomy, assigning a June 19, 2026 PDUFA date based on LITESPARK-022 results.
    • FDA accepted sNDAs for belzutifan plus lenvatinib (LENVIMA) in previously treated advanced clear cell RCC after prior PD‑1/PD‑L1 therapy with an October 4, 2026 PDUFA date, supported by phase 3 LITESPARK‑011 versus cabozantinib.
  • Important Clinical Trial Publications
    • CALYPSO reported overall survival benefit for savolitinib plus durvalumab in MET-driven metastatic papillary renal cancer, with baseline ctDNA positivity correlating with shorter overall survival and ctDNA clearance correlating with improved overall survival.
    • The GRANT (GRade, Age, Nodes, Tumor) score was prospectively validated in the EA8143 PROSPER trial as prognostic for relapse-free and overall survival, particularly in nonclear cell renal cell carcinoma, supporting its clinical use for postoperative risk stratification.
  • Key Conference Updates
    • At EAU26, LITESPARK‑022 showed adjuvant pembrolizumab plus belzutifan improved disease‑free survival versus pembrolizumab plus placebo (HR 0.72; 24‑month DFS 80.7% vs 73.7%), including in sarcomatoid features, with manageable safety characterized by anemia, ALT increase, and hypoxia (grade ≥3 AEs 52.1% vs 30.2%).
    • CAIX‑targeted PET/CT altered hypothetical management in 48.6% of indeterminate renal mass cases in ZIRCON‑X, corroborated by real‑world high specificity and excellent tolerability, while first‑in‑human [68Ga]Ga‑OncoCAIX demonstrated favorable biodistribution and biologic selectivity.
  • Emerging Themes & Macro-Trends
    • Momentum is building toward biology‑driven intensification in early RCC and rapid maturation of CAIX‑targeted PET as a decision‑informing tool, while the pipeline broadens beyond ICI/TKIs into HIF‑2α next‑generation inhibitors, CAR‑T constructs, and ferroptosis targeting.
    • Anticipated readouts and strategic implications include LITESPARK‑022 overall survival maturation and expanded CAIX‑PET prospective utility, with prioritization of HIF‑2α combinations across settings, investment in CAIX‑theranostics platforms, and partnership development around DFIR CAR‑T and ferroptosis approaches for non‑ccRCC niches.
FDA Approvals/Withdrawals
FDA Approvals/Withdrawals
  • There are no press releases between 2026-03-01 and 2026-03-31 about renal cell carcinoma.
Clinical Development Regulatory Updates
Clinical Development Regulatory Updates
  • Merck reported that FDA granted Priority Review to supplemental applications for belzutifan (WELIREG) plus pembrolizumab (KEYTRUDA) or pembrolizumab and berahyaluronidase alfa-pmph (KEYTRUDA QLEX) as adjuvant therapy for adults with clear cell RCC at increased risk of recurrence following nephrectomy. The agency set a PDUFA target action date of June 19, 2026, based on LITESPARK-022 results. ¹ (read more)
  • Urology Times reported FDA acceptance of sNDAs from Merck and Eisai for belzutifan (WELIREG) plus lenvatinib (LENVIMA) in previously treated advanced clear cell RCC after prior PD‑1/PD‑L1 therapy. The filing carries a PDUFA target action date of October 4, 2026, supported by phase 3 LITESPARK‑011 data versus cabozantinib. ² (read more)
  • BioPharm International highlighted Merck’s phase 3 LITESPARK‑022 adjuvant data in clear cell RCC and noted FDA’s Priority Review of supplemental submissions for the belzutifan plus pembrolizumab regimens. The article confirmed a June 19, 2026 PDUFA date for the adjuvant applications. ³ (read more)
  • OncLive emphasized that Priority Review filings for Merck’s belzutifan plus pembrolizumab (and KEYTRUDA QLEX) in adjuvant RCC signal imminent practice‑shaping regulatory decisions. The piece references FDA acceptance of a belzutifan sNDA and KEYTRUDA QLEX sBLAs with a June 19, 2026 PDUFA date. ⁴ (read more)
  • The ASCO Post reviewed LITESPARK‑022 and stated that on March 2, 2026 FDA granted Priority Review to two supplemental applications for adjuvant belzutifan combinations in clear cell RCC. The report also cites the June 19, 2026 PDUFA target date. ⁵ (read more)
Conference
Major Conference Updates
Conference Information
  • EAU26 (41st Annual EAU Congress), London, UK; March 13–16, 2026. AACR Special Conference in Cancer Research: Advances in Kidney Cancer Research, W Philadelphia, Philadelphia, PA; March 13–16, 2026.
  • Overall sentiment: Momentum toward biology-driven intensification in early RCC and rapid maturation of CAIX-targeted PET as a decision-informing tool; pipeline breadth expands beyond ICI/TKIs into HIF-2α next-gen agents, CAR‑T, and ferroptosis targeting. (read more)
  • Theme 1: Adjuvant HIF‑2α + PD‑1 Intensification
    • Significance: Clear signal that combining HIF‑2α inhibition with PD‑1 blockade is redefining adjuvant strategy for high‑risk ccRCC post‑nephrectomy. (read more)
    • Mechanism insights / clinical impact: LITESPARK‑022 showed pembrolizumab + belzutifan improved disease‑free survival vs pembrolizumab + placebo (HR 0.72; 24‑mo DFS 80.7% vs 73.7%); benefit extended to sarcomatoid features with manageable safety (Grade ≥3 AEs 52.1% vs 30.2%; anemia, ALT increase, hypoxia). (read more)
    • Patient populations affected: ccRCC, M0 intermediate‑high/high risk or M1 NED after surgery; global adjuvant-setting candidates seeking recurrence‑risk reduction. (read more)
  • Theme 2: CAIX‑Targeted PET Driving Precision Triage
    • Significance: CAIX imaging is directly altering clinical decisions for indeterminate renal masses—supporting surveillance in low‑risk cases and directing intervention where ccRCC biology is evident. (read more)
    • Mechanism insights / clinical impact: [89Zr]Zr‑girentuximab PET/CT changed hypothetical management in 48.6% of cases in ZIRCON‑X, with major plan shifts (e.g., biopsy↔surgery); early real‑world series confirmed high specificity for ccRCC and excellent tolerability. First‑in‑human [⁶⁸Ga]Ga‑OncoCAIX demonstrated favorable biodistribution and biologic selectivity, reinforcing theranostic potential. (read more)
    • Patient populations affected: Adults with indeterminate renal masses or suspected ccRCC (primary or recurrent), especially where non‑invasive characterization can avoid unnecessary biopsy/surgery; centers with PET access. (read more)
  • Theme 3: Next‑Gen Biology‑Driven Modalities (HIF‑2α, CAR‑T, Ferroptosis)
    • Significance: Early‑phase and translational sessions highlight diversification beyond checkpoint/TKI toward novel targets and modalities that may reshape later‑line options and rare RCC care. (read more)
    • Mechanism insights / clinical impact: Evidence presented on casdatifan (novel HIF‑2α inhibitor) biology in ccRCC; DFIR CAR‑T design for advanced RCC; ferroptosis as a therapeutic vulnerability in chromophobe RCC—collectively pointing to metabolically and immunologically tuned interventions. (read more)
    • Patient populations affected: Advanced ccRCC after ICI/TKIs, translocation RCC, chromophobe RCC—biomarker‑enriched cohorts likely first to benefit. (read more)
  • Significance
    • Expected clinical or translational readouts: Additional OS maturation from LITESPARK‑022; expanded CAIX‑PET prospective utility; progression of DFIR CAR‑T and HIF‑2α agents (e.g., casdatifan) into patient‑segmented trials. (read more)
    • Regulatory or policy implications: If DFS benefit converts to OS and safety remains acceptable, adjuvant pembrolizumab + belzutifan could prompt guideline updates; CAIX‑PET data support payer discussions around reducing invasive procedures. (read more)
    • Potential shifts in standard of care: Movement from single‑agent adjuvant pembrolizumab toward combination (anti‑PD‑1 + HIF‑2α) in high‑risk post‑op ccRCC; incorporation of CAIX‑PET into diagnostic pathways for indeterminate masses. (read more)
    • Strategic implications: Prioritize HIF‑2α combinations across settings; invest in CAIX‑theranostics platforms; seed partnerships around CAR‑T logistics and ferroptosis tools for non‑ccRCC niches. (read more)
Publications Related to Approved Drugs
Phase 3
['ipilimumab']
Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: final analysis of efficacy and safety from the phase III CheckMate 214 trial. With an unprecedented 9.3-year median follow-up, first-line nivolumab plus ipilimumab demonstrated a sustained, long-term overall survival benefit and durable response rates compared to sunitinib, alongside a lower incidence of severe treatment-related adverse events. These definitive findings solidify the combination as a foundational standard of care for advanced renal cell carcinoma. ()
Phase 3
['cabozantinib']
Two-Stage Estimation of Overall Survival in the Phase 3 CheckMate 9ER Trial, Adjusting for the Impact of Subsequent Therapy. A post hoc analysis adjusting for the confounding effects of subsequent systemic therapies revealed a substantially stronger overall survival benefit for first-line cabozantinib plus nivolumab over sunitinib (adjusted HR 0.53 versus unadjusted HR 0.79). This adjusted survival estimation reinforces the robust clinical efficacy of the cabozantinib and nivolumab combination in advanced renal cell carcinoma. ()
Phase 3
['avelumab', 'axitinib']
Cardiac Biomarkers in Patients With Renal Cell Carcinoma Treated With Immune Checkpoint Inhibitors. Analysis of the JAVELIN Renal 101 trial indicates that a significant proportion of patients with advanced renal cell carcinoma present with elevated cardiac biomarkers at baseline, though treatment-emergent elevations were not directly associated with major adverse cardiac events. This highlights the strategic necessity of establishing baseline biomarker levels prior to initiating immune checkpoint inhibitor therapy to accurately monitor cardiovascular safety. ()
New Publications Related to Drugs in Clinical Trial Development
N/A
CD70-Targeted Immuno-PET/CT for Detecting Heterogeneous CD70 Expression in Lymphomas: A Pilot Clinical Study. CD70-targeted immuno-PET/CT effectively visualizes CD70 expression in patients with lymphoma, potentially serving as a valuable tool for improving CD70-targeted therapies. The tracer uptake correlated well with CD70 expression and showed noninferior diagnostic performance compared with [18F]FDG across all evaluated categories. ()
Phase 3
A prospective external validation of the GRade, Age, Nodes and Tumor score in the ECOG-ACRIN EA8143 PROSPER trial. The GRade, Age, Nodes and Tumor (GRANT) score was prospectively validated in the PROSPER study, demonstrating prognostic value for both relapse-free survival and overall survival, especially in nonclear cell renal cell carcinoma. This further supports its use in clinical practice to refine recurrence risk stratification in patients with surgically treated renal cell carcinoma. ()
Phase 3
CALYPSO: Final Results of Savolitinib and Durvalumab Combination in Metastatic Papillary Renal Cancer. Savolitinib plus durvalumab shows overall survival benefit in MET-driven papillary renal cancer, supporting the ongoing SAMETA RIII trial. Circulating tumor DNA (ctDNA) may be a useful predictive biomarker, as baseline ctDNA positivity correlated with shorter overall survival, while ctDNA clearance correlated with improved overall survival. ()
N/A
Geriatric prehabilitation prior to surgery for kidney tumors: Study protocol for Pre-KiT - A randomized controlled trial. The Pre-KiT trial explores if a pragmatic geriatric prehabilitation strategy, including home-based exercise, geriatric assessment, and smoking cessation support, is effective and feasible for older frail patients with localized renal cell carcinoma. If successful, this low-resource approach could improve standard care and postoperative outcomes, including recovery and quality of life. ()
Phase 4
Model-Informed Precision Dosing of Protein Kinase Inhibitors: Evaluation of Model-Averaging and Flattened Priors Methods. A comprehensive fit-for-purpose validation of model-informed precision dosing (MIPD) for sunitinib and pazopanib demonstrated that model averaging was robust across different scenarios and should be preferred to using a single model. The benefit of the model-averaging method for the MIPD of sunitinib and pazopanib is likely applicable to other protein kinase inhibitors. ()
Phase 2
The Effect of Taking Cabozantinib with a Light Breakfast: A Randomized Crossover Pharmacokinetic Study (SKIPPY 1). Taking cabozantinib with a light breakfast leads to a small increase in exposure without an increased risk for exposure-related toxicity. Patients for whom taking cabozantinib in a fasted state is unpleasant are now able to take it with a light breakfast. ()
Phase 2
CaboPoint: A Phase 2 Study of Second-line Cabozantinib After Checkpoint Inhibitor-based Combination Therapy in Patients with Metastatic Renal Cell Carcinoma. The CaboPoint study demonstrated that second-line cabozantinib after first-line checkpoint inhibitor-based combinations is effective and safe for patients with advanced renal cell carcinoma. This study provides a benchmark for future second-line advanced renal cell carcinoma studies. ()
Clinical Trials
Clinical Trials Summary
Number of Clinical Trials in renal cell carcinoma updated from 2026-03-01 to 2026-03-31:
Phase 1Phase 1/2Phase 2Phase 2/3Phase 3Phase 4Total
Enrolling by Invitation1-1---2
Not Yet Recruiting3-4-1-8
Recruiting9161014-40
Available-------
Approved for Marketing-------
Active, Not Recruiting625-4-17
Completed--1-1-2
Total191821110-69
Phase 1 Clinical Trials within 3 Months of Primary Completion Date:
DRUGNCTIDStatusClinical Trial NameCompletion Date
Oxaliplatin, AB598, Zimberelimab, Leucovorin, Fluorouracil NCT05891171 ACTIVE_NOT_RECRUITING A Phase 1/1b Study to Evaluate the Safety and Tolerability of AB598 Monotherapy and Combination Therapy in Participants With Advanced Malignancies 2026-03
Phase 2 Clinical Trials within 3 Months of Primary Completion Date:
DRUGNCTIDStatusClinical Trial NameCompletion Date
Cabozantinib NCT03945773 COMPLETED A Phase II, Multicentre, Open-label Study of Cabozantinib as 2nd Line Treatment in Subjects With Unresectable, Locally Advanced or Metastatic Renal Cell Carcinoma With a Clear-Cell Component Who Progressed After 1st Line Treatment With Checkpoint Inhibitors. 2026-02-12
Entrectinib NCT02568267 ACTIVE_NOT_RECRUITING An Open-Label, Multicenter, Global Phase 2 Basket Study of Entrectinib for the Treatment of Patients With Locally Advanced or Metastatic Solid Tumors That Harbor NTRK1/2/3, ROS1, or ALK Gene Rearrangements 2026-05-14
Phase 3 Clinical Trials within 3 Months of Primary Completion Date:
DRUGNCTIDStatusClinical Trial NameCompletion Date
: Pembrolizumab NCT03142334 COMPLETED A Phase 3, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Pembrolizumab (MK-3475) as Monotherapy in the Adjuvant Treatment of Renal Cell Carcinoma Post Nephrectomy (KEYNOTE-564) 2026-02-04
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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