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RCCJanuary 2026
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Renal Cell Carcinoma — Monthly Compass
Jan 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 5.6 years of follow-up, the final CheckMate 9ER analysis confirmed that first-line nivolumab plus cabozantinib delivers superior overall survival, progression-free survival, and objective response rates versus sunitinib without new safety signals in advanced RCC.
    • A partitioned survival analysis of CheckMate 9ER demonstrated that the overall survival benefit of nivolumab plus cabozantinib is chiefly driven by longer time on protocol therapy and extended treatment-free survival compared with sunitinib.
  • Key Clinical Development Updates
    • Telix conducted an FDA Type A meeting in January 2026 for Zircaix (TLX250‑Px) to resolve clinical comparability between ZIRCON-trial and scaled-up commercial product, reported alignment on key resubmission elements pending minutes, and continues its Expanded Access Program.
  • Important Clinical Trial Publications
    • In the randomized Phase 2 TACITO trial, fecal microbiota transplantation from complete responders added to pembrolizumab plus axitinib extended median progression-free survival to 24.0 months versus 9.0 months in treatment‑naïve metastatic RCC, validating microbiome augmentation to potentiate first‑line ICI‑TKI therapy.
    • The Phase 1 PERFORM study showed that healthy-donor fecal microbiota transplantation with immune checkpoint inhibitors was safe and yielded a 50% objective response rate in metastatic RCC, with engraftment of anti-inflammatory taxa correlating with reduced toxicity and improved efficacy.
  • Key Conference Updates
    • At JPM 2026, sponsors positioned casdatifan (HIF‑2α) for TKI‑sparing first‑line regimens with planned Phase 3 initiation and February 2026 ARC‑20 monotherapy updates, including combinations with PD‑1 and the anti‑PD‑1/CTLA‑4 bispecific volrustomig.
    • VEGF/MET TKIs remained the access and clinical backbone with cabozantinib leading RCC TKI use and serving as comparator/partner in pivotal studies such as LITESPARK‑033 (zanzalintinib plus belzutifan versus cabozantinib), while non‑clear cell efforts (e.g., STELLAR‑304) target mid‑2026 toplines.
  • Emerging Themes & Macro-Trends
    • Model‑informed systems pharmacology (QCIC) is enabling biomarker‑guided dose‑schedule optimization for IO/anti‑VEGF combinations in advanced RCC by integrating pharmacokinetics with immunobiology to derive a Tumor Response Index and candidate response biomarkers.
    • Advancement of HIF‑2α–based TKI‑sparing regimens toward Phase 3 in 2026 may prompt payer reassessment of TKI‑anchored step‑therapy norms, elevating differentiation via safety and biomarker‑guided optimization as strategic imperatives.
FDA Approvals/Withdrawals
FDA Approvals/Withdrawals
  • There are no press releases between 2026-01-01 and 2026-01-31 about renal cell carcinoma.
Clinical Development Regulatory Updates
Clinical Development Regulatory Updates
  • Telix Pharmaceuticals reported in a January 20, 2026 corporate update that it held an additional FDA Type A meeting that month for Zircaix (TLX250‑Px, 89Zr‑DFO‑girentuximab), its PET imaging candidate for clear cell renal cell carcinoma (ccRCC), to address clinical comparability between ZIRCON trial material and scaled‑up commercial product. Telix stated it believes it has alignment with FDA on key resubmission aspects and will provide a further update upon receipt of meeting minutes; the TLX250‑Px Expanded Access Program remains active.¹ (telixpharma.com) (read more)
Publications Related to Approved Drugs
Phase 3
cabozantinib
Final analysis of nivolumab plus cabozantinib for advanced renal cell carcinoma from the randomized phase III CheckMate 9ER trial. With a median follow-up of 5.6 years, this final analysis confirms the sustained long-term efficacy of nivolumab plus cabozantinib, demonstrating superior progression-free survival, overall survival, and objective response rates compared to sunitinib in previously untreated advanced renal cell carcinoma. The safety profile remained consistent with prior reports without new safety signals, reinforcing this combination regimen as a robust standard of care for first-line treatment.
Phase 3
cabozantinib
Partitioned overall survival: comprehensive analysis of survival states over 4 years in CheckMate 9ER comparing first-line nivolumab plus cabozantinib versus sunitinib in advanced renal cell carcinoma. This partitioned survival analysis indicates that the overall survival advantage of first-line nivolumab plus cabozantinib is primarily driven by extended time on protocol therapy and longer treatment-free survival compared to sunitinib. While the sunitinib arm showed more survival time occurring after the initiation of second-line therapy, the combination arm offered a distinct benefit in maintaining patients in earlier, treatment-controlled states.
New Publications Related to Drugs in Clinical Trial Development
Early Phase 1
Genomic and Molecular Associations with Preoperative Immune Checkpoint Inhibition in Patients with Stage III Clear Cell Renal Cell Carcinoma. Preoperative immune checkpoint inhibition (ICI) in stage III ccRCC favorably altered the tumor microenvironment to resemble treatment-naïve non-recurrence profiles, though it did not directly improve survival in this small cohort. A validated four-gene signature (GZMK, GZMA, ITGAL, IL7R) was identified as modifiable by ICI and associated with improved overall survival, highlighting a potential biomarker strategy for patient selection.
Phase 1
Fecal microbiota transplantation plus immunotherapy in metastatic renal cell carcinoma: the phase 1 PERFORM trial. This Phase 1 trial demonstrates that healthy donor fecal microbiota transplantation (FMT) combined with immune checkpoint inhibitors is safe and achieved a 50% objective response rate in metastatic RCC. Successful engraftment of anti-inflammatory taxa correlated with reduced toxicity and improved efficacy, whereas specific dysbiosis markers like Segatella copri were linked to severe immune-related adverse events.
N/A
Geriatric prehabilitation prior to surgery for kidney tumors: Study protocol for Pre-KiT - A randomized controlled trial. The Pre-KiT trial protocol outlines a randomized study evaluating whether a one-month multimodal geriatric prehabilitation program can improve postoperative recovery in frail elderly patients with localized RCC. This low-resource intervention aims to establish feasibility and effectiveness in enhancing quality of recovery and long-term survival outcomes in a vulnerable surgical population.
Phase 1/Phase 2
Fecal microbiota transplantation plus pembrolizumab and axitinib in metastatic renal cell carcinoma: the randomized phase 2 TACITO trial. In the Phase 2 TACITO trial, fecal microbiota transplantation from complete responders significantly extended median progression-free survival (24.0 vs 9.0 months) in treatment-naïve metastatic RCC patients receiving pembrolizumab plus axitinib. The findings confirm that donor microbiome engraftment enhances clinical outcomes, supporting FMT as a viable strategy to potentiate first-line ICI-based therapies.
Phase 2
The Effect of Taking Cabozantinib with a Light Breakfast: A Randomized Crossover Pharmacokinetic Study (SKIPPY 1). This pharmacokinetic study reveals that administering cabozantinib with a light breakfast results in only a marginal increase in drug exposure compared to the fasted state, without increasing serious adverse events. These findings support a more patient-centric dosing strategy, allowing patients who struggle with fasting requirements to safely take the medication with food.
Conference
Major Conference Updates
Conference Information
  • 44th Annual J.P. Morgan Healthcare Conference (JPM 2026); San Francisco, CA; January 12–15, 2026. (read more)
  • Overall sentiment: RCC momentum centers on HIF-2α backbones and durable VEGF/MET TKI anchoring, with companies signaling imminent 2026 readouts and Phase 3 initiations that could reshape first-line strategy. (read more)
  • Theme 1: HIF-2α Backbones Aim for TKI‑Sparing Frontlines
    • Significance: Sponsors are positioning “casdatifan (AB521)” to become a foundational ccRCC therapy, explicitly targeting a first-line Phase 3 and a paradigm shift that delays TKIs (toxicity advantage, sequencing flexibility). (read more)
    • Mechanism insights / clinical impact: HIF‑2α inhibition (casdatifan) shows low primary progression in early studies; combinations span PD‑1 (zimberelimab) and anti‑PD‑1/CTLA‑4 bispecific “volrustomig” (eVOLVE‑RCC02). Updated late‑line monotherapy data from “ARC‑20” are slated for a February 2026 medical meeting; “PEAK‑1” (casdatifan + cabozantinib) targets IO‑experienced ccRCC. (read more)
    • Patient populations affected: IO‑experienced metastatic ccRCC (PEAK‑1); first‑line ccRCC in planned TKI‑free regimens (casdatifan + zimberelimab/volrustomig). (read more)
  • Theme 2: VEGF/MET TKIs Remain the Clinical and Access Anchor
    • Significance: “CABOMETYX (cabozantinib)” retains the leading TKI share in RCC and is the most‑prescribed TKI in IO combinations—sustaining reimbursement familiarity and ensuring backbone availability for trials and practice. (read more)
    • Mechanism insights / clinical impact: TKIs (VEGFR/MET blockade) continue to serve as control/comparator and combination partners in pivotal RCC trials, including Merck‑sponsored “LITESPARK‑033” evaluating zanzalintinib + WELIREG (belzutifan) versus cabozantinib. (read more)
    • Patient populations affected: Broad RCC use (mono‑ and IO‑TKI); first‑line advanced RCC post‑adjuvant IO and non‑clear cell RCC programs (e.g., “STELLAR‑304” topline expected mid‑2026). (read more)
  • Theme 3: Model‑Informed Optimization of IO/Anti‑VEGF Regimens
    • Significance: Quantitative cancer‑immunity cycle (QCIC) modeling proposes biomarker‑guided, dose‑schedule optimization for bevacizumab + atezolizumab in advanced RCC—supporting precision dosing to widen therapeutic index. (read more)
    • Mechanism insights / clinical impact: Systems pharmacology integrates PK with immunobiology to define a Tumor Response Index and identify candidate biomarkers for response, potentially informing future RCC combination designs. (read more)
    • Patient populations affected: Advanced RCC cohorts where IO/anti‑VEGF strategies are standard; applicability to virtual “biomarker‑selected” subsets guiding prospective trial stratification. (read more)
  • Significance
    • Expected clinical or translational readouts: ARC‑20 updated monotherapy data (February 2026), plus mid‑2026 readouts from RCC pivotal programs (e.g., STELLAR‑304), will calibrate first‑line choices and combo backbones. (read more)
    • Regulatory or policy implications: If HIF‑2α TKI‑sparing regimens advance to Phase 3 in 2026, payers may reassess step‑therapy norms anchored on TKIs. (read more)
    • Potential shifts in standard of care: Success of casdatifan‑based regimens could move HIF‑2α inhibition earlier, reducing upfront TKI toxicity; conversely, durable TKI leadership sustains IO‑TKI as default. (read more)
    • Strategic implications: Prioritize HIF‑2α combination portfolios (PD‑1, bispecifics) and maintain TKI access leverage; anticipate fast‑follower competition and differentiation via safety (TKI‑sparing) and biomarker‑guided optimization. (read more)
Clinical Trials
Clinical Trials Summary
Number of Clinical Trials in renal cell carcinoma updated from 2026-01-01 to 2026-01-31:
Phase 1Phase 1/2Phase 2Phase 2/3Phase 3Phase 4Total
Enrolling by Invitation-------
Not Yet Recruiting212-1-6
Recruiting15811-3-37
Available-------
Approved for Marketing-------
Active, Not Recruiting6510-4-25
Completed2-1---3
Total251424-8-71
Phase 1 Clinical Trials within 3 Months of Primary Completion Date:
DRUGNCTIDStatusClinical Trial NameCompletion Date
: Pembrolizumab, : MK-4700 NCT06894771 COMPLETED A Phase 1 Open-label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MK-4700 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced or Metastatic Solid Tumors 2025-11-24
[68Ga]Ga-OncoCAIX NCT06840548 COMPLETED A Phase I Study to Evaluate the Safety and Dosimetry of 68Ga-OncoCAIX in Patients With CAIX-positive Cancer 2025-11-28
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
Cadonilimab Combined With Lenvatinib NCT06138496 COMPLETED Phase II Single-arm Clinical Study of the Efficacy and Safety of Cadonilimab in Combination With Lenvatinib Neoadjuvant Therapy for Patients With High-risk Renal Carcinoma Indicating Partial Nephrectomy 2025-12-31
Cabozantinib NCT04022343 ACTIVE_NOT_RECRUITING A Phase 2 Study of Neoadjuvant Cabozantinib in Patients With Locally Advanced Non-Metastatic Clear Cell Renal Cell Carcinoma 2026-03-01
Phase 3 Clinical Trials within 3 Months of Primary Completion Date:
DRUGNCTIDStatusClinical Trial NameCompletion Date
Lenvatinib, Everolimus, Sunitinib, Pembrolizumab NCT02811861 ACTIVE_NOT_RECRUITING A Multicenter, Open-label, Randomized, Phase 3 Trial to Compare the Efficacy and Safety of Lenvatinib in Combination With Everolimus or Pembrolizumab Versus Sunitinib Alone in First-Line Treatment of Subjects With Advanced Renal Cell Carcinoma (CLEAR) 2026-03-31
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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