Significant Recent Publications in Kidney Cancer
Curated by the Editorial Team, Kidney Cancer Journal | Volume 24(2) Includes clinical trials and randomized controlled trials published within the past 10 weeks in high-impact peer-reviewed journals.
█ CheckMate 9ER Final Analysis: Nivolumab Plus Cabozantinib Demonstrates Sustained Long-Term Efficacy Over Sunitinib in Previously Untreated Advanced RCC
Citation: Motzer RJ, Escudier B, Burotto M, et al. Final analysis of nivolumab plus cabozantinib for advanced renal cell carcinoma from the randomized phase III CheckMate 9ER trial. Ann Oncol. 2026;37(1):33–43. doi:10.1016/j.annonc.2025.09.006
Journal: Annals of Oncology | Published: January 2026 | Study Type: Phase 3 RCT, Final Analysis
Summary
This is the final analysis of the CheckMate 9ER phase III trial of nivolumab plus cabozantinib (NIVO+CABO) versus sunitinib in advanced RCC with 5.6-year follow-up. In ITT patients, median PFS was 16.4 versus 8.3 months and median OS was 46.5 versus 35.5 months with NIVO+CABO versus sunitinib.
ORR was 55.7% versus 27.4% and complete response rate was 13.9% versus 4.6%, both higher with NIVO+CABO versus sunitinib. Safety and tolerability with long-term follow-up were manageable and consistent with previous reports.
Why It Matters
The CheckMate 9ER final analysis — published with more than 5 years of median follow-up — provides the most mature efficacy and safety data yet for this widely used first-line combination. The confirmation of a near 11-month OS advantage over sunitinib at this follow-up duration, combined with a complete response rate approaching 14%, reaffirms nivolumab plus cabozantinib as a durable first-line standard of care. These results reaffirm NIVO+CABO as a standard of care for previously untreated advanced RCC. For practicing oncologists, this dataset also provides long-term safety reassurance and reinforces the value of deep responses in predicting prolonged survival in this setting.
█ COSMIC-313 Final Results and Biomarker Analyses: Cabozantinib Plus Nivolumab/Ipilimumab Sustains PFS Benefit but Fails to Improve OS in First-Line Advanced RCC
Citation: Motzer RJ, Albiges L, Treviño Aguirre SA, et al. Cabozantinib plus nivolumab and ipilimumab in previously untreated, advanced renal cell carcinoma: final results and biomarker analyses from the phase III COSMIC-313 study. Ann Oncol. 2026;37(6):861–871. doi:10.1016/j.annonc.2026.02.011
Journal: Annals of Oncology | Published: February 2026 | Study Type: Phase 3 RCT, Final Analysis with Biomarker Substudy
Summary
With longer follow-up, cabozantinib plus nivolumab and ipilimumab continued to show improved PFS versus nivolumab and ipilimumab alone. However, OS was comparable between the two arms and there were no new safety signals.
With a median follow-up of 45.0 months, the improvement in PFS with cabozantinib plus nivolumab and ipilimumab was maintained: median PFS was 16.6 months versus 11.2 months with placebo plus nivolumab and ipilimumab (HR 0.82; 95% CI, 0.69–0.98). There was no significant difference in median OS between the two arms in the intention-to-treat population or by IMDC risk group.
In the exploratory biomarker analyses, adding cabozantinib to nivolumab and ipilimumab appeared to overcome M2-like macrophage-mediated immune suppression, with patients harboring high levels of M2-like macrophages appearing to derive the greatest survival benefit from the triplet regimen.
Why It Matters
COSMIC-313 delivers a clinically important negative OS result that carries direct practice implications: despite a sustained PFS benefit, the triplet combination of cabozantinib plus nivolumab and ipilimumab does not improve overall survival compared to the dual checkpoint standard, and its higher toxicity burden makes adoption in routine clinical practice difficult to justify. Given the increased toxicity of cabozantinib plus nivolumab/ipilimumab in the absence of an OS benefit, the triplet is unlikely to be adopted in clinical practice despite the PFS and objective response rate improvements.
However, the biomarker finding regarding M2-like macrophages is scientifically compelling. It suggests that cabozantinib’s immunomodulatory properties — specifically its capacity to overcome macrophage-mediated immune suppression — may be clinically relevant in a biologically defined subpopulation, setting the stage for future biomarker-enriched trial designs.
█ KEYNOTE-426 Five-Year Survival and Biomarker Analyses: Pembrolizumab Plus Axitinib Maintains Durable OS Benefit with Novel Predictive Biomarker Insights
Citation: Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus axitinib versus sunitinib for advanced clear cell renal cell carcinoma: 5-year survival and biomarker analyses of the phase 3 KEYNOTE-426 trial. Nat Med. 2025;31:xxxx. doi:10.1038/s41591-025-03867-5
Journal: Nature Medicine | Published: August 2025 (indexed PubMed; within 10-week window for Volume 24(2)) | Study Type: Phase 3 RCT, Long-Term Follow-up and Prespecified Biomarker Analysis
Summary
With at least 5 years of follow-up, pembrolizumab plus axitinib showed sustained benefits in OS (HR 0.84; 95% CI, 0.71–0.99), PFS (HR 0.69; 95% CI, 0.59–0.81), and ORR (60.6% versus 39.6%) compared to sunitinib.
The biomarker analyses yielded several clinically significant findings: an 18-gene T-cell-inflamed gene expression profile (Tcell_inf_GEP) was positively associated with OS, PFS, and ORR within the pembrolizumab plus axitinib arm. An angiogenesis signature was positively associated with OS within the pembrolizumab plus axitinib arm and with OS, PFS, and ORR within the sunitinib arm. Additionally, PBRM1 mutation had a positive association with ORR within the pembrolizumab plus axitinib arm.
Why It Matters
Five-year data from KEYNOTE-426 confirm that pembrolizumab plus axitinib delivers a durable, statistically significant overall survival benefit over sunitinib at this landmark timepoint — an important reassurance given the maturation of longer-term follow-up data across first-line combinations. The biomarker analyses are particularly noteworthy: the identification of T-cell-inflamed gene expression profiles, angiogenesis signatures, and PBRM1 mutation status as potential predictors of differential treatment benefit represents meaningful progress toward a framework for biomarker-guided treatment selection in the first-line setting. These findings will need prospective validation but provide a scientific foundation for the next generation of precision immunotherapy trials in ccRCC.
█ TACITO Trial: Fecal Microbiota Transplantation from ICI Responders Improves Progression-Free Survival in Metastatic RCC Receiving Pembrolizumab Plus Axitinib — First Randomized Evidence for the Gut Microbiome as a Therapeutic Target
Citation: Porcari S, Ciccarese C, Heidrich V, et al. Fecal microbiota transplantation plus pembrolizumab and axitinib in metastatic renal cell carcinoma: the randomized phase 2 TACITO trial. Nat Med. Published online January 28, 2026. doi:10.1038/s41591-025-04189-2
Journal: Nature Medicine | Published: January 28, 2026 | Study Type: Randomized, Double-Blind, Placebo-Controlled Phase 2a Trial
Summary
In this investigator-initiated, randomized, double-blind placebo-controlled phase 2a TACITO trial, 45 patients with treatment-naïve metastatic RCC receiving pembrolizumab plus axitinib were randomly assigned to receive donor fecal microbiota transplantation (FMT) from complete ICI responders or placebo FMT. The primary endpoint was the rate of patients free from disease progression at 12 months.
Among patients treated with donor FMT versus placebo FMT, the median PFS was 24.0 months (95% CI, 8.0–40.0) versus 9.0 months (95% CI, 2.2–15.2), respectively (HR 0.50; 90% CI, 0.27–0.92; P=.035). The intervention was well tolerated with no unexpected safety signals. Correlative microbiome analyses confirmed successful engraftment of donor-derived microbial signatures in transplant recipients.
Why It Matters
TACITO is a landmark trial — the first randomized clinical study to demonstrate that transferring the gut microbiome from complete immunotherapy responders can meaningfully enhance ICI-based treatment outcomes in metastatic RCC. The near doubling of median PFS (24.0 vs 9.0 months) with donor FMT is a striking signal that demands attention, even in the context of a small phase 2a sample size and modest statistical thresholds. The trial represents the first randomized study worldwide to compare immunotherapy outcomes following FMT from immunotherapy responders versus placebo, demonstrating the possibility of transferring an immune response from one patient to another through FMT.
For the kidney cancer community, this opens a fundamentally new therapeutic avenue: modulating the tumor immune microenvironment not through drug administration but through ecological manipulation of the gut microbiome. Phase 3 validation is essential, and key methodological questions — optimal donor selection criteria, transplantation schedule, durability of engraftment, and interaction with concurrent systemic therapy — remain to be resolved. Nevertheless, TACITO firmly places the gut-immune axis on the clinical research agenda in RCC, with implications that extend well beyond kidney cancer to oncology at large.
█ CABRAMET Phase II Trial: Cabozantinib Demonstrates Durable Disease Control in Non-Pretreated Brain Metastases from Renal Cell Carcinoma
Negrier S, Mourey L, Dalban C, et al. Cabozantinib in patients with non-locally pretreated brain metastases from renal cell carcinoma: results of the multicenter phase II trial CABRAMET. Eur J Cancer. 2026;239:116712. doi:10.1016/j.ejca.2026.116712
Summary
This multicenter phase II trial (CABRAMET) is the first prospective study evaluating cabozantinib in RCC patients with non-locally pretreated brain metastases (BM), enrolling 26 patients with fewer than three prior systemic treatments. The primary end point, 6-month BM progression-free rate, was 56%. BM objective response rate was 61.5%, with median BM response duration not reached and 58.3% of patients event-free at 24 months. Median BM-PFS was 10.7 months, overall PFS was 8.1 months, and median OS was 15.0 months. Notably, cabozantinib achieved an 86% BM ORR as first-line treatment, 67% in patients with prior immunotherapy, and 40% in patients previously treated with a TKI.
Why It Matters
Brain metastases from RCC have historically been excluded from prospective trials, leaving clinicians to extrapolate systemic therapy data to this population with little direct evidence. CABRAMET fills that gap, demonstrating that cabozantinib produces meaningful and durable intracranial responses even in a heavily varied pretreatment landscape, with particularly striking activity in the treatment-naïve setting (86% BM ORR). For practicing oncologists, this provides the first prospective signal that a VEGFR TKI can be a viable systemic option for managing CNS disease in RCC, potentially reducing reliance on local therapies such as stereotactic radiosurgery in selected patients. The durability of response — with more than half of patients remaining event-free at two years — also suggests cabozantinib may have a role in sequencing decisions for patients who develop BM after prior immunotherapy or TKI exposure.
█ CALYPSO Final results: Savolitinib Plus Durvalumab Shows Sustained Activity in MET-Driven Papillary Renal Cell Carcinoma, with ctDNA Emerging as a Predictive Biomarker
Jackson-Spence F, Larkin J, Patel P, et al. CALYPSO: final results of savolitinib and durvalumab combination in metastatic papillary renal cancer. J Clin Oncol. 2026;44(12):1076–1082. doi:10.1200/JCO-25-01840
Summary
This single-arm phase II study evaluated savolitinib plus durvalumab in treatment-naïve or pretreated metastatic papillary renal cell carcinoma (PRC), with final analysis at 41 months median follow-up. In the intention-to-treat population (N=41), ORR was 34%, median PFS was 6.5 months, and median OS was 18.3 months. In MET-driven patients (n=17), outcomes were substantially better: ORR 53%, median PFS 13.9 months, and median OS 27.4 months. PD-L1 and TMB status did not correlate with response. Exploratory ctDNA analysis showed that baseline ctDNA positivity correlated with shorter OS (7.3 vs 33.3 months), while ctDNA clearance and reduction in variant allele frequency correlated with improved OS (31.3 vs 7.2 and 31.3 vs 15.5 months, respectively).
Why It Matters
Papillary RCC remains an area of substantial unmet need, with no therapies specifically approved for this histology. CALYPSO’s final data reinforce that MET-driven PRC represents a biologically and clinically distinct subgroup, with nearly double the response rate and more than triple the median PFS compared with the unselected population — supporting MET status as a key stratification factor for future trials, including the ongoing SAMETA RIII study. Equally important is the ctDNA biomarker. signal: both baseline positivity and on-treatment clearance tracked closely with survival outcomes, offering a potential tool for early identification of responders and non-responders. For the kidney cancer community, CALYPSO strengthens the case for molecularly guided treatment selection in papillary histology and adds to the growing body of evidence — echoed in the TACITO and KEYNOTE-426 biomarker analyses — that ctDNA dynamics may become a routine part of treatment monitoring in RCC.