Renal Cell Carcinoma
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May 25 – Jun 01, 2026
Pretreatment intratumoral mature TLSs in non-clear cell renal cell carcinoma are associated with response to immunotherapy rechallenge.
J IMMUNOTHER CANCER · Q1 JOURNAL - RANK #12/183TOP-TIER
This prospective human clinical trial evaluated the efficacy, safety, and predictive markers of immune checkpoint inhibitor (ICI) rechallenge in 39 patients with metastatic non-clear cell renal cell carcinoma (nccRCC). The study reported a median progression-free survival (PFS) of 11.8 months, an objective response rate (ORR) of 13.9%, and a disease control rate (DCR) of 69.4%. Patients with a high mature intratumoral tertiary lymphoid structure (m-iTLS) score had significantly better outcomes (ORR: 50.0% vs 0.0%, PFS: 28.2 vs 5.0 months), and ICI rechallenge was well tolerated with no treatment-related deaths observed. The findings highlight potential biomarkers for predicting ICI rechallenge efficacy and emphasize the therapy’s clinical benefit in this patient population, although additional validation is required.
10.1136/jitc-2025-013526
Safety, pharmacokinetics, pharmacodynamics, and antitumor activity of cergutuzumab amunaleukin: a phase I study in patients with advanced and/or metastatic solid tumors.
ESMO OPEN · Q1 JOURNAL - RANK #36/326
This phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of cergutuzumab amunaleukin (CA) in 60 patients with advanced/metastatic CEA-positive solid tumors. The study comprised two parts: single-dose (0.1-6 mg, n=5) and multiple ascending doses (10-40 mg q2w, n=31; 6-30 mg qw, n=24), establishing an MTD of 30 mg q2w with dose-limiting toxicities including Gr4 hypophosphatemia and thrombocytopenia. Pharmacokinetics showed dose-proportional exposure (6-40 mg), and pharmacodynamics revealed preferential expansion of CD8+ T and NK cells. No objective responses were observed, but 11% (6/53) achieved stable disease (median duration 4.5 months), supporting further combination therapy development.
10.1016/j.esmoop.2026.107697
Pembrolizumab plus high-dose IL-2 in advanced clear cell renal cell carcinoma: six-year survival outcomes and molecular signatures from a phase 2 trial.
NAT COMMUN · Q1 JOURNAL - RANK #10/135TOP-TIER
This single-arm phase 2 trial evaluated a fixed-duration regimen of pembrolizumab plus high-dose IL-2 in 26 treatment-naive patients with advanced clear cell renal cell carcinoma. The primary objectives of safety and response were previously met, with the overall response rate exceeding the 45% threshold. At a median follow-up of 76.4 months, the objective response rate was 73%, including 42% complete responses, median overall survival exceeded 84 months, and median progression-free survival was 19.3 months. The authors conclude that this immunotherapy combination yields durable responses and a prolonged treatment-free interval without high-grade toxicities.
10.1038/s41467-026-73336-1
May 18 – May 25, 2026
Cluster Randomized Trial of Intensive Systolic Blood Pressure Control in Patients With Renal Cell or Thyroid Cancer Receiving VEGFR Tyrosine Kinase Inhibitors: ECOG-ACRIN EAQ191.
HYPERTENSION · Q1 JOURNAL - RANK #7/98
This cluster randomized controlled trial assessed the feasibility and safety of intensive systolic blood pressure (SBP) control (<120 mmHg) versus usual care (<140 mmHg) in patients with renal cell or thyroid cancer initiating VEGFR tyrosine kinase inhibitors. A phase II site-based design used 10 sites (5 per arm) enrolling 61 patients (58 renal cell, 3 thyroid), with centralized BP advisory core guidance, home monitoring, and visits at baseline, 1, 2, 3, and 6 months. Mean SBP differences favored intensive control: -12.2 mmHg (95% CI -18.1 to -7.0) at 1 month, -7.6 (95% CI -15.3 to -0.4) at 3 months, and -6.9 (95% CI -19.3 to 6.0) at 6 months; grade 3 adverse events were numerically higher in usual care for kidney injury, hypotension, and dyspnea. The authors conclude this first randomized trial in active cancer patients demonstrates feasibility, safety, and tolerability of intensive SBP control.
10.1161/HYPERTENSIONAHA.125.26016
Long-term outcomes of stereotactic ablative body radiotherapy for primary kidney cancer (TROG 15.03 FASTRACK II): a multicentre, non-randomised, phase 2 study.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This study is a non-randomized, phase 2 clinical trial that evaluated long-term outcomes of stereotactic ablative body radiotherapy (SABR) in treating primary renal cell carcinoma in non-surgical patients. Conducted across eight hospitals, the trial enrolled 71 patients, with 70 receiving treatment. After a median follow-up of 62 months, local control was 100% with no recurrences, grade 4 events, or treatment-related deaths reported. Seven (10%) patients experienced grade 3 adverse events within 9 months after treatment, and the study concluded that SABR is a safe and effective non-invasive treatment option for medically inoperable patients with renal cell carcinoma.
10.1016/S1470-2045(26)00091-4
Ultra-hypofractionated stereotactic ablative body radiotherapy for primary renal cell carcinoma: 5-year outcomes from a pooled analysis of the FASTRACK trials.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This pooled analysis combined data from two prospective clinical trials (FASTRACK phase 1 and FASTRACK II phase 2) evaluating ultra-hypofractionated stereotactic ablative body radiotherapy (SABR) for medically inoperable or high-surgical-risk primary renal cell carcinoma. 103 treated patients (median age 76.9 years) received either 26 Gy in one fraction for tumors ≤4–5 cm or 42 Gy in three fractions for larger lesions; local control, measured with RECIST v1.1, was the primary endpoint and adverse events were graded with CTCAE. Local control was 100 % at 1 year, 98 % (95 % CI 89-100) at both 3 and 5 years, with only one local failure, while grade ≥3 toxicity occurred in 8 % of patients and no grade 4 events or treatment-related deaths were reported. The authors conclude that SABR achieves durable tumor control with low severe toxicity, warranting randomized comparison with surgery.
10.1016/S1470-2045(26)00170-1
May 11 – May 18, 2026
Metastatic tropism of molecularly defined clear-cell renal cell carcinoma clusters.
J CLIN INVEST · Q1 JOURNAL - RANK #5/195TOP-TIER
This study examines the metastatic tropism of molecular subgroups in clear-cell renal cell carcinoma (ccRCC) using data from the IMmotion150 phase II randomized clinical trial involving 305 treatment-naive patients. Patients were assigned to receive atezolizumab, atezolizumab/bevacizumab, or sunitinib, and over 5,000 metastatic sites were analyzed. Key findings include significant differences in metastatic patterns: angiogenic tumors showed higher pancreatic metastases (21% vs. 6.9%; P = 0.002), while proliferative tumors exhibited more lymph node metastases (5.5 vs. 3.5; P = 0.019). Patients with pancreatic metastases treated with sunitinib had improved overall response odds (OR, 7.13; 95% CI, 1.81-28.07; P = 0.0049) and longer progression-free survival (P = 0.02). These findings suggest that ccRCC molecular clusters influence metastasis patterns and may inform therapeutic decision-making.
10.1172/JCI195288
May 04 – May 11, 2026
HPK1 inhibitor NDI-101150 as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors: Phase 1/2 trial results.
CELL REP MED · Q1 JOURNAL - RANK #15/195TOP-TIER
The study evaluates NDI-101150, a selective HPK1 inhibitor, as monotherapy and in combination with pembrolizumab in a phase 1/2 trial involving patients with advanced solid tumors. The monotherapy maximum tolerated dose (MTD) was 150 mg once daily, while doses up to 100 mg once daily were combinable with pembrolizumab without reaching an MTD. In clear cell renal cell carcinoma, the overall response rate was 13.6% (1 complete, 2 partial responses), with a clinical benefit rate of 27.3% and disease control rate of 54.5%. Pharmacodynamic analyses confirmed biomarker inhibition and immune cell recruitment, supporting further development (NCT05128487).
10.1016/j.xcrm.2026.102789
The Phase Ib IMPACT Trial of Intramuscular Personalized Neoantigen Synthetic Long Peptide Vaccines in Patients with Advanced Melanoma and Renal Cell Carcinoma.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
The Phase Ib IMPACT Trial evaluated the safety and immunogenicity of intramuscular personalized neoantigen synthetic long peptide (SLP) vaccines in 12 patients with advanced melanoma (n=9) or renal cell carcinoma (n=3). Patients received vaccines containing ~20 predicted neoantigen peptides with poly-ICLC, monitored for adverse events and immune responses. The vaccine was well-tolerated, with 53% of peptides per patient inducing immunogenic responses, including CD8⁺ and CD4⁺ T-cell activation, and enhanced CD8⁺ infiltration in tumor biopsies. The study concludes that intramuscular neoantigen SLP vaccination is safe and induces robust mutation-specific T-cell immunity, supporting its potential as a peptide-based cancer vaccine strategy.
10.1158/1078-0432.CCR-25-4271
Apr 27 – May 04, 2026
Metastasis-directed Therapy With or Without Pembrolizumab for Oligometastatic Clear Cell Renal Cell Carcinoma: Pooled Analysis of Two Prospective Single-arm Phase 2 Trials.
EUR UROL · Q1 JOURNAL - RANK #3/133TOP-TIER
This study is a pooled analysis of two prospective single-arm phase 2 trials evaluating metastasis-directed therapy (MDT) with or without pembrolizumab (ICI) for oligometastatic clear cell renal cell carcinoma (ccRCC). The primary objective was to compare RECIST-defined progression-free survival (PFS) between MDT+ICI (NCT02855203, n=30) and MDT alone (NCT03575611, n=120), with a secondary focus on peripheral immune populations. After a median follow-up of 34 months, MDT+ICI showed longer PFS that did not reach statistical significance (HR 0.57, 95% CI 0.32-1.02, p=0.058), with greater benefit seen in patients with prior systemic therapy. The study concludes that adding maintenance ICI to MDT improves clinical outcomes and supports initiation of the ASTROs randomized trial (NCT06004336).
10.1016/j.eururo.2026.03.024
Comprehensive Genomic and Transcriptomic Characterization of Matched Primary and Recurrent Tumors in High-risk Localized Renal Cell Carcinoma.
EUR UROL · Q1 JOURNAL - RANK #3/133TOP-TIER
The study aimed to characterize genomic and transcriptomic differences between primary and recurrent tumors in high-risk localized renal cell carcinoma using data from the IMmotion010 trial, where patients were randomized to adjuvant atezolizumab or placebo. Tumor samples from pre-treatment (n=754) and recurrence (n=80) underwent transcriptomic (n=80) and genomic (n=52) analyses, revealing distinct signatures in primary versus recurrent tumors, including angiogenic and T-effector/proliferative differences. Recurrence sites showed upregulated proliferation and stromal biology signatures, with placebo-treated tumors exhibiting increased B cell and macrophage signatures and atezolizumab-treated tumors showing MHC-I downregulation. The findings suggest a potential rationale for VEGF-inhibition post-checkpoint inhibition, though further clinical validation is needed.
10.1016/j.eururo.2026.03.023
Apr 20 – Apr 27, 2026
Camrelizumab plus apatinib for immune checkpoint inhibitor-naive patients with metastatic clear cell renal cell carcinoma after first-line tyrosine kinase inhibitor treatment failure: a single-arm phase 2 trial.
BMC MED · Q1 JOURNAL - RANK #19/332
This two-center, single-arm phase 2 clinical trial prospectively evaluated camrelizumab (200 mg bi-weekly) combined with apatinib (250 mg daily) in 41 immune checkpoint inhibitor-naïve patients with metastatic clear cell renal cell carcinoma who had progressed after first-line tyrosine-kinase inhibitor therapy. Patients were treated until progression or unacceptable toxicity; the primary endpoint was progression-free survival (PFS) with secondary endpoints including overall survival (OS), objective response rate (ORR) and safety. After a median 19.0-month follow-up, median PFS reached 11.6 months (95% CI 6.2–18.5), OS was not yet reached, and ORR was 41.5 % (95% CI 26.3–57.9). Grade 3–4 treatment-related adverse events included elevated ALT (26.8 %), elevated AST (22.0 %) and proteinuria (22.0 %), with no treatment-related deaths, supporting further investigation of this regimen.
10.1186/s12916-026-04867-z
Aging is associated with the outcomes of immune checkpoint blockade in renal cell carcinoma.
J IMMUNOTHER CANCER · Q1 JOURNAL - RANK #12/183TOP-TIER
This pooled analysis of individual participant data from two randomized controlled trials, CheckMate 214 and JAVELIN Renal 101, evaluated the impact of aging on immune checkpoint inhibitor outcomes in advanced renal cell carcinoma. Among 1926 patients, 964 received ICIs and 962 received sunitinib, with an optimal age cutoff of 60 years. Young patients (<60) showed significant overall survival benefit with ICIs (HR=0.70, 95% CI 0.56-0.87, p<0.001), while those over 60 had marginal benefit (HR=0.82, 95% CI 0.67-1.00, p=0.05), and patients ≥75 showed no benefit (HR=1.05, 95% CI 0.62-1.79, p=0.85). The authors conclude that immunotherapy advantage diminishes with age, requiring individualized treatment decisions for older patients.
10.1136/jitc-2025-014605
Fianlimab, a human lymphocyte activation gene-3 monoclonal antibody, in combination with cemiplimab: Tumor-specific expansion cohorts in advanced malignancies.
CANCER-AM CANCER SOC · Q1 JOURNAL - RANK #68/326
This phase 1 dose-expansion study evaluated fianlimab (anti-LAG-3) plus cemiplimab (anti-PD-1) in patients with advanced NSCLC, ccRCC, HNSCC, and CSCC. Patients received 1600 mg fianlimab plus 350 mg cemiplimab every 3 weeks for up to 24 months, with ORR per RECIST 1.1 as the primary endpoint. Investigator-assessed ORR was 27% in NSCLC-N, 7% in NSCLC-E, 20% in ccRCC-N, 7% in ccRCC-E, 33% in HNSCC-N, 7% in HNSCC-E, and 20% in CSCC-E. The combination demonstrated modest efficacy with acceptable safety, warranting further investigation.
10.1002/cncr.70396
Stereotactic body radiotherapy plus sunitinib vs. sunitinib alone in treatment-naive oligometastatic renal cell carcinoma: A phase 2 clinical trial.
CELL REP MED · Q1 JOURNAL - RANK #15/195TOP-TIER
This single-center, phase 2 non-randomized controlled trial evaluated adding SBRT to sunitinib versus sunitinib alone in treatment-naive oligometastatic RCC, with patients choosing their arm. The primary endpoint ORR favored SBRT (83.3% vs 29.2%; p<0.001); median follow-up was 40.6 months and 1-year local control was 91.5%. PFS was longer with SBRT (17.3 vs 6.3 months; p=0.036), and post hoc multivariable analysis confirmed benefit (HR 0.42; 95% CI 0.21–0.84; p=0.015). Grade 3 toxicities were similar (54.2% vs 50.0%; p=0.773), with a trend toward better quality of life in the SBRT arm, supporting further confirmation in phase 3 trials.
10.1016/j.xcrm.2026.102747
Phase II Trial of Ixazomib Combined with Gemcitabine and Doxorubicin in Patients with SMARCB1-Deficient Renal Medullary Carcinoma.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This single-center, single-arm, phase II trial (NCT03587662) evaluated ixazomib plus gemcitabine and doxorubicin in 30 patients with SMARCB1-deficient renal medullary carcinoma, dosing every 2 weeks for up to 13 cycles followed by ixazomib/gemcitabine maintenance. Coprimary endpoints were ORR and 28-week DCR versus historical gemcitabine+doxorubicin; secondary endpoints included PFS, OS, and safety, with integrated single-cell and bulk multi-omics correlative analyses in 11 patients. ORR was 36% (95% CrI, 21%-54%) with a 91.4% probability of exceeding historic doublet therapy, but 28-week DCR was 17% (95% CrI, 6%-31%), crossing the predefined futility boundary; median PFS and OS were 3.5 and 7.4 months, respectively, and grade ≥3 toxicities were mainly hematologic (thrombocytopenia 20%, leukopenia 17%). The regimen modestly improved response but did not extend disease control; correlative profiling suggested immune-inflamed states predicted response and stromal-myeloid/proteostasis pathways were associated with resistance.
10.1158/1078-0432.CCR-25-4518
Apr 06 – Apr 13, 2026
Belzutifan Efficacy in Von Hippel-Lindau Disease-Associated Renal Cell Carcinoma Versus Natural History Control Arm.
JNCI-J NATL CANCER I · Q1 JOURNAL - RANK #44/326
This study used an external control arm (ECA) to interpret results of a single-arm trial (LS-004) evaluating belzutifan in 61 patients with VHL RCC. In LS-004, median follow-up was 37.8 months and the overall response rate was 64% (95% CI=50.6 to 75.8). Researchers compared these outcomes to an ECA of 244 VHL RCC patients undergoing active surveillance, balanced via propensity scoring (SMD<0.1), yielding an adjusted ORR of 63.9% in LS-004 vs 1.5% in ECA and a median time to surgery of 51.3 months in ECA but not yet reached in LS-004. The authors conclude that belzutifan likely provides substantial efficacy in VHL RCC, with the large difference compared to ECA unlikely due to chance.
10.1093/jnci/djag064
Simlukafusp alfa (FAP-IL2v) plus atezolizumab with or without bevacizumab in unresectable, metastatic renal cell carcinoma: a randomized, open-label phase Ib study.
J IMMUNOTHER CANCER · Q1 JOURNAL - RANK #12/183TOP-TIER
This randomized, open-label phase Ib study evaluated the efficacy, safety, and pharmacodynamics of simlukafusp alfa (FAP-IL2v) combined with atezolizumab with or without bevacizumab in patients with unresectable, metastatic renal cell carcinoma. The study employed a dose escalation and extension design across multiple arms, enrolling 66 treatment-naïve or pretreated patients, with primary objectives of determining the recommended FAP-IL2v dose and assessing antitumor activity. Key findings included objective response rates of 25% for the doublet therapy and 47% for the triplet therapy, with median progression-free survival of 6.3 and 18.3 months, respectively, and a recommended FAP-IL2v dose of 10 mg. The principal conclusion was that the combination therapies demonstrated safety profiles consistent with individual drugs and showed promising efficacy, particularly for the triplet regimen, supporting further research based on pharmacodynamic results aligned with the IL-2 mechanism of action.
10.1136/jitc-2025-012466
Cabozantinib in patients with non-locally pretreated brain metastases from renal cell carcinoma: Results of the multicenter phase II trial CABRAMET.
EUR J CANCER · Q1 JOURNAL - RANK #45/326
The CABRAMET trial was a multicenter, prospective, open-label phase II study designed to evaluate the efficacy of cabozantinib, a VEGFR tyrosine kinase inhibitor, in patients with non-locally pretreated brain metastases (BM) from renal cell carcinoma (RCC). It included 26 RCC patients with BM and fewer than three prior systemic treatments (excluding cabozantinib), who received an oral dosage of 60 mg/day. The study found a 6-month progression-free rate (6m-BM-PFR) of 56%, an overall BM objective response rate (ORR) of 61.5%, and a median BM progression-free survival of 10.7 months, with median overall survival of 15.0 months. These results demonstrated cabozantinib’s efficacy and tolerability in this patient cohort, positioning it as a promising treatment for this challenging population.
10.1016/j.ejca.2026.116712
Mar 30 – Apr 06, 2026
KIM-1 in Advanced Papillary and Clear Cell Renal Cell Carcinoma.
EUR UROL · Q1 JOURNAL - RANK #3/133TOP-TIER
This prospective multi-arm trial evaluated durvalumab alone or in combination with tremelimumab or savolitinib in patients with metastatic clear cell and papillary renal cell carcinoma, aiming to explore KIM-1 levels. Circulating KIM-1 was measured in 123 patients with ccRCC and 31 patients with pRCC, showing higher levels in pRCC compared to ccRCC (7835 vs 5470 pg/ml, p=0.05). Lower KIM-1 correlated with better radiological responses in pRCC (p=0.025), and higher baseline KIM-1 was associated with poorer overall survival in ccRCC (HR 1.77, 95% CI 1.15-2.72, p=0.01). These exploratory findings suggest KIM-1 may be a useful biomarker in advanced ccRCC and pRCC.
10.1016/j.eururo.2026.03.005