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Peer-To-Peer Clinical Conversation |
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PDIGREE Trial Tests Adaptive Immunotherapy Approach for Metastatic Kidney Cancer
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Tian Zhang, MD, MHS
Pedro Barata speaks with Tian Zhang about the PDIGREE phase III adaptive trial. This cooperative group study enrolled over 1,000 patients across 46 states over five years, representing a collaborative effort between community oncology and academic centers. |
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Highlights from the 2025 American Society of Clinical Oncology Annual Meeting |
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| Targeting HIF-2α: A New Frontier in Renal Cell Cancer Therapy |
| Rana McKay, MD |
| Rana McKay highlighted HIF-2α as a validated and emerging therapeutic target in ccRCC, driven by loss of VHL function. Belzutifan, the first approved HIF-2α inhibitor, showed meaningful efficacy across multiple LITESPARK trials, both as monotherapy and in combination, with additional promising agents like casdatifan and NKT2152 in development. These therapies demonstrate manageable on-target toxicity and represent a growing frontier in RCC treatment beyond VEGF and immune checkpoint inhibitors. |
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| Biomarkers in Kidney Cancer: Are We There Yet? |
| W. Kimryn Rathmell, MD, PhD |
| Kimryn Rathmell emphasized that while biomarkers are central to understanding kidney cancer subtypes and guiding diagnostics, their predictive utility for treatment selection remains limited. Emerging tools like gene expression signatures (GES), spatial biology, and single-cell RNA sequencing show promise—especially as explored in trials like OPTIC—but the field is still evolving, with no definitive predictive biomarker yet established for routine use. |
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| Exploratory Analysis from NEOAVAX, a Neoadjuvant Trial of Avelumab/axitinib in Patients with Localized Renal Cell Carcinoma Who Are at High Risk of Relapse After Nephrectomy |
| Axel Bex, MD, PhD |
| Axel Bex presented an exploratory analysis of the NEOAVAX trial, which tested neoadjuvant avelumab and axitinib in high-risk, non-metastatic clear cell RCC. While radiologic and pathologic responses were not strongly correlated, patients with major pathologic responses had longer disease-free survival and showed enriched immune cell infiltration, particularly CD8+CD39+ T-cells, suggesting potential biomarkers for prognosis and future adaptive perioperative trials. |
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| An Integrative Analysis of Circulating and Tumor Microenvironment Determinants of Patient Response in the Checkmate 9ER Trial of Nivolumab and Cabozantinib in Advanced Renal Cell Carcinoma |
| David Braun, MD, PhD |
| David Braun presented an integrative biomarker analysis from the CheckMate-9ER trial, combining tumor microenvironment, circulating biomarkers, and AI-based image analysis to better predict response to nivolumab + cabozantinib in advanced RCC. Higher tumor endothelial cell content and lower circulating extracellular matrix markers were associated with improved outcomes, and a multivariable machine learning model incorporating 16 features outperformed single biomarker approaches. |
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| Gut-Associated Checkpoint as a Prognostic Biomarker in Metastatic Renal Cell Carcinoma (mRCC): Results from a Randomized First-Line Clinical Trial |
| Renee Saliby, MD, MSc |
| Renee Saliby presented data showing that soluble MAdCAM-1, a gut-associated checkpoint marker, is a strong prognostic biomarker in metastatic RCC, with higher levels linked to significantly better progression-free and overall survival across treatment arms in the JAVELIN Renal 101 trial. The findings support the role of the gut microbiome in modulating treatment outcomes and suggest that patients with low MAdCAM-1 levels might benefit from microbiota-targeted therapies. |
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| Nivolumab plus Ipilimumab vs Sunitinib for First-Line Treatment of Advanced Renal Cell Carcinoma: Final Analysis from the Phase 3 CheckMate 214 Trial |
| Robert Motzer, MD |
| Robert Motzer presented the final 9-year follow-up results from the phase III CheckMate 214 trial, confirming that nivolumab + ipilimumab continues to provide durable overall survival, progression-free survival, and response benefits over sunitinib in treatment-naïve advanced renal cell carcinoma, particularly in intermediate/poor-risk patients. The combination also showed a favorable long-term safety profile, with fewer severe adverse events compared to sunitinib, reinforcing its role as a standard first-line therapy. |
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| Combination Casdatifan plus Cabozantinib Expansion Cohort of Phase 1 ARC-20 Study in Previously Treated Patients with Clear Cell Renal Cell Carcinoma
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| Toni Choueiri, MD, FASCO
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| Toni Choueiri presented data from the ARC-20 phase 1 expansion cohort evaluating casdatifan (a novel HIF-2α inhibitor) plus cabozantinib in previously treated clear cell renal cell carcinoma (ccRCC) patients. The combination demonstrated a confirmed objective response rate of 46% with a manageable safety profile, including mostly low-grade anemia and fatigue. These promising results support further investigation of casdatifan in ccRCC treatment settings. |
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| Hypoxia-Inducible Factor-2α (HIF-2α) Inhibitor Belzutifan in Von Hippel-Lindau (VHL) Disease–associated Neoplasms: 5-Year Follow-up of the Phase 2 LITESPARK-004 Study |
| Vivek Narayan, MD, MS |
| Vivek Narayan presented 5-year follow-up data from the LITESPARK-004 trial, showing that belzutifan continues to provide durable and clinically meaningful responses in von Hippel-Lindau (VHL) disease–associated tumors. The objective response rates were 70% for RCC, 50% for CNS hemangioblastomas, and 90% for pNETs, with high rates of maintained response and reduced need for surgery, and no new safety concerns observed over the extended follow-up. |
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| ALLO-316 in Advanced Clear Cell Renal Cell Carcinoma (ccRCC): Updated Results from the Phase 1 TRAVERSE Study
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| Samer Ali Srour, MBChB, MS
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| Samer Srour presented updated phase 1b results from the TRAVERSE study evaluating ALLO-316, an off-the-shelf CD70-targeting allogeneic CAR T therapy, in heavily pretreated patients with advanced clear cell RCC. In patients with high CD70 expression, ALLO-316 showed a 25% objective response rate with durable responses, including one exceeding a year, and a manageable safety profile. The results support the continued development of ALLO-316 and highlight its potential as a breakthrough CAR T therapy for solid tumors.
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