Renal cell carcinoma (RCC) is the most common kidney cancer in adults, and while it is often caught incidentally on imaging at an early stage, advanced disease has historically been hard to treat. Immunotherapy combinations have transformed outcomes for metastatic disease in recent years.
What's actually going on in research
Combining two checkpoint inhibitors, or a checkpoint inhibitor with an anti-VEGF tyrosine kinase inhibitor (TKI), has become standard first-line treatment for advanced RCC, with some patients achieving long-term remissions. HIF-2alpha inhibitors represent a new approach that specifically targets the genetic driver of the most common clear cell RCC subtype. Adjuvant trials following nephrectomy are now offering systemic therapy to patients at high risk of recurrence.
Checkpoint plus TKI combinations
Pairing immune checkpoint inhibitors with anti-VEGF drugs like axitinib or cabozantinib produces better outcomes than either alone for advanced clear cell RCC.
HIF-2alpha inhibitors
Belzutifan targets HIF-2alpha — the key molecular driver of clear cell RCC — producing durable responses and now being tested alongside standard therapies in earlier settings.
Adjuvant immunotherapy
Following kidney removal, pembrolizumab reduces the risk of recurrence in high-risk patients. Trials are comparing adjuvant strategies and testing novel agents in this setting.
What to know before you search
Eligibility depends on RCC histologic subtype (clear cell vs. non-clear cell), risk group (favorable vs. poor), prior treatment, and specific molecular features.
What types of trials are currently open
- Treatment trials — Testing new drug combinations or sequences for advanced or metastatic renal cell carcinoma.
- Adjuvant trials — Testing post-surgery drug therapy to prevent recurrence in high-risk localized RCC.
- Targeted therapy trials — Evaluating HIF-2alpha inhibitors, mTOR inhibitors, and VEGFR inhibitors in clear cell and non-clear cell subtypes.
- Surgical trials — Comparing partial vs. radical nephrectomy and cytoreductive surgery timing in metastatic disease.
- Biomarker trials — Identifying predictors of response and resistance in RCC to guide treatment selection.
Recently added Renal Cell Carcinoma trials
Pilot Study of Bone Mineral Density Changes During Anti-PD-1 Immunotherapy
Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment and work by blocking protein interactions that normally prevent the immune system from recognizing and destroying cancer cells. However, these agents, now approved for over 15 types of cancers and for both early-stage and metastatic disease, are capable of causing inflammation in any organ system of the body that can lead to organ damage, dysfunction, and even death in rare cases. Some patients may suffer acute and treatable complications like joint pain, but some may have irreversible complications like hypothyroidism that requires daily, life-long medication. It is therefore important to fully understand the different types of damage ICIs can cause to better monitor patients receiving ICI therapy. A rising concern from recent reports in the literature is that ICIs may weaken bone and increase the risk of fractures. In this study, the investigators aim to characterize how ICIs impact the bone by examining several factors in patients undergoing curative-intent ICI treatment either alone or in combination with chemotherapy: bone mineral density, bone volume, and markers of bone turnover in the blood. The study will use two imaging techniques to assess bone mineral density and volume. DXA (dual X-ray absorptiometry) imaging uses low-dose X-rays to measure how dense (or strong) bones are and is often used to diagnose or assess the risk of osteoporosis. High-resolution peripheral quantitative computed tomography (HRpQCT) is a 3D imaging technology that can quantify bone structure and volume and offers high resolution that can be used to assess bone in smaller bones of the peripheral skeleton. The investigators hypothesize that ICI treatment will weaken bones and increase the risk of fractures. As ICI therapy is relatively new, a rising number of patients may be at risk of fractures or have low bone density that is not being monitored because there are no guidelines in place notifying physicians of this potential risk to patients. This is study will provide important preliminary data that will be the basis for larger studies in the future aiming to better monitor and potentially treat bone weakening in patients treated with ICIs to reduce the pain, inconvenience, and complications from fragility fractures.
Dual-target CD70/CAIX CAR-NK Cells for Advanced Clear Cell Renal Cell Carcinoma
Phase 1/2 study evaluates the safety, feasibility, and preliminary antitumor activity of allogeneic dual-target CD70/CAIX CAR-NK cells after fludarabine/cyclophosphamide lymphodepletion in adults with advanced or metastatic clear cell RCC that has progressed after standard therapy. The study is designed to determine a recommended dose and schedule, characterize hepatobiliary safety, and explore whether CD70-high, CAIX-high, or dual-high tumors derive the greatest benefit. Biomarker-defined activity signals will be used to guide whether later development should prioritize CD70, CAIX/CA9, or continued dual-targeting.
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