What's New in Kidney Cancer Research

Welcome back to our blog series about kidney cancer clinical trials where we break down recent research into key updates for patients and others interested in advances in the field from the major cancer conferences including the 2024 American Society of Clinical Oncology’s (ASCO) annual meeting, the 2024 European Society for Medical Oncology (ESMO) annual meeting, the 2025 ASCO genitourinary focus meeting (ASCO GU), as well as the Kidney Cancer Association’s own International Kidney Cancer Symposiums (IKCS).

While 2024 was somewhat quiet in terms of groundbreaking kidney cancer advancements, research remains incredibly active with several promising findings.  

Since January 1, 2024, an impressive 79 new clinical trials have opened and currently enrolling, a testament to the relentless pursuit of better treatments. Although we’re still waiting for that definitive cure, there are some good, less good news, and exciting concepts to share. As we did in our first blog, we will highlight some terms along the way to help you decode some of the clinical trial language and try to highlight for each study why this is important. So, without further ado, let’s dive deeper into the most intriguing developments since our last review in May 2024.

One highly anticipated trial, SUNNIFORECAST, was showcased at ESMO 2024. This study was important because it evaluated, for the first time, the efficacy of immunotherapy—specifically the combination of ipilimumab and nivolumab (IPI-NIVO)—for patients with non-clear cell renal cell carcinoma (nccRCC). Historically, nccRCC subtypes have been underrepresented in kidney cancer research, receiving far less attention compared to clear cell RCC (ccRCC), and this was the first study that enrolled over 300 nccRCC patients.

The results were remarkable and encouraging. Patients receiving IPI-NIVO experienced significantly improved survival rates. Specifically, the combination increased the one-year overall survival (OS) rate to 86.9%, compared to 76.8% with standard treatments, a notable advancement for these underserved patient groups. The median OS also improved dramatically from 33.9 months to 42.4 months. While progression-free survival (PFS) was similar between groups, the overall response rate, indicating tumor shrinkage, was considerably better at 32.8% compared to just 19.6% in patients receiving traditional therapies.

Interestingly, sub-analyses showed that patients whose tumors expressed the biomarker PD-L1 protein and those with lymph node metastases benefited even more, highlighting potential patient-specific markers that might predict treatment success. Among various nccRCC subtypes, patients with papillary and non-papillary RCC showed the most improvement. However, the chromophobe RCC subgroup gained less benefit, emphasizing the need for more targeted research within these specific subtypes. Despite the numbers telling a clear story of a meaningful shift towards better survival, the fact that the nccRCC population included a complex mix of different histology and standard treatments in the control group, interpreting the results has raised quite a debate among experts that would like to see more studies like SUNNIFORECAST that could answer more precise questions for specific kidney cancer subtypes.

Another eagerly awaited study, TiNivo-2, also reported findings at ESMO 2024. It tested the combination of tivozanib, an approved tyrosine kinase inhibitor (TKI)—a drug that blocks enzymes responsible for cancer cell growth—with nivolumab, a checkpoint inhibitor immunotherapy, against tivozanib alone. The scientific community was keenly interested to determine if adding immunotherapy could further improve patient outcomes, especially in cases previously treated with immunotherapy, a strategy known as immunotherapy rechallenge.

Contrary to expectations, this combination did not yield significantly better results. The median progression-free survival was similar in both groups, indicating no substantial advantage to adding nivolumab to tivozanib. Preliminary overall survival data also suggested minimal differences between groups, highlighting that single-agent tivozanib remains effective, particularly as a well-tolerated later-stage therapy. Patients also experienced more side effects when combining these two drugs, underscoring the importance of evaluating the benefit-risk balance in treatment decisions. This insight provides valuable guidance on the limitations of immunotherapy rechallenge in certain patient groups.

Understanding biomarkers to predict treatment response remains one of kidney cancer research’s greatest challenges. Exciting progress was presented at ASCO GU 2025 through the CheckMate 214 trial, investigating kidney injury marker-1 (KIM-1) as a potential predictive biomarker. KIM-1, detectable in blood samples, has previously been linked to kidney cancer prognosis. Researchers measured KIM-1 levels before and after initiating nivolumab and ipilimumab therapy, observing astonishing outcomes.

Patients with a significant decrease (over 30%) in KIM-1 after a single treatment cycle experienced dramatically improved outcomes, achieving median progression-free survival of 70.8 months compared to just 4.2 months in those whose KIM-1 levels increased significantly. Similarly, overall survival was substantially better at 85.4 months versus 26.6 months. These compelling findings position KIM-1 as a highly promising biomarker, potentially revolutionizing how doctors personalize treatment and helping patients avoid ineffective therapies.

Further good news emerged from ASCO GU 2025, where the COSMIC-313 trial provided key updates on a triple therapy combination: cabozantinib, nivolumab, and ipilimumab (C+N+I). This potent regimen significantly improved progression-free survival to 16.6 months compared to 11.2 months with nivolumab and ipilimumab alone. Response rates also notably increased, offering robust proof of the combination’s effectiveness. Despite these gains, overall survival remained comparable between groups, highlighting the continued necessity for further research and refinement in treatment strategies. Nonetheless, COSMIC-313’s manageable safety profile makes this triple combination an appealing and viable treatment option for advanced RCC patients, enhancing their quality of life by significantly delaying disease progression.

CheckMate 9ER also delivered reassuring long-term outcomes for nivolumab plus cabozantinib at ASCO GU 2025, firmly establishing this combination as a leading therapy in advanced RCC. Patients benefited greatly, experiencing substantial improvements in progression-free survival (16.4 months versus 8.3 months) and overall survival (46.5 months versus 35.5 months) compared to standard sunitinib treatment, alongside significantly better response rates. This study underscores the durability and effectiveness of the nivolumab-cabozantinib regimen.

Read more about ASCO GU 2025 here.

Finally, we turn to a promising newcomer, Casdatifan, a novel HIF-2α inhibitor. At ASCO 2025, researchers presented encouraging results from the ARC-20 study in patients whose cancers progressed despite previous treatments. Casdatifan demonstrated a 34% tumor shrinkage rate in patients receiving higher doses, with particularly notable benefits in those classified with favorable risk factors, meaning patients with certain clinical characteristics known to indicate better outcomes. The drug was generally well-tolerated, with manageable side effects such as mild anemia and occasional low oxygen levels.

You may wonder why this is exciting, especially since belzutifan is an approved drug with the same mechanism of action. Well, having Casdatifan or any other drug as an alternative to the only available option on the market could bring several advantages for patients, including an expanded spectrum of efficacy due to differences in how the drugs work, a potentially different side effect profile for some patients, and most importantly, reducing financial toxicity. Having multiple drugs in the same class can lead to better competition, potentially lowering costs and improving insurance coverage, making treatment more accessible to those in need.

Exciting New Trials on the Horizon

An ongoing trial ( Clinical Trial NCT06318871) is testing an innovative approach using cytokine-induced memory-like (CIML) natural killer (NK) cells. Unlike traditional therapies, this trial introduces a new immune-based strategy that differs from chimeric antigen receptor T-cell (CAR-T) cell therapy, which has struggled to treat solid tumors like kidney cancer.

CAR-T therapy has transformed blood cancer treatment but faces challenges in solid tumors due to the tumor’s harsh environment. This trial takes a different approach, enhancing NK cells with cytokines to boost their cancer-fighting ability before reintroducing them into the patient. Unlike CAR-T, this method is designed to be more accessible, scalable, and potentially safer for advanced RCC patients.

This is the first time CIML NK cells are being tested in combination with low-dose IL-2, a cytokine that activates immune cells, in patients with advanced clear cell renal cell carcinoma and urothelial carcinoma.

This breakthrough was made possible by a 2021 Kidney Cancer Association Research Award to Dr. Toni Choueiri and Dr. Rizwan Romee at the Dana-Farber Cancer Institute, which helped move this concept from research to clinical testing. If successful, this therapy could provide a new option for patients who have exhausted other treatments, potentially improving survival and quality of life. Trials like this represent the future of cancer care—more precise, innovative, and patient-focused. Read an update about this research HERE.

How to Stay Informed and Get Involved

I hope this update helped enrich your understanding of new kidney cancer research – please share your thoughts with us! Staying informed and potentially getting involved in clinical trials can be a pivotal part of navigating your kidney cancer journey. Patients and caregivers play a pivotal role in the success of clinical trials. By participating, you contribute to the advancement of medical knowledge and help future patients receive better care. If you’re considering joining a trial, we encourage discussing it with your healthcare provider to understand how it might fit into your treatment plan.

Additional Resources: