Kidney Cancer Highlights from ASCO 2025
We rounded up a few research highlights from the 2025 American Society of Clinical Oncology meeting, held recently in Chicago, IL.
Long-Term Trial Results
Ipi/Nivo combo remains superior to sunitinib after a decade of data
After an average 9 years of follow-up – the longest reported follow-up data from an immunotherapy combination treatment in renal cell carcinoma (RCC) – final results from the phase 3 CheckMate-214 trial continue to support ipilimumab plus nivolumab as standard first-line therapy in patients with previously untreated advanced or metastatic kidney cancer due to it’s long-term survival benefits. Benefits were seen for all patients including favorable risk ones.
The trial compared ipilimumab plus nivolumab to sunitinib, an older-generation targeted therapy. Probability of survival was 31% after 9 years on combination therapy compared with 20% with sunitinib. Complete response rates were higher and average length of response to treatment was longer in the combination therapy group and side effects were manageable.
Nivolumab plus ipilimumab was FDA approved in 2018 as first-line therapy for people with advanced renal cell carcinoma after CheckMate 214 demonstrated benefit over sunitinib after about 2.5 years of follow up. [ASCO 2025, Abstract 4505]
Adjuvant pembrolizumab continues to show benefit post-surgery in patients with a high risk of recurrence
Adjuvant treatment may be given after kidney surgery to prevent cancer cells from continuing to grow, ie preventing recurrence. The immunotherapy pembrolizumab was FDA-approved for adjuvant treatment of RCC in 2021 based on the results of the KEYNOTE-564 trial. Compared to a placebo group, kidney cancer patients at high-risk of recurrent cancer after surgery who were treated with pembrolizumab for up to one year had a longer period of disease-free survival. Although some of the key outcome measures were not mature at the time, the results supported an adjuvant treatment strategy.
At ASCO 2025, 5-year results of KEYNOTE-564 continued to demonstrate superior outcomes in patients who were treated with adjuvant pembrolizumab compared with placebo in this patient population with a high likelihood of recurrence following surgery. Over about 70 months of follow up, the placebo group’s average disease-free survival time was 5 years and 8 months, after which time cancer had recurred and was detected again. Disease-free survival was not reached in the adjuvant pembrolizumab group, meaning these patients remained cancer-free during the follow up period. All patients stopped receiving pembrolizumab within 3 years and no new treatment-related side effects were reported during the follow up period. [ASCO 2025, Abstract 4514]
More Evidence for New Treatments
Zanzalitinib is a new targeted therapy
Zanzalitinib is a new targeted therapy – a VEGFR TKI – that prevents blood vessel growth to tumors, cancer spread, and immune system suppression. In combination with nivolumab in a phase 1 trial, zanzalitinib showed anticancer activity and patients given this regimen experienced both partial and complete responses. At 12 months of follow up, almost 2/3 of patients had stable or improved cancer status.
The phase 1b STELLAR-002 trial included 80 patients with untreated advanced kidney cancer who could not get surgery. In addition to the zanzalitinib/nivolumab group, there was a triplet therapy group treated with zanzalitinib, nivolumab, and relatimab. However, the addition of relatimab did not seem to provide extra benefit. Zanzalitinib was also associated with a low rate of hand and foot syndrome. [ASCO 2025, Abstract 4515]
Casdatifan is a promising new HIF-2a treatment
HIF-2a is a new type of anti-cancer treatment that targets oxygen regulation as a way to prevent cancer growth. Belzutifan is the only HIF-2a currently approved to treat certain kidney cancers but more are being studied.
Casdatifan is a new HIF-2a treatment that had promising results in a phase 1 trial when used in combination with the VEGFR-TKI cabozantinib. The study included 27 people with clear cell kidney cancer who had already been treated with immunotherapy or a VEGFR-TKI targeted therapy; 41% of patients responded to treatment with the casdatifan/cabozantinib combination treatment. The current results suggest casdatifan should advance to phase 2 and 3 trials for continued testing. [ASCO 2025, Abstract 4506]
New CAR T cell treatment for RCC
Updated results from the phase 1 TRAVERSE study on a type of immunotherapy that modifies human T cells to make them more effective showed benefit for most patients with advanced kidney cancer. TRAVERSE was initially presented at the KCA’s 2024 International Kidney Cancer Symposium: North America.
Chimeric antigen receptor (CAR) T cell therapy uses extracted immune cells – T cells – that are changed to recognize and attack cancer cells better. ALLO-316 is the CAR T cell therapy used in the TRAVERSE study, which included 39 kidney cancer patients who had received prior treatment. After a single dose of ALLO-316, 31% of patients responded to treatment and 4 out of 5 have ongoing response after an average of 7 months and including over a year post-treatment. The researchers reported a manageable and consistent safety profile although most patients – 96% – did experience severe or life-threatening side effects and there were three deaths. The results support further use of CAR T cell therapy in certain solid tumors such as RCC.
Biomarkers
Multiple new RCC biomarkers in trials
“Biomarkers” include a wide array of ways to understand a tumor. Biomarkers can include specific genes, proteins, information seen on CT or MRI scans, and liquid biopsies – blood tests to identify the contents of what is circulating in our blood.
In her introduction to a session on emerging RCC biomarkers at ASCO 2025, Dr. W. Kimryn Rathmell of The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute explained that information from biomarkers is already essential for defining tumors. In kidney cancer, that means they help understand characteristics of some kidney tumors that might help with diagnosis and prognostic care.
There are several new biomarkers being tested in clinical trials that could help doctors determine the most effective cancer treatment based on characteristics of the tumor and/or the patient.
The session presenters described several studies of biomarkers in early stages of investigation including those that might predict patient outcomes after first instance of treatment with immunotherapy, determine whether or not patients would respond to neoadjuvant therapy (typically given to manage a tumor before surgery to remove it), understand the influence of certain proteins in the gut microbiome, and identify tumor characteristics of people who had varying responses to kidney cancer treatment. [ASCO 2025, Abstract 4509, Abstract 4511, Abstract 4512]
The biomarker with the strongest evidence for continued study and potential further use is kidney injury molecule-1 (KIM-1). Prior analysis of the IMmotion101 trial presented at ASCO 2024 showed that the amount of KIM-1 protein that is detectable in blood samples is associated with predicting RCC disease recurrence after surgery, identifying patients that might benefit from treatment with atezolizumab after surgery. A more recent analysis of this trial presented at ASCO 2025 showed the existence of genetic changes in tumors that progressed after adjuvant atezolizumab, which could help explain why some people relapse, in addition to information from biomarkers like KIM-1. [ASCO 2025, Abstract 4510]
Rathmell stressed that an integrated approach to future biomarker discovery and development, combining multiple types and aspects of biomarkers, is the path to “enable risk assessment, early detection, and ultimately – prevention.”
Translocation RCC
Combination therapy shows activity in advanced tRCC but trial size remains small
Translocation RCC is a rare type of kidney cancer that accounts for about 50% of pediatric RCC cases and 1-5% of RCC cases overall. tRCC is often aggressive and currently there is no standard of care for treatment.
The phase 2 AREN1721 trial aimed to enroll 28 patients – adults and children – with advanced metastatic tRCC or advanced tRCC that was not possible to remove surgically for treatment with the immunotherapy/targeted therapy combination of nivolumab plus axitinib or treatment with nivolumab alone.
Despite what the researchers called “aggressive” recruitment strategies, the trail only included 13 eligible patients between 2013-2023. Their median age was 16 years. Patients were not eligible if they were exposed to immune-blocking anti-PD1/PDL1 drugs like nivolumab or to axitinib, which is an anti-VEGF drug that prevents blood vessel growth, prior to enrollment.
Six of the patients were randomized to combination nivolumab/axitinib treatment, 2 to axitinib alone, and 5 to nivolumab alone. Among patients given nivolumab/axitinib, 33% had a partial response to treatment, compared with 0% in the single-agent groups, and no primary disease progression. The combination group also had improved progression-free survival and overall survival.
Statistically, the researchers concluded that nivolumab/axitinib combination therapy was more active than nivolumab alone, which appeared inactive. However, because the trial was so small, it was not possible to determine if the addition of an anti-PD1 inhibitor like nivolumab added to anti-VEGF therapy adds benefit. Further research and better trial recruitment are needed. [ASCO 2025, Abstract 4521]