As anticipation builds for the 2026 Genitourinary (GU) Cancers Symposium, OncLive® asked leading kidney cancer specialists to share the renal cell carcinoma (RCC) research topics and abstracts they are most eager to see at this year’s meeting, including late-phase updates that may refine adjuvant strategies and reshape post–PD-(L)1 treatment sequencing.
We gathered exclusive insights from:
- Jad Chahoud, MD, MPH, chief scientific and innovation officer at Orlando Health Cancer Institute in Florida
- Guru Sonpavde, MD, medical director for GU Oncology, assistant director of the Clinical Research Unit, and the Christopher K. Glanz Chair for Bladder Cancer Research at AdventHealth Cancer Institute in Orlando, Florida
- Axel Merseburger, MD, PhD, professor of urology and head of the Department of Urology at University Hospital Schleswig-Holstein in Germany
Several pivotal clear cell RCC (ccRCC) studies will be in focus at ASCO GU 2026, offering data that could inform both resected and advanced disease paradigms. These include the randomized phase 3 LITESPARK-022 trial (NCT05239728), evaluating adjuvant pembrolizumab (Keytruda) plus belzutifan (Welireg) vs pembrolizumab alone in patients with high-risk ccRCC following nephrectomy, including stage II/III and post–metastasectomy (M1 NED) populations; experts are closely watching the magnitude of disease-free survival (DFS) benefit and the trajectory of longer-term outcomes as overall survival matures.1
Also drawing significant attention is the open-label phase 3 LITESPARK-011 study (NCT04586231), which is comparing belzutifan plus lenvatinib (Lenvima) vs cabozantinib (Cabometyx) in patients with advanced RCC who have experienced disease progression on or after anti–PD-(L)1 therapy; beyond the extent of progression-free survival (PFS) improvement, the experts highlighted the importance of tolerability and patient-reported outcomes with a doublet approach, alongside broader considerations such as cost and value in real-world adoption.2
Importantly, patient-reported outcomes and quality-of-life signals in resected RCC remain a key theme, including ongoing interest in active monitoring vs durvalumab (Imfinzi) or durvalumab plus tremelimumab-actl (Imjudo) adjuvant strategies in the phase 3 RAMPART trial (NCT03288532).
Read more below on the abstracts experts are most anticipating at this year’s meeting.
Adjuvant pembrolizumab plus belzutifan versus pembrolizumab for clear cell renal cell carcinoma (ccRCC): The randomized phase 3 LITESPARK-022 study
Chahoud: The first [study I am looking forward to seeing] is an adjuvant clinical trial for [patients] with stage II/III, [or] M1 NED ccRCC, with the current [standard] of care that was recently FDA approved, pembrolizumab, on one arm, and pembrolizumab plus belzutifan, which is a HIF-2α inhibitor, in the other arm. [Belzutifan] is FDA-approved in second line and beyond for [patients with] metastatic disease. However, [in this LITESPARK-022], this combination was moved down to the adjuvant setting, where adjuvant pembrolizumab [was recently FDA-approved].
This [data from LITESPARK-022] will focus on the primary end point of this clinical trial, which is DFS, although overall survival [OS] data are not mature yet at this time point. There’s been an announcement that the DFS primary end point has been met.
Sonpavde: A recent press release reported that the study demonstrated improved DFS for pembrolizumab plus belzutifan vs pembrolizumab plus placebo in the adjuvant setting following nephrectomy for high-risk ccRCC; [therefore], these results are eagerly anticipated.
Belzutifan (bel) plus lenvatinib (lenva) versus cabozantinib (cabo) for advanced renal cell carcinoma (RCC) after anti–PD-(L)1 therapy: Open-label phase 3 LITESPARK-011 study
Chahoud: LITESPARK-011 is a trial comparing lenvatinib plus belzutifan [vs] cabozantinib [in the second line and beyond]. [Cabozantinib monotherapy] currently dominates the second-line market. It’s a head-to-head comparison between the combination of lenvatinib and belzutifan vs cabozantinib.
RCC Studies to Watch at ASCO GU 2026
- Adjuvant intensification in ccRCC: LITESPARK-022 evaluated pembrolizumab plus belzutifan vs pembrolizumab alone after nephrectomy in high-risk stage II/III and M1 NED disease. The DFS primary end point was met.
- Post–PD-(L)1 head-to-head sequencing: LITESPARK-011 compared belzutifan plus lenvatinib vs cabozantinib, in the second-line setting and beyond, and the combination produced a reported PFS benefit.
- Patient-centered perioperative decision-making: RAMPART is informing how active monitoring compares with durvalumab–based adjuvant strategies ± tremelimumab, keeping quality-of-life/patient-reported outcomes central to treatment selection.
We recently, with Andrew Hahn, MD, and Nizar M. Tannir, MD, FACP, of MD Anderson Cancer Center, published a phase 2 study [NCT05012371] looking at lenvatinib plus everolimus in comparison with cabozantinib, showing that the combination is not inferior to cabozantinib and was actually showing a trend to better PFS. [LITESPARK-011] is a larger, phase 3, randomized study, using lenvatinib plus belzutifan, and the study has met its primary end point of PFS, [which could be] practice-changing. It remains to see how big of a PFS benefit it will have.
We would also look forward to seeing the patient-reported outcome data when you’re using a combination of 2 therapies vs cabozantinib alone. How did that look? Does the patient have improvement in that reported outcome by having the disease being controlled longer, or did they have deterioration because of the cumulative adverse effects of a VEGF TKI and a HIF-2α inhibitor? These nuances would be very interesting to see, and the OS data will also be reported. Those data are also interesting for us.
[It will also be worthwhile to investigate] the nuance of cost for a doublet using lenvatinib plus belzutifan vs maybe a doublet that is less expensive with everolimus. Those are studies to be had in the future.
Sonpavde: A recent press release reported that the phase 3 LITESPARK-011 trial showed improved PFS for belzutifan plus lenvatinib in patients with advanced RCC that had progressed on or after PD-1/L1 inhibitor therapy. Hence, results are eagerly anticipated.
Patient-reported outcomes in resected renal cell carcinoma: Active monitoring vs. durvalumab and tremelimumab in the RAMPART trial.
CYTOSHRINK: A randomized phase II trial of cytoreductive stereotactic hypofractionated radiotherapy with ipilimumab/nivolumab for metastatic kidney cancer.
Merseburger: RAMPART and CYTOSHRINK explore perioperative and cytoreductive strategies in the modern immunotherapy era. These readouts may help clarify where belzutifan-based regimens fit relative to established VEGF TKI/PD-(L)1 paradigms, and how patient-reported outcomes and tolerability should be weighed alongside efficacy. Together, these studies may further refine patient selection for the timing of systemic therapy and combination approaches.
References
- Merck announces KEYTRUDA® (pembrolizumab) plus WELIREG® (belzutifan) met primary endpoint of disease-free survival (DFS) in certain patients with clear cell renal cell carcinoma (RCC) following nephrectomy. Merk. News Release. October 28, 2025. Accessed February 9, 2026. https://www.merck.com/news/merck-announces-keytruda-pembrolizumab-plus-welireg-belzutifan-met-primary-endpoint-of-disease-free-survival-dfs-in-certain-patients-with-clear-cell-renal-cell-carcinoma-rcc-follow/
- Merck & Co., Inc., Rahway, NJ, USA and Eisai announce WELIREG® (belzutifan) plus LENVIMA® (lenvatinib) met primary endpoint of progression-free survival (PFS) in certain previously treated patients with advanced renal cell carcinoma. Eisai Global. News Release. October 28, 2025. Accessed February 9, 2026. https://www.eisai.com/news/2025/news202575.html
