(UroToday.com) The 2025 European Society of Medical Oncology (ESMO) Annual Congress held in Berlin, Germany, was host to the Poster Session. Dr. Qian Qin presented the poster EXPLORE-RCC: a phase II study of neoadjuvant zanzalintinib (ZANZA) plus nivolumab (NIVO) in patients with locally advanced and/or inoperable clear cell renal cell carcinoma (ccRCC).
Dr. Qin began by explaining that patients with locally advanced clear cell renal cell carcinoma (ccRCC) often have aggressive tumor biology, which can make surgical resection difficult. Neoadjuvant systemic therapy may help reduce tumor size, improve resectability, enable renal preservation by converting some cases from radical to partial nephrectomy, and allow for a minimally invasive approach. The EXPLORE-RCC trial was developed to evaluate neoadjuvant zanzalintinib (ZANZA) in combination with nivolumab in patients with locally advanced ccRCC.
The primary endpoint of the EXPLORE-RCC trial is objective response rate (ORR) at 12 weeks. Secondary endpoints include conversion from inoperable to operable disease, percentage tumor size decrease, and safety. Correlative and exploratory endpoints include overall survival in unresectable versus resectable patients, as well as changes in tumor thrombus level, pathologic complete response, tumor necrosis, and surgery-related outcomes such as the rate of radical versus partial nephrectomy and Clavien-Dindo complications. Additional analyses will assess disease-free survival, need for adjuvant therapy, and tumor microenvironment changes.
Key inclusion and exclusion criteria are summarized in the table below.
The EXPLORE-RCC trial is a multi-site, open-label, phase II study conducted at six centers across the United States (NCT06794229). Eligible patients included those with clear cell renal cell carcinoma, with or without sarcomatoid features, who had locally advanced and/or inoperable disease, an ECOG performance status of 0–1, and no comorbidities precluding systemic therapy. Participants received neoadjuvant zanzalintinib 60 mg orally once daily plus nivolumab every 2 or 4 weeks for 12 weeks.
Patients with stable or partial response who became operable proceeded to surgery, while those remaining inoperable continued therapy for up to 48 weeks or transitioned to standard-of-care treatment upon disease progression. Adjuvant therapy was permitted according to standard-of-care guidelines. The study design and schema is shown below.
This study was powered to detect an improvement in objective response rate (ORR) to 0.45 compared with a historical control rate of 0.3, with 80% power and a one-sided type I error of 0.05. Accounting for an anticipated 10% dropout rate, a total of 69 patients will be enrolled. Correlative analyses will include assessment of changes in circulating tumor cells, circulating tumor DNA, and biomarkers of immune activation and gene expression.
Lastly, Dr. Qin highlighted that this study represents a personalized, adaptive approach to neoadjuvant therapy using zanzalintinib in combination with nivolumab. This regimen has the potential to shrink locally advanced clear cell renal cell carcinoma, improving resectability and enabling more patients to undergo surgery with curative intent.
Presented by: Qian Qin, MD, Assistant Professor in the Department of Internal Medicine at UT Southwestern Medical Center, Dallas, United States of America.
Written by: Julian Chavarriaga, MD – Urologic Oncologist at Cancer Treatment and Research Center (CTIC) via Society of Urologic Oncology (SUO) Fellow at The University of Toronto. @chavarriagaj on Twitter during the 2025 European Society for Medical Oncology (ESMO) Annual Congress, Berlin, Germany, October 17–21, 2025