A phase II study assessing the feasibility and clinical efficacy of adaptive immunotherapy combination with VEGFR-TKI in patients with advanced renal cell carcinoma.

Kidney cancer is one of the 10 most common cancers affecting both men and women in the United States, accounting for 4% to 5% of all cancers. Most recent estimates have shown that about 81,610 new cases of kidney cancer will be diagnosed in 2024, with renal cell carcinoma (RCC). The treatment landscape of metastatic or unresectable locally advanced clear cell renal cell carcinoma (ccRCC) has changed over the past years with the approval of multiple combination regimens using immune checkpoint inhibitors (ICI) and vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI). However, this first‑line approach is associated with immense drug-related toxicity and financial burden. Recent research suggests that unlike traditional intermittent therapy, adaptive therapy modulates drug administration based on real-time tumor metrics to maintain a stable population of sensitive cells that suppress the growth of resistant clones. This phase II trial will assess the feasibility, patient acceptability, safety, and preliminary efficacy signals of a response-based multi-drug adaptive therapy approach with pembrolizumab-axitinib (pembro-axi) in patients with metastatic or unresectable locally advanced ccRCC.Clinical trial registration www.clinicaltrials.gov identifier is NCT06860386.