Multicenter phase 2 trial of adjuvant penpulimab in very-high risk clear cell renal cell carcinoma

Patients with very-high risk clear cell renal cell carcinoma (ccRCC) remain at substantial risk of recurrence after nephrectomy. A multicenter phase 2 trial in China evaluated adjuvant penpulimab (anti-PD-1) for very-high risk ccRCC patients after nephrectomy. Patients received either adjuvant penpulimab or routine surveillance, with 1:1 propensity score matching applied to balance baseline characteristics, yielding well-balanced cohort of 87 patients per group. The primary endpoint was disease-free survival (DFS). Adjuvant penpulimab was associated with improved DFS compared with surveillance (HR 0.37; p=0.026), whereas overall survival data were immature. Penpulimab was generally well tolerated, with most treatment-related adverse events being grade 1 or 2. Plasma proteomic and metabolomic analyses revealed enrichment of immune response-related pathways in patients without disease progression. The authors conclude that adjuvant penpulimab was associated with improved DFS and manageable safety in patients with very-high risk ccRCC.