Pembrolizumab plus High-Dose IL-2 in Advanced Clear Cell Renal Cell Carcinoma: Six-Year Survival Outcomes and Molecular Signatures from a Phase 2 Trial
Discuss this preprint
Start a discussion What are Sciety discussions?Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Prolonged or indefinite systemic therapy remains standard for advanced clear cell renal cell carcinoma (ccRCC), often resulting in cumulative toxicities and treatment burden. We conducted a single-arm phase 2 trial of a fixed-duration regimen of pembrolizumab plus high-dose interleukin-2 in treatment-naive advanced ccRCC. Among 26 patients treated, after a median follow-up of 76.4 months, the objective response rate was 73%, with complete responses in 42%. Median overall survival was not reached, with 5-year survival of 73%; median progression-free survival was 19.3 months; and median treatment-free survival was 23.8 months, with 42% of patients remaining treatment-free at 5 years. No grade 5 adverse events occurred, and no patient with durable disease control experienced persistent grade ≥2 toxicities. Correlative analyses identified immune patterns associated with durable benefit, including enrichment of CD16⁺ natural killer cells, suppression of PD-1⁺ T-cell frequencies, and coordinated chemokine, complement, and PKC/TGF-β pathway activation. ClinicalTrials.gov identifier: NCT02964078.
