Pembrolizumab (PD-1) + high-dose IL-2 (T-cell–activating cytokine) drives 42% CRs and >84-mo OS in 1L ccRCC

Pembrolizumab (anti–PD-1) combined with high-dose interleukin-2 (aldesleukin; pleiotropic T-cell/NK-cell activating cytokine) was evaluated as a fixed-duration, single-arm Phase 2 regimen in treatment-naive advanced clear cell RCC (NCT02964078). With 76.4 months median follow-up, 26 treated patients had ORR 73% with 42% complete responses; median PFS was 19.3 months, median OS was >84 months, and median treatment-free interval was 23.8 months, with 42% treatment-free at 5 years. No grade 5 AEs were reported; notably, patients with durable disease control did not have persistent grade ≥2 toxicities—an “off-therapy” upside compared with current 1L IO/TKI or IO/IO approaches that typically yield ORR ~42–71% and CR ~9–16% with median PFS ~12–24 months in large Phase 3 trials (cross-trial comparison, acknowledging different case-mix).