Background
Phase III RCT (N=816) of resected clear-cell RCC at high recurrence risk after radical or partial nephrectomy with negative margins (T2a G3-4, T2b, T3, T4 any grade N0M0, or any T N1M0), no residual or distant disease; randomized 4-12 weeks post-nephrectomy.
Interventions and follow up
Arm A: Nivolumab 240mg IV q2wk x12 PLUS ipilimumab 1mg/kg IV q6wk x4
Arm B: Placebo
Primary endpoint: DFS by blinded independent central review
Median follow-up: 37mo
Arm B: Placebo
Primary endpoint: DFS by blinded independent central review
Median follow-up: 37mo
Results
mDFS (A vs B): not reached vs 50.7mo; HR 0.92, 95% CI 0.71-1.19, P=.53
OS: immature; only 61 deaths (33 in arm A, 28 in arm B), interim OS analysis not triggered
OS: immature; only 61 deaths (33 in arm A, 28 in arm B), interim OS analysis not triggered
Adverse events
Grade 3-5 AEs (A vs B): 38% vs 10%
Discontinuation due to AEs (A vs B): 32% vs 2%; treatment-related deaths reported in arm A
Discontinuation due to AEs (A vs B): 32% vs 2%; treatment-related deaths reported in arm A
Conclusions
Adjuvant nivolumab plus ipilimumab did not improve DFS versus placebo in resected high-risk clear-cell RCC.
Key Limitations
Negative primary endpoint despite an active dual-checkpoint regimen; high toxicity and discontinuation limited dose delivery; OS immature.
Clinical Context
Negative adjuvant immunotherapy trial contrasting with the positive KEYNOTE-564 pembrolizumab result, underscoring that adjuvant PD-1 monotherapy (pembrolizumab) remains the only approved adjuvant immunotherapy in RCC per ASCO/ESMO. Nivolumab/ipilimumab is not used adjuvantly.