RAMPART is a randomised trial of immune checkpoint inhibitor therapy for 1 year versus active monitoring after resection of primary renal cell carcinoma.
We recruited participants (pts) from 80 sites and randomised them in a 3:2:2 ratio between: Arm A, active monitoring; Arm B, 1 year (13 cycles) of durvalumab; or Arm C, 1 year (13 cycles) of durvalumab plus tremelimumab (cycles 1 and 2 only). Recruitment was stopped early for reasons other than efficacy or safety, and the statistical analysis plan was adjusted before any unblinded analyses. The modified plan gives 80% power to detect a true hazard ratio (HR) for disease free survival (DFS) of 0.55 for Arms C vs. A, and 0.60 for Arms B vs. A, with an overall, familywise, 1-sided type I error rate strongly controlled at 2.5% across all primary analyses. Here we present results of Arms C vs A. All p-values are 1-sided; 95% confidence intervals are 2-sided.
Between October 2018 and June 2023, we randomised 790 pts: 340 Arm A, 225 Arm B, 225 Arm C. Baseline characteristics were similar in Arms C and A: median age (range) was 60 (22, 83) years, 70% were male, and 84% had clear cell histology. DFS was longer among those assigned durvalumab and tremelimumab (Arm C) than active monitoring (Arm A); DFS at 2 years 84% vs. 78%, HR 0.65, 95% CI 0.45 to 0.93, 1p=0.0094. Pre-specified and pre-powered DFS analysis in 311 higher-risk pts (Table) showed a HR= 0.52, 95% CI 0.34 to 0.80, 1p=0.0016 (2 year DFS Arm C 81% vs Arm A 67%), interaction HR 0.43, 95% CI 0.19, 0.95, 1p for testing whether the interaction equals 1=0.019; HR in intermediate risk pts was 1.19, 95% CI 0.61 to 2.32, 1p=0.309. No unexpected safety signals were observed. Results of Arms B vs A are expected in next 12 months.
| A | C | Total | |
| N=340 | N=225 | N=565 | |
| Leibovich Intermediate Risk | 151 (44%) | 103 (46%) | 254 (45%) |
| Leibovich High Risk | 172 (51%) | 111 (49%) | 283 (50%) |
| M1NED | 17 (5%) | 11 (5%) | 28 (5%) |
Adjuvant therapy with durvalumab and tremelimumab after resection of RCC improved DFS, particularly among those at highest risk of relapse.
NCT03288532; ISRCTN53348826; EudraCT: 2017-002329-39.