Adjuvant durvalumab plus tremelimumab after RCC resection improves DFS

Initial results from the phase 3 RAMPART trial (NCT03288532) show that adjuvant durvalumab (Imfinzi) plus tremelimumab (Imjudo) following resection of primary renal cell carcinoma (RCC) improved disease-free survival (DFS) vs active monitoring.¹

The findings, presented at the 2025 European Society for Medical Oncology Congress in Berlin, Germany by James Larkin, PhD, FRCP, indicate that the DFS improvement was largely driven by the treatment effect in patients at higher risk of relapse.

“In a subgroup of patients facing a high risk of cancer returning after surgery, we saw a remarkable result, with over a 43% relative reduction in the risk of recurrence,” Larkin explained in a news release on the data.² “These are very promising findings that confirm the benefit of immunotherapy in the treatment of high-risk renal cell carcinoma.”

The study enrolled patients in a 3:2:2 fashion across 3 treatment arms: active monitoring (arm A; n = 340), durvalumab 1500 mg Q4W for 1 year (arm B; 225), and durvalumab 1500 mg Q4W for 1 year plus tremelimumab 75 mg at day 1 and week 4 (arm C; n = 225). The primary end point was DFS.

The data reported at ESMO included a comparison between arm C (durvalumab plus tremelimumab) vs arm A (active monitoring). Baseline characteristics were well-balanced between treatment groups. The primary analysis in the study had an 80% power to detect an effect, with a 1-sided significance level of 0.0129.

At the landmark 3-year analysis in the intent-to-treat population, data showed a DFS of 81% in the durvalumab plus tremelimumab arm vs 73% in the active monitoring arm (HR, 0.65; 95% CI, 0.45 to 0.93; 1-sided P = .0094). When assessing DFS by risk group, the 3-year DFS in patients at higher risk of relapse was 78% in the durvalumab plus tremelimumab arm (n = 122) vs 61% in the active monitoring arm (n = 189) (HR, 0.52; 95% CI, 0.34 to 0.80; 1-sided P = .0016). In the intermediate risk population, 3-year DFS was 86% in the durvalumab plus tremelimumab arm (n = 103) vs 87% in the active monitoring arm (n = 151), which did not achieve statistical significance (HR, 1.19; 95% CI, 0.61 to 2.32; 1-sided P = .309).

The test for interaction “provid[ed] good evidence of an interaction between risk of relapse and disease-free survival,” according to Larkin, with a HR of 0.43 (95% CI, 0.19 to 0.95; P = .019).

DFS favored the treatment arm over the control arm across all exploratory subgroups.

The median duration of treatment was 10.9 months (range, 0 to 13.3 months). Overall, 23% of patients completed treatment per protocol, with 24% of patients receiving 13 durvalumab infusions and 73% receiving both tremelimumab infusions.

The rate of any-grade adverse events (AEs) was 97% in the treatment arm and 63% in the control arm. Grade 3 or higher AEs were reported in 40% of patients in the durvalumab plus tremelimumab arm and 8% of patients in the active monitoring arm.

Larkin also noted, “There were 15 deaths in the active monitoring arm and 9 in the durva/treme arm, noting that there were 6 myocarditis [serious] AEs in 4 patients, 2 of which unfortunately resulted in death.” According to Larkin, all-cause adverse events were in-line with what is expected for this combination of checkpoint inhibitors.

Quality of life data showed no statistically significant difference between the 2 arms in terms of change in overall health and quality of life from baseline to 15 months (mean difference, 1.0; 95% CI, -4.6 to 6.5; P = .7324).

Larkin added, “The results of the durvalumab vs active monitoring comparison, that's arm B vs arm A, are expected in 2026 depending on how quickly rates accrue.”

DISCLOSURES: Larkin noted financial and consulting disclosures with Roche, Novartis, iOnctura, BMS, Pfizer, Incyte, Dynavax, CRUK, GSK, Eisai, Merck touchIME, touchEXPERTs, Iovance, Boston Biomedical, Immunocore, YKT Global, Apple Tree, Roche, Pierre Fabre, AstraZeneca, EUSA Pharma, MSD, Ervaxx, Ipsen, Aptitude, Calithera, Ultimovacs, Seagen, Achilles Therapeutics, Nektar Therapeutics, Covance, Immunocore, Pharmacyclics, and Aveo.

REFERENCES

1. Larkin J, Powles TB, Frangou E, et al. First results from RAMPART: An international phase III randomised-controlled trial of adjuvant durvalumab monotherapy or combined with tremelimumab for resected primary renal cell carcinoma (RCC) led by MRC CTU at UCL. Presented at: 2025 European Society for Medical Oncology Congress. October 17-21, 2025. Berlin, Germany. LBA93

2. International trial shows combination immunotherapy treatment significantly improves survival in high-risk kidney cancer patients. News release. The Royal Marsden NHS Foundation Trust. October 18, 2025. Accessed October 22, 2025. https://www.royalmarsden.nhs.uk/news-and-events/news/RAMPART-trial