In resected RCC, durvalumab/tremelimumab combo bests monotherapy on DFS

Durvalumab (Imfinzi) monotherapy did not achieve a statistically significant improvement in disease-free survival (DFS) compared with active monitoring following resection of primary renal cell carcinoma (RCC), according to updated data from the phase 3 RAMPART trial (NCT03288532) presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

The updated durvalumab monotherapy results, presented by James M.G. Larkin, MD, PhD, of the Royal Marsden NHS Foundation Trust, London, UK, follow the combination arm data presented at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, Germany. These results demonstrated a statistically significant DFS benefit for durvalumab plus tremelimumab (Imjudo) over active monitoring.

Related: Adjuvant durvalumab plus tremelimumab after RCC resection improves DFS

Trial design and population

RAMPART is an international, investigator-led, multi-arm, multi-stage platform trial conducted at 80 sites across the United Kingdom, Spain, France, and Australia. The investigators enrolled a total of 790 patients with confirmed RCC at intermediate or high risk of relapse, defined by a Leibovich score of 3 to 5 (intermediate) or 6 or higher (high), as well as those with fully resected synchronous ipsilateral adrenal metastases or a single resected soft tissue metastasis (M1 NED). Patients were randomly assigned in a 3:2:2 ratio to active monitoring (n = 340), durvalumab 1500 mg every 4 weeks for 1 year (n = 225), or durvalumab plus tremelimumab 75 mg at day 1 and week 4 for 1 year (n = 225).

Recruitment was impacted by the COVID-19 pandemic and the reporting of the KEYNOTE-564 (NCT03142334) trial, which led to FDA approval of adjuvant pembrolizumab in November 2021. The statistical analysis plan was adjusted prior to any unblinded data review, with 80% power maintained across primary comparisons, and a prespecified and pre-powered subgroup analysis of DFS stratified by risk of relapse at baseline was retained.

Baseline characteristics were well-balanced across arms. The median age was approximately 59 to 60 years, roughly 70% of participants were male, and clear cell histology represented about 84% of the enrolled population. Pathological T3 disease was present in the majority of participants across all arms (72% to 75%), and approximately 5% of patients were classified as M1 NED.

Efficacy: Durvalumab monotherapy vs active monitoring

In the intention-to-treat (ITT) population analyzed at a median follow-up of 3.5 years, durvalumab monotherapy was associated with a 26% relative reduction in the hazard of disease recurrence or death vs active monitoring, although the difference was not statistically significant (HR, 0.74; 95% CI, 0.53 to 1.04; one-sided P = .041). The 3-year DFS rates were 78% and 72%, respectively.

In the prespecified, pre-powered subgroup analysis of patients classified as higher-risk (those with high Leibovich score or M1 NED), the HR for durvalumab monotherapy was 0.77 (95% CI, 0.53 to 1.12; one-sided P = .085) vs active monitoring. The 3-year DFS rates in this subgroup were 66% for durvalumab monotherapy and 61% for active monitoring.

In intermediate-risk patients, the curves converged nearly completely, with 3-year DFS exceeding 85% in all arms. Compared with active monitoring, the HR for durvalumab monotherapy was 0.64 (95% CI, 0.30 to 1.34; one-sided P = .12).

The interaction P-value for higher- vs intermediate-risk in the durvalumab monotherapy arm was 0.663, indicating no statistically significant differential effect by risk group. This is in contrast with the combination arm, where the interaction P-value was 0.019, suggesting a more pronounced benefit concentrated among higher-risk patients.

Efficacy: Durvalumab plus tremelimumab vs active monitoring

The combination arm results, initially reported at ESMO 2025 and confirmed in the integrated ASCO 2026 presentation, demonstrated a statistically significant DFS benefit with the combination. In the ITT population, the combination produced an HR of 0.65 (95% CI, 0.45 to 0.93; one-sided P = .0094) vs active monitoring, with 3-year DFS rates of 80% and 72%, respectively.

In the higher-risk subgroup, the DFS benefit was more pronounced, with an HR of 0.52 (95% CI, 0.34 to 0.80; one-sided P = .0016) and 3-year DFS of 76% vs 61%. In intermediate-risk patients, the HR was 1.19 (95% CI, 0.61 to 2.32; P = .309), with 3-year DFS rates of 86% vs 85%.

Overall survival data remain immature. Three-year OS rates exceeded 96% in all 3 arms, with HRs for both treatment comparisons that were not statistically significant at this analysis.

Safety

Immune-mediated toxicity was consistent with the known profiles of PD-L1 and CTLA-4 inhibitors, though rare and serious events were observed in both treatment arms. Grade 3 or 4 adverse events (AEs) of any cause occurred in 41% of combination-arm participants and 30% of durvalumab monotherapy participants, compared with 9% in the active monitoring arm. Treatment discontinuation due to AEs occurred in 29% and 19% of patients in the combination and monotherapy arms, respectively.

Two treatment-related deaths were attributed to the combination regimen, both due to immune-mediated myasthenia gravis, and 1 treatment-related death occurred in the durvalumab monotherapy arm, attributed to myocarditis.

Corticosteroid use was required in 43% of participants receiving the combination and 23% of those receiving durvalumab monotherapy. The most common high-grade AEs in the combination arm were diarrhea/colitis (11%), elevated amylase/lipase (6%), and transaminitis (6%). No statistically significant or clinically meaningful difference in quality of life, measured as change in overall health from baseline to month 15, was observed in either treatment arm vs active monitoring.

REFERENCE

1. Larkin J, Powles T, Frangou E, et al. Durvalumab monotherapy versus active monitoring for resected primary renal cell carcinoma in RAMPART: An international, phase 3, randomized controlled trial. J Clin Oncol. 44, 2026 (suppl 17; abstr LBA4511). doi:10.1200/JCO.2026.44.17_suppl.LBA4511