RAMPART Trial Does Not Meet DFS End Point in RCC

The primary end point of diease-free survival (DFS) was not met in the phase 3 RAMPART (NCT03288532) trial, which assessed durvalumab (Imfinzi) monotherapy vs standard-of-care active monitoring for patients with resected renal cell carcinoma (RCC) who had intermediate or high-risk of recurrence.

The findings, shared at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, detailed a 26% relative reduction in the risk of disease recurrence or death with durvalumab monotherapy (HR, 0.74; 95% CI, 0.53-1.04; 1-sided P =.041); however, the figure did not cross the prespecified threshold for statistical significance. The 3-year DFS rate was 78% with durvalumab vs 72% with active monitoring, amounting to an absolute difference of 6 percentage points.

By contrast, in initial data from RAMPART reported at the 2025 European Society for Medical Oncology (ESMO) Congress, the combination of durvalumab plus tremelimumab (Imjudo) achieved a statistically significant DFS improvement, an effect driven largely by patients in the higher-risk subgroups, such as those with a high Leibovich Score or M1 with no evidence of disease (M1NED) following complete resection.² The hazard ratio (HR) for the combination arm was 0.65 vs active monitoring.

These data, reported from 790 randomized patients across 80 sites in 4 countries, add important nuance to the adjuvant immunotherapy landscape for RCC, a setting in which only pembrolizumab (Keytruda) has received regulatory approval to date.

“The key message is that durvalumab monotherapy following resection of renal cell carcinoma showed no statistically significant improvement in disease-free survival compared with active monitoring,” said James M.G. Larkin, MD, PhD, FRCP, of The Royal Marsden NHS Foundation Trust, during the presentation.¹

RAMPART Trial Design and Population

RAMPART enrolled 790 patients from 80 sites across the United Kingdom, France, Australia, and Spain between October 2018 and June 2023.³ Patients were randomized 3:2:2 to active monitoring (arm A; n = 340), durvalumab 1500 mg for 13 cycles over 1 year (arm B; n = 225), or durvalumab 1500 mg plus tremelimumab 75 mg in cycles 1 and 2 only (arm C; n = 225). Median age was 60 years (range, 22–83); 72% of patients were male and 84% had clear cell histology. Baseline characteristics were balanced across arms.

The trial's original sample size target was 1150 patients, but recruitment was stopped earlier than planned following results of the KEYNOTE-564 (NCT03142334) trial, which established pembrolizumab as a treatment option for many patients who would have been RAMPART-eligible. The trial design was subsequently revised without knowledge of the accumulating RAMPART results.

The primary end point was DFS, with a prespecified and prepowered analysis of DFS by risk of relapse at baseline. Intermediate risk was defined as a Leibovich Score of 3 to 5, and high risk as a score of 6 or above.

Subgroup Analysis Findings

In the prespecified DFS analysis by risk of recurrence, no evidence of a treatment-by-subgroup interaction was observed for the durvalumab monotherapy vs active monitoring comparison. In the higher-risk subgroup, which included patients with high Leibovich scores and those with M1NED disease, the HR for durvalumab monotherapy vs active monitoring was 0.77 (95% CI, 0.53-1.12; 1-sided P =.085), which was not statistically significant. In the intermediate-risk group, 3-year DFS rates across all arms exceeded 85%, and neither experimental arm resulted in a statistically significant difference vs active monitoring.

This contrasts with the combination arm results, where the DFS benefit of durvalumab plus tremelimumab was concentrated in higher-risk patients. Here, the HR was 0.52, which reached statistical significance.

Safety Findings

Safety findings were consistent with the known profiles of these agents. However, rare and serious immune-mediated adverse events were observed, including 2 fatal myasthenia gravis events and 1 fatal myocarditis event. There were 2 treatment-related deaths in the durvalumab plus tremelimumab arm and 1 in the durvalumab monotherapy arm. Adverse events leading to treatment discontinuation occurred in 19% of patients receiving durvalumab monotherapy vs 29% in the combination arm. Corticosteroid use was required in 23% of patients in the durvalumab monotherapy arm and 43% in the combination arm.

The most common severe adverse events in the trial were diarrhea and colitis, amylase and lipase elevation, and transaminitis. Across all adverse event categories, the combination arm was associated with higher rates of events than durvalumab monotherapy or active monitoring. In terms of treatment exposure, 32% of patients receiving durvalumab monotherapy completed treatment per protocol, with a median of 11 infusions out of a maximum of 13; the corresponding completion rate in the combination arm was 23%.

DISCLOSURES: Larkin reported receipt of honoraria from Bristol-Myers Squibb, Cancer Research UK, Eisai, GlaxoSmithKline, Gynavax, Incyte, iOnctura, Merck Serono, Novartis, Pfizer, Roche, touchEXPERTS, touchIME; a consulting or advisory role with Apple Tree Partners, Boston Biomedical, Bristol-Myers Squibb, Eisai, Immunocore, Incyte, iOnctura, Iovance Biotherapeutics, Merck Serono, MSD Oncology, Novartis, Pfizer, YKT Corporation; and receipt of institutional research funding from Achilles Therapeutics, AVEO, Bristol-Myers Squibb, Covance, Immunocore, MSD, Nektar, Novartis, Pfizer, Pharmacyclics, and Roche.

References

1. Larkin, JMG. Durvalumab monotherapy versus active monitoring for resected primary renal cell carcinoma in RAMPART: An international, phase 3, randomized controlled trial. Presented at: ASCO Annual Meeting; May 29–June 2, 2026; Chicago Illinois. Abstract LBA4511.

2. Larkin J, Powles TB, Frangou E, et al. LBA93 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. Ann Oncol. 2025;36:S1635. doi:10.1016/j.annonc.2025.09.110

3. Renal Adjuvant MultiPle Arm Randomised Trial (RAMPART). ClinicalTrials.gov. Updated September 7, 2020. Accessed May 30, 2026. https://clinicaltrials.gov/study/NCT03288532

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