Clinical Summary:

• Design/Population: In the phase 3 RAMPART trial, patients with intermediate- or high-risk renal cell carcinoma following nephrectomy or complete resection of limited metastatic disease were randomized to receive active monitoring, durvalumab monotherapy, or durvalumab plus tremelimumab.
• Key Outcomes: Durvalumab monotherapy reduced the risk of recurrence or death compared with active monitoring but did not achieve the prespecified threshold for statistical significance for disease-free survival. 
• Clinical Relevance: These findings suggest that dual checkpoint blockade may be required to achieve meaningful disease-free survival improvement in the adjuvant treatment of higher-risk renal cell carcinoma.

Results from the phase 3 RAMPART trial demonstrated that adjuvant durvalumab monotherapy did not significantly improve disease-free survival (DFS) compared with active monitoring among patients with intermediate- or high-risk renal cell carcinoma who underwent complete resection of limited metastatic disease. 

These results were presented by James Larkin, MD, PhD, The Royal Marsden NHS Foundation Trust, London, United Kingdom, at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

In this study, 790 patients who underwent nephrectomy or complete resection of limited metastatic disease were randomized 3:2:2 to receive active monitoring (n = 340), 1500 mg of durvalumab once every 4 weeks for 13 cycles (n = 225), or 1500 mg of durvalumab once every 4 weeks plus 75 mg of tremelimumab during cycles 1 and 2 only (n = 225). The primary end point was DFS. 

At analysis, durvalumab monotherapy was associated with a 26% relative reduction in the risk of disease recurrence or death compared with active monitoring, however statistical significance was not reached (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.53 to 1.04; P = .041). DFS at 3 years was 78% in the durvalumab arm and 72% in the active monitoring arm. 

In a prespecified analysis according to risk of recurrence, there was no evidence of a treatment-by-subgroup interaction. The findings differed from the previously reported primary analysis comparing durvalumab plus tremelimumab with active monitoring, which demonstrated a statistically significant improvement in DFS. 

As Dr Larkin concluded, “durvalumab plus tremelimumab was associated with a statistically significant improvement in DFS, which was not observed with durvalumab monotherapy.” 

Source:

Larkin JMG, 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. Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. LBA4511.