Decoding RAMPART: Durvalumab Monotherapy Vs Combination Therapy in RCC

The optimal role of adjuvant immunotherapy for patients with resected renal cell carcinoma (RCC) remains one of the most actively debated topics in genitourinary oncology. In an interview with CancerNetwork® at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, Saum Ghodoussipour, MD, provided a comprehensive breakdown of the newly updated results from the international phase 3 RAMPART trial (NCT03288532).¹

Ghodoussipour first contextualized how these new findings build upon previously reported data, drawing a sharp contrast between the treatment arms. While a combination of the PD-L1 inhibitor durvalumab (Imfinzi) and the CTLA-4 inhibitor tremelimumab (Imjudo) demonstrated a statistically significant disease-free survival (DFS) benefit in a readout at the European Society for Medical Oncology Congress 2025, predominantly driven by the high-risk patient population, the newly unveiled durvalumab monotherapy data failed to reach statistical significance.²

Ghodoussipour further analyzed these surprising monotherapy outcomes, particularly in light of established historical benchmarks like pembrolizumab (Keytruda), offering critical insights into what these disparate hazard ratios (HRs) could mean for risk stratification and clinical practice.

Ghodoussipour is the director of the Bladder and Urothelial Cancer Program at Rutgers Cancer Institute and an associate professor of Surgery at Rutgers Robert Wood Johnson Medical School.

CancerNetwork: What were some of the key efficacy findings of the RAMPART Trial?

Ghodoussipour: This year at ASCO, they updated a presentation that was given at last year’s ESMO. Last year at ESMO, they focused on the outcomes of patients in the combination group vs active monitoring. This year at ASCO, they updated the results to show the outcomes in the durvalumab monotherapy group. Putting it all together, last year at ESMO, they showed that the combination of durvalumab plus tremelimumab led to a [DFS] benefit compared with active monitoring alone. That [DFS rate] was 81% vs 73% in those patients, with [an HR] of 0.65 that was statistically significant across the 2 groups. However, when they stratified that [HR] by intermediate- vs high-risk disease according to the Leibovich criteria, pretty much all the benefit seemed to come from the patients in the high-risk group. Their [HR] was 0.52, and then the intermediate-risk population had a non-significant [HR] of 1.19.

This year, they presented the durvalumab data. Looking at the entire cohort, it was 790 patients––a bit over 200 in each of the therapy groups, and almost [approximately] 340 in the active monitoring group. They saw that the 3-year DFS [rate] was 80% with the combination, 78% with durvalumab [monotherapy], and 72% with active monitoring. There was not a benefit in terms of [DFS] with durvalumab monotherapy. The [HR] there was 0.74, but the confidence interval went from [0.53] and crossed 1, so it was not statistically significant in the group overall. It was also not significant in the high-risk population.

The overall conclusion is that the combination of durvalumab plus tremelimumab [has] a [DFS] benefit that seems to be concentrated in those at a high risk of recurrence. However, for the monotherapy—it was surprising to some because of the data we have with pembrolizumab—there was no benefit in that regard.

References

1. Larkin JM, 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. 2026;44(suppl 17):LBA4511. doi:10.1200/JCO.2026.44.17_suppl.LBA4511
2. Larkin JM, Powles T, 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. Ann Oncol. 2025;36(suppl 2):S1635. doi:10.1016/j.annonc.2025.09.110