Durvalumab and Tremelimumab After Surgery for High-Risk Kidney Cancer
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RAMPART: Does Durvalumab ± Tremelimumab After Kidney Cancer Surgery Reduce Recurrence Risk?
Study design
RAMPART is an international, randomized, multi-arm phase 3 study in patients whose primary renal cell cancer had been completely removed and whose recurrence risk was considered intermediate-high or high. It included patients with intermediate or high recurrence risk by Leibovich score and M1 NED patients whose limited metastatic disease had been completely resected.
| Treatment arm | Number of patients | Treatment | Clinical aim |
|---|---|---|---|
| Active monitoring | 340 | Scheduled follow-up, no adjuvant immunotherapy | Standard monitoring arm. |
| Durvalumab monotherapy | 225 | Durvalumab 1500 mg, every 4 weeks, for 1 year | To test whether single-agent PD-L1 blockade reduces recurrence. |
| Durvalumab + tremelimumab | 225 | Durvalumab for 1 year + tremelimumab 75 mg on day 1 and week 4 | To test the additional benefit of dual PD-L1 + CTLA-4 checkpoint blockade. |
It is immune treatment given after surgery removes the visible tumor, to suppress cancer cells that may remain microscopically and reduce recurrence risk.
Main efficacy results
Median follow-up was approximately 3,5 years . Durvalumab + tremelimumab significantly improved DFS compared with active monitoring: 3-year DFS was 80% vs 72%, HR 0,65. By contrast, durvalumab monotherapy increased 3-year DFS to 78% vs 72% , but did not meet the prespecified statistical significance threshold.
| Outcome | Durvalumab + tremelimumab | Durvalumab monotherapy | Active monitoring | Interpretation |
|---|---|---|---|---|
| 3-year DFS | %80 | %78 | %72 | Combination positive; monotherapy did not cross the statistical threshold. |
| DFS HR | 0,65 | 0,74 | Reference | Risk reduction was more pronounced with the combination. |
| 3-year OS | %96 | %98 | %96 | No significant difference in overall survival yet. |
| OS HR | 0,71 | 0,99 | Reference | OS data are immature and show no difference. |
The strongest signal is in high-risk patients
RAMPART’s most clinically meaningful finding is that benefit becomes particularly apparent in higher-risk patients. In those with high Leibovich risk or M1 NED, 3-year DFS with durvalumab + tremelimumab was %76, compared with %61 under active monitoring. HR was reported as 0,52 . Durvalumab monotherapy did not show a significant benefit in this high-risk group.
The picture is different in intermediate-risk patients
No clear DFS benefit from the combination was observed in patients with intermediate Leibovich risk. The 3-year DFS rates for durvalumab + tremelimumab, durvalumab, and active monitoring were 86%, 92%, and 85% , respectively. RAMPART should therefore not be interpreted as “dual immunotherapy for all adjuvant RCC patients.”
Safety and quality of life
Toxicity increased markedly with dual immunotherapy. Grade 3–4 adverse effects were reported at approximately %41in the combination arm, compared with %30 with durvalumab monotherapy. Treatment discontinuation and steroid use were also noteworthy in the combination arm. Rare but serious fatal immune-related adverse effects, particularly myasthenia gravis and myocarditis, were also reported.
Durvalumab is an immunotherapy targeting the PD-L1 pathway. Tremelimumab targets the CTLA-4 pathway. Removing two different immune brakes together may produce a stronger antitumor response, but may also increase immune-related adverse effects.
How does it relate to KEYNOTE-564?
The strongest established adjuvant RCC evidence today is the DFS and OS benefit of adjuvant pembrolizumab from KEYNOTE-564, particularly in clear-cell RCC. RAMPART should therefore not be read as directly “replacing pembrolizumab.” Its control arm was active monitoring; there was no head-to-head comparison with pembrolizumab.
Critical reading: How should RAMPART be interpreted in a balanced way?
- Durvalumab monotherapy was negative: Despite the numerical DFS difference, the prespecified statistical threshold was not met.
- The combination was positive, but toxic: Durvalumab + tremelimumab improved DFS; however, grade 3–4 adverse effects, steroid requirements, and rare fatal immune toxicities are important.
- Benefit is concentrated in high risk: There was no clear DFS benefit for the combination in intermediate-risk patients. Patient selection will be decisive.
- OS is not yet different: 3-year OS rates in all three arms were around 96–98%, with no significant difference.
- No direct comparison with pembrolizumab: After KEYNOTE-564, the role of RAMPART should be considered particularly in high-risk patients whose suitability for pembrolizumab is debatable.
- Study circumstances matter: The impact of the KEYNOTE-564 results and the COVID-19 period on study conduct should be taken into account in interpretation.
Message for clinical practice
RAMPART is one of the first large positive signals showing that dual checkpoint blockade may reduce recurrence risk in adjuvant RCC. However, the most rational setting today may not be all intermediate-high-risk patients, but those with the highest recurrence risk, such as high Leibovich risk or M1 NED patients.
How should this be explained to the patient?
“After kidney cancer is completely removed surgically, the disease can return in some patients. In RAMPART, giving two immunotherapies together reduced recurrence risk, particularly in high-risk patients. However, this treatment can have serious immune-related adverse effects, and it has not yet been shown to extend life. The decision should therefore consider your recurrence risk together with your likelihood of tolerating adverse effects.”
Drozdogan Academic Commentary
RAMPART adds important evidence to immunotherapy in adjuvant kidney cancer, but requires careful interpretation. Durvalumab monotherapy’s failure to cross the prespecified statistical success threshold suggests that single-agent PD-L1 blockade does not appear strong enough to replace adjuvant pembrolizumab in this setting.
Conversely, the DFS benefit seen with durvalumab + tremelimumab, particularly in high-risk patients, indicates that dual checkpoint blockade may be biologically meaningful. Yet pembrolizumab remains the historical reference in adjuvant RCC today, because KEYNOTE-564 demonstrated not only DFS but also an overall survival advantage.
RAMPART should therefore be read not as a “new standard replacing pembrolizumab,” but as a study opening the door to more intensive immunotherapy strategies in selected patients at very high recurrence risk. The right question in adjuvant treatment should no longer be only “Can we reduce recurrence?”, but “In which patient, at what toxicity cost, and with a genuine effect on length of life can we achieve this benefit?”
Conclusion
In RAMPART, durvalumab monotherapy numerically improved DFS versus active monitoring after RCC resection, but did not meet the prespecified significance threshold. Durvalumab + tremelimumab improved 3-year DFS to 80% versus 72%, with HR 0,65 and a statistically positive result.
The strongest benefit occurred in high-risk patients: 3-year DFS 76% versus 61%, HR 0,52. However, OS is not yet different, and dual-immunotherapy toxicity is substantial. RAMPART should therefore be viewed as important evidence for treatment intensification in adjuvant RCC that merits discussion in carefully selected patient groups.
- ASCO 2026 LBA4511. Durvalumab monotherapy versus active monitoring for resected primary RCC in RAMPART.
- ASCO Daily News. RAMPART: Adjuvant durvalumab does not improve DFS in intermediate-/high-risk RCC.
- OncLive. Adjuvant Durvalumab Plus Tremelimumab Shows DFS Advantage Over Active Monitoring in Resected RCC. 2026.
- OncoDaily. RAMPART at ASCO 2026: durvalumab monotherapy vs active monitoring in resected RCC.
- UroToday. ASCO 2026: RAMPART durvalumab monotherapy and combination results.
- UroToday. ESMO 2025: First results from RAMPART durvalumab + tremelimumab.
- Choueiri TK et al. Overall Survival with Adjuvant Pembrolizumab in Renal-Cell Carcinoma. New England Journal of Medicine. 2024.
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