Adjuvant Durvalumab Plus Tremelimumab Shows DFS Advantage Over Active Monitoring in Resected RCC

Adjuvant durvalumab (Imfinzi) plus tremelimumab (Imjudo) significantly improved disease-free survival (DFS) compared with active monitoring in patients with resected high- or intermediate-risk renal cell carcinoma (RCC); however durvalumab monotherapy did not meet its pre-specified significance threshold for DFS, according to data from the phase 3 RAMPART trial (NCT03288532) presented during the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.¹

At a median follow-up of 3.5 years in the intention-to-treat population, durvalumab plus tremelimumab (n = 225) reduced the risk of disease recurrence or death by 35% vs active monitoring (n = 340; HR, 0.65; 95% CI, 0.45-0.93; 1-sided P = .0094). The 3-year DFS rates were 80% vs 72%, respectively. Durvalumab monotherapy (n = 225) yielded 3-year DFS rate of 78% vs 72% with active monitoring (HR, 0.74; 95% CI, 0.53-1.04; 1-sided P = .041)

Overall survival (OS) findings were comparable among the 3 arms, with no significant differences being reported between the combination (HR, 0.71; 95% CI, 0.34-1.46; 1-sided P = .176) or monotherapy (HR, 0.99; 95% CI, 0.52-1.92; 1-sided P = .492) compared with active monitoring. The 3-year OS rates were 96%, 98%, and 96%, respectively.

“The key messages are that durvalumab monotherapy, following resection of RCC, showed no statistically significant improvement in DFS compared with active monitoring,” James Larkin, PhD, FRCP, a professor and consultant medical oncologist at The Royal Marsden, NHS Foundation Trust, in London, England, said during the presentation. “[However], durvalumab plus tremelimumab significantly improved DFS compared with active monitoring. Safety findings were consistent with the known profiles of these agents, but rare immune-mediated adverse effects [AEs], including fatal [myasthenia] gravis and myocarditis, were observed.”

How was RAMPART designed?

RAMPART enrolled patients with confirmed RCC and high or intermediate Leibovich risk of relapse following radical or partial nephrectomy. Those with fully resected synchronous ipsilateral adrenal metastases or a single fully resected soft tissue metastasis were also included. The trial was originally designed to enroll 1750 patients but was scaled back following the impact of COVID-19 and the June 2021 FDA approval of adjuvant pembrolizumab (Keytruda) based on data from the phase 3 KEYNOTE-564 trial (NCT03142334).² 

Patients were randomly assigned 3:2:2 to durvalumab at 1500 mg every 4 weeks for 1 year plus tremelimumab at 75 mg at day 1 and week 4, durvalumab at 1500 mg every 4 weeks for 1 year, or active monitoring.¹

The primary end point was DFS, with 2 co–primary analyses using prespecified significance thresholds and staggered analysis timings. The durvalumab plus tremelimumab vs active monitoring comparison was analyzed on July 1, 2025 (threshold, 1-sided P = .0129), and the durvalumab vs active monitoring comparison was analyzed on February 23, 2026 (threshold, 1-sided P = .025).

At baseline, patients in the combination arm had a median age of 58.9 years (SD, 58.8). Most patients in this arm were male (72%), underwent radical nephrectomy (86%), had clear cell histology (85%), and had stage pT3 disease (72%).

In the active monitoring arm, the median age at baseline was 59.6 years (SD, 58.3). Most patients were male (71%), underwent radical nephrectomy (86%), had clear cell histology (84%), and had stage pT3 disease (75%).

What did the risk-stratified subgroup analyses show?

In a prespecified, pre-powered subgroup analysis of patients at higher risk of relapse, durvalumab plus tremelimumab (n = 122) demonstrated a pronounced DFS benefit vs active monitoring (n = 189; HR, 0.52; 95% CI, 0.34-0.80; 1-sided P = .0016), with 3-year DFS rates of 76% and 61%, respectively. In the intermediate-risk subgroup, no significant DFS benefit was observed with durvalumab plus tremelimumab vs active monitoring (HR, 1.19; 95% CI, 0.61-2.32; 1-sided P = .309)

For the durvalumab monotherapy (n = 102) vs active monitoring (n = 151) comparison in the intermediate-risk subgroup, the HR was 0.64 (95% CI, 0.30-1.34; 1-sided P = .12). The DFS HR for the combination arm (n = 103) vs active monitoring was 1.19 (95% CI, 0.61-2.32; 1-sided P = .309).

What did the safety analysis show?

In terms of safety, AEs were reported in 97% of patients in the combination arm (n = 207), 93% in the monotherapy arm (n = 215), and 64% in the active monitoring arm (n = 340). Grade 3/4 AEs occurred in 41%, 30%, and 9% of patients, respectively. Serious AEs were observed in 34%, 19%, and 6% of patients, respectively.

AEs led to treatment discontinuation in 29% of patients in the combination arm and 19% in the monotherapy arm. Notably, 2 fatal immune-mediated AEs of myasthenia gravis occurred in the combination arm and 1 instance of fatal myocarditis occurred in the monotherapy arm, treatment-related deaths occurred at a rate of less than 1% in each active treatment group.

Systemic corticosteroid use was required in 43% of the combination arm and 23% of the monotherapy arm. The most common AEs in both treatment arms included fatigue/asthenia (60% vs 53%), diarrhea/colitis, rash (41% vs 33%), and pruritus (35% vs 22%).

“There was no statistically significant or clinically meaningful difference in quality of life at month 15 in the trial,” Larkin concluded in his presentation.

Disclosures: Larkin received honoraria from Bristol Myers Squibb, Cancer Research UK, Eisai, GSK, Gynavax, Incyte, iOnctura, Merck Serono, Novartis, Pfizer, Roche, touchEXPERTS, and touchIME. He holds consulting or advisory roles with Apple Tree Partners, Boston Biomedical, Bristol Myers Squibb, Eisai, Immunocore, Incyte, iOnctura, Iovance Biotherapeutics, Merck Serono, MSD Oncology, Novartis, Pfizer, and YKT Corporation. He received research funding from Achilles Therapeutics (Inst), AVEO (Inst), Bristol-Myers Squibb (Inst), Covance (Inst), Immunocore (Inst), MSD (Inst), Nektar (Inst), Novartis (Inst), Pfizer (Inst), Pharmacyclics (Inst), and Roche (Inst). He received travel, accommodations, and expenses from Bristol Myers Squibb/Roche, ESMO, GSK, and Roche/Genentech.

References

1. Larkin J, Powles T, Frangou E, et al. Durvalumab monotherapy versus active monitoring for resected primary renal cell carcinoma in RAMPART: an international, investigator-led, phase 3, randomized controlled trial. J Clin Oncol. 2026;44(suppl 17):LBA4511. doi:10.1200/JCO.2026.44.17_suppl.LBA4511
2. FDA approves Merck’s Keytruda (pembrolizumab) as adjuvant therapy for certain patients with renal cell carcinoma (RCC) following surgery. News release. Merck. November 18, 2021. Accessed May 30, 2026. https://www.merck.com/news/fda-approves-mercks-keytruda-pembrolizumab-as-adjuvant-therapy-for-certain-patients-with-renal-cell-carcinoma-rcc-following-surgery/