Long-Term OMNIVORE Data Show Durable Treatment-Free Survival in RCC

With more than 5 years of follow-up, a phase 2 response-adaptive trial has found that half of patients with advanced renal cell carcinoma (RCC) who achieved an early objective response to nivolumab (Opdivo) monotherapy remained off treatment 1 year after discontinuation, and most of those patients sustained their responses for years without further therapy, according to results published in the Journal for ImmunoTherapy of Cancer.¹

The extended analysis of the OMNIVORE trial (NCT03203473), led by Rana R. McKay, MD, of the University of California San Diego, and colleagues, also confirmed that adding salvage ipilimumab (Yervoy) in patients who did not respond to nivolumab induction provided limited additional benefit, reinforcing that upfront combination checkpoint blockade remains the preferred first-line strategy in this population.

Study Design

OMNIVORE enrolled 83 patients with advanced RCC across 10 US centers who received induction nivolumab monotherapy, with subsequent treatment allocated according to radiographic response within the first 6 months. Patients who achieved a confirmed complete or partial response discontinued nivolumab and entered observation (arm A, n = 12), while those with stable or progressive disease received 2 doses of ipilimumab added to ongoing nivolumab (arm B, n = 57). Fourteen patients did not undergo arm allocation because of early progression or toxicity.

Key Findings

At a database lock of April 28, 2025, median follow-up among living patients was 32.2 months for the overall cohort, 59.4 months in arm A, and 31.4 months in arm B. The 3-year overall survival (OS) rate from nivolumab initiation was 64% for the full cohort, 83% in arm A, and 63% in arm B.

Among the 12 arm A patients, 6 (50%; 90% CI, 25%-75%) remained off nivolumab 1 year after discontinuation. Of these, 5 maintained responses beyond 43 months off therapy, with observation periods extending to 58.2 months; all 5 were alive at last follow-up, with OS ranging from 48.8 to 85.4 months from nivolumab initiation. One additional patient reinitiated nivolumab while technically still in partial response—a protocol violation—and went on to achieve a complete response, remaining on treatment at 83.2 months. Overall, 9 of 12 arm A patients remained alive at data cutoff.

In arm B, all 57 patients discontinued treatment, with a median treatment duration of 3.7 months. Median progression-free survival from nivolumab-plus-ipilimumab initiation was 4.6 months (95% CI, 2.7-6.5), and 21 deaths were reported in this arm. These findings are consistent with a prior pooled analysis of OMNIVORE, TITAN-RCC, and HCRN GU16-260, which found only a 12.6% objective response rate with salvage nivolumab-ipilimumab in nivolumab nonresponders.²

Clinical Implications

The authors noted that OMNIVORE extends observations from the CheckMate 214 trial (NCT02231749) of frontline nivolumab-ipilimumab, in which a substantial proportion of patients achieving complete responses remained treatment free for years after discontinuation.³ The current data suggest that even a short induction course of single-agent nivolumab—rather than sustained combination therapy—may be sufficient to produce lasting immune-mediated tumor control in select responders.

Limitations

The authors cautioned that the small number of patients in arm A, the absence of a randomized comparator, and loss to follow-up among some patients limit definitive conclusions about the discontinuation strategy.¹ Correlative biomarker analyses from OMNIVORE—including clonal neoantigen burden, T-cell exhaustion markers, and circulating tumor DNA kinetics—are pending and may help identify which patients can safely stop therapy. The authors called for prospective, biomarker-driven randomized trials to formally evaluate treatment discontinuation approaches in advanced RCC.

REFERENCES

1. McKay RR, Serzan M, Xie W, et al. Long-term follow-up from the OMNIVORE trial: response-adaptive nivolumab and ipilimumab in advanced renal cell carcinoma. J Immunother Cancer. 2026;14:e015501. doi:10.1136/jitc-2026-015501

2. McKay RR, Leucht K, Xie W, et al. A pooled analysis of 3 phase II trials of salvage nivolumab/ipilimumab after nivolumab in renal cell carcinoma. Oncologist. 2024;29:324-331. doi: 10.1093/oncolo/oyad298

3. Choueiri TK, Albigès L, McDermott DF, et al. Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: final analysis of efficacy and safety from the phase III CheckMate 214 trial. Ann Oncol. 2026;37:960-973. doi: 10.1016/j.annonc.2026.02.017