Immune checkpoint inhibitor combinations have become a standard component of treatment for advanced renal cell carcinoma. However, the optimal duration of immunotherapy remains uncertain, particularly for patients who achieve an early and meaningful response.
Long-term results from the OMNIVORE trial suggest that selected patients responding early to nivolumab may maintain disease control for several years after treatment discontinuation. Conversely, adding ipilimumab after failure to respond to nivolumab produced limited benefit.
The article, titled “Long-term follow-up from the OMNIVORE trial: response-adaptive nivolumab and ipilimumab in advanced renal cell carcinoma,” was published in the Journal for ImmunoTherapy of Cancer, Volume 14, Issue 7, on July 1, 2026.
Authors: Rana R. McKay, Michael Serzan, Wanling Xie, Bradley A. McGregor, David Braun, Xiao Wei, Christos Kyriakopoulos, Yousef Zakharia, Benjamin L. Maughan, Tracy Rose, Walter M. Stadler, David F. McDermott, and Toni K. Choueiri.
A Response-Adapted Treatment Strategy
OMNIVORE was a multicenter, phase II trial evaluating whether treatment could be adapted according to the initial response to nivolumab.
Patients with advanced renal cell carcinoma first received nivolumab monotherapy. Treatment allocation was determined by radiographic response within the first 6 months:
- Patients with a confirmed complete or partial response discontinued nivolumab and entered active observation in Arm A.
- Patients with stable or progressive disease continued nivolumab and received two additional doses of ipilimumab in Arm B.
The trial had two primary objectives: to determine the proportion of early responders who remained progression-free and treatment-free at 1 year after nivolumab discontinuation, and the proportion of non-responders who achieved a confirmed objective response after ipilimumab was added.
Eligible patients had unresectable, locally recurrent, or metastatic renal cell carcinoma of any histologic subtype. Previous systemic treatment was permitted, although prior exposure to a PD-1 pathway or CTLA-4 inhibitor was not allowed.
Read more about Kidney Cancer Cure Rate and Survival Outcome on OncoDaily.
Patient Population
A total of 83 patients initiated nivolumab across 10 centers in the United States.
Most patients were male, had an ECOG performance status of 0 or 1, and had clear-cell renal cell carcinoma. Approximately half were treatment-naive, while 67% had intermediate- or poor-risk disease according to the International Metastatic Renal Cell Carcinoma Database Consortium criteria.
Of the 83 treated patients:
- 12 were allocated to Arm A after an early response.
- 57 were allocated to Arm B after stable or progressive disease.
- 14 were not allocated because of early progression or toxicity.
Among living patients, median follow-up was 32.2 months for the overall cohort, 59.4 months for Arm A, and 31.4 months for Arm B.
Long-Term Survival
The estimated 3-year overall survival rate from the start of nivolumab was:
- 64% in the overall population.
- 83% in Arm A.
- 63% in Arm B.
Although survival appeared higher among early responders assigned to treatment discontinuation, the small number of patients and non-randomized design prevent a direct comparison between the two groups.
Read about Nivolumab (Opdivo) on OncoDaily.
Prolonged Treatment-Free Survival in Early Responders
Among the 12 patients in Arm A, six, or 50%, remained off nivolumab at 1 year after treatment discontinuation. Five of these patients maintained their responses for more than 43 months without nivolumab. Their observation periods ranged from 43.8 to 58.2 months, and all five were alive at their most recent follow-up. Overall survival among these patients ranged from 48.8 to 85.4 months from the start of nivolumab.
The other six patients experienced progression or restarted nivolumab within 1 year. Only one subsequently achieved a durable complete response. This patient had restarted nivolumab while still in partial response, representing a protocol violation, and remained on treatment 83.2 months after nivolumab initiation.
Patients who received nivolumab plus ipilimumab after progression following treatment discontinuation generally experienced limited benefit.
Limited Activity From Salvage Ipilimumab
All 57 patients in Arm B eventually discontinued treatment. Median treatment duration was 3.7 months. Median progression-free survival from the addition of ipilimumab was 4.6 months, with a 95% confidence interval of 2.7–6.5 months.
The initial OMNIVORE analysis had previously shown a response-conversion rate of only 4% after salvage ipilimumab, with no complete responses. The extended results reinforce that sequentially adding ipilimumab after an inadequate response to nivolumab is unlikely to reproduce the benefit associated with upfront concurrent nivolumab and ipilimumab.
Clinical Interpretation
The findings raise the possibility that continuous or prolonged PD-1 inhibition may not be necessary for some carefully selected patients who achieve an early response. A small subgroup maintained tumor control for more than 4 years after receiving only a relatively short course of nivolumab.
However, these results should not be interpreted as evidence supporting routine early discontinuation of immunotherapy. Only 12 patients entered the discontinuation arm, the trial did not include a randomized comparator, and some patients were lost to extended follow-up. The study also did not identify a validated clinical or molecular marker capable of predicting which responders could safely stop treatment.
Prospective randomized trials incorporating tissue and circulating biomarkers will therefore be needed to determine whether response-guided discontinuation can be introduced into clinical practice.
You can also read about ICI Rechallenge in Metastatic Clear-Cell RCC on OncoDaily.
Conclusion
Long-term follow-up from OMNIVORE shows that selected patients with advanced renal cell carcinoma who achieve an early response to nivolumab may experience prolonged treatment-free survival after stopping therapy, with several remaining off treatment for more than 4 years.
These findings are hypothesis-generating and support further investigation of biomarker-guided immunotherapy discontinuation. They do not yet establish early nivolumab discontinuation as a standard strategy.
For patients who do not respond to nivolumab monotherapy, the limited activity observed with delayed ipilimumab supports the continued use of upfront concurrent dual checkpoint blockade when nivolumab plus ipilimumab is selected.
Trial registration: NCT03203473.
The full article is available in the Journal for ImmunoTherapy of Cancer.