Ipilimumab Yields ‘Limited Effect’ in Refractory Kidney Cancer Subtype

Ipilimumab monotherapy does not appear effective in driving complete responses in refractory renal cell carcinoma despite yielding some progression-free survival intervals, according to an expert from the University of Texas Southwestern Medical Center.

In an interview with CancerNetwork® during the 2023 Genitourinary Cancers Symposium, Tian Zhang, MD, MHS, discussed how previous clinical trial results highlight the limited efficacy of ipilimumab (Yervoy) as treatment for patients with refractory renal cell carcinoma.

Zhang, an associate professor in the Department of Medicine at Harold C. Simmons Comprehensive Cancer Center of the University of Texas Southwestern Medical Center, discussed how it is not standard to add ipilimumab to nivolumab (Opdivo) in this patient population despite some benefit in terms of progression-free survival (PFS) and partial responses.


We now have 4 phase 2 trials evaluating ipilimumab for patients with stable disease or refractory disease while on nivolumab. This includes the phase 2 Titan-RCC trial [NCT02917772]; which was] initially done in a European population with an ipilimumab boost for patients who had stable disease or progressive disease on nivolumab.1

We have a trial called phase 2 FRACTION-RCC [NCT02996110] in which patients who had prior PD-1–, PD-L1–, or CTLA-4–directed therapies were [randomly assigned to] treatment with the combination of ipilimumab and nivolumab.2

Then we have an investigator-led trial called the phase 2 OMNIVORE trial [NCT03203473] where patients with nivolumab induction went on to receive ipilimumab if they had confirmed stable disease or progressive disease.3 Finally, the fourth trial was a Hoosiers Network trial called the phase 2 CheckMate 669 study [NCT03117309], which also treated patients with ipilimumab or patients who had progressive disease or best response as stable disease at 48 weeks, so a prolonged period of stable disease on nivolumab.4

All 4 of these trials have now completed and reported. Most of them have shown us that there is a limited effect of driving complete responses by adding ipilimumab in the refractory setting. We do see some progression-free survival intervals, and we do see also some partial responses for these patients who do get ipilimumab added. But for the most part, it is not standard practice to add ipilimumab to nivolumab [for] refractory renal cell carcinoma.


  1. Grimm M, Gonzalez EE, Barthelemy P, et al. Efficacy of a tailored approach with nivolumab and nivolumab/ipilimumab as immunotherapeutic boost in metastatic renal cell carcinoma: Final results of TITAN-RCC. Ann Oncol. 2022;33(suppl 7):S660-680. doi: 10.1016/annonc/annonc1072
  2. Choueiri TK, Kluger H, George S, et al. FRACTION-RCC: nivolumab plus ipilimumab for advanced renal cell carcinoma after progression on immuno-oncology therapy Journal for ImmunoTherapy of Cancer. 2022;10:e005780. doi: 10.1136/jitc-2022-005780
  3. McKay RR, McGregor BA, Xie W, et al. Optimized management of nivolumab and ipilimumab in advanced renal cell carcinoma: a response-based phase II study (OMNIVORE). J Clin Oncol. 2020;38(36):4240-4248. doi:10.1200/JCO.20.02295
  4. Atkins MB, Jegede OA, Haas NB, et al. Phase II study of nivolumab and salvage nivolumab/ipilimumab in treatment-naïve patients with advanced clear cell renal cell carcinoma (HCRN GU16-260-Cohort A). J Clin Oncol. 2022;40(25):2913-2923. doi:10.1200/JCO.21.02938
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