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Nivolumab monotherapy produced a modest response rate in patients with nccRCC, with higher response rates observed in patients with higher PD-L1 expression.

In 2015, the FDA approved nivolumab monotherapy for treating clear cell renal cell carcinoma (ccRCC) patients who are resistant to vascular endothelial growth factor receptor tyrosine kinase inhibitors. A trial examined the effectiveness of nivolumab monotherapy and nivolumab/ipilimumab salvage therapy in patients with non-clear cell renal cell carcinoma (nccRCC), a patient population that has not shown significant response to immunotherapy. The findings are published in the Journal for ImmunoTherapy of Cancer.

Patient Enrollment and Eligibility for Salvage Therapy 

In the trial, 35 patients with nccRCC were enrolled. The median follow-up time was 22.9 months, during which 17 patients received salvage nivolumab/ipilimumab therapy (Part B). Three of the remaining 18 patients were still responding, and all 18 were off protocol therapy. Thirty-two patients were eligible for salvage therapy, but 15 did not enroll due to symptomatic PD, grade 3–4 toxicity on nivolumab, or other reasons.

Response Rates of Nivolumab Monotherapy

Histology response data showed five responses out of 35 patients, resulting in a Response Evaluation Criteria in Solid Tumours (RECIST) objective response rate (ORR) of 14.3%, with two complete responses (CRs). The immune-related ORR was 22.9%. Response rates for patients with papillary, chromophobe, and unclassified tumors were 5.3%, 17%, and 30%, respectively. For those with sarcomatoid tumors, the ORR was 33%, with two patients with unclassified tumors and one patient with a papillary tumor responding.

No responses were observed in the 18 patients with PD-L1 expression <5%, while 27% of patients with PD-L1 >5% and 33% of patients with missing PD-L1 status responded. All responses were initially evident at the 12-week CT scan and confirmed at the 18-week scan. The median duration of response was 20.3 months, with three responses still ongoing at the time of data lock. The median progression-free survival (PFS) was 4.0 months and was similar across all histologic types.

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Safety Results of Nivolumab Monotherapy (Part A)

Grade ≥3 treatment-related adverse events were seen in 7 out of 35 patients (20%) on nivolumab monotherapy.

Response Rates of Salvage Nivolumab/Ipilimumab Therapy

One patient responded out of 17 subjects, for an ORR of 6%. The lone responder had an unclassified/non-sarcomatoid RCC and tumor PD-L1 expression of 1–5%. The median PFS was 2.8 months.

Safety Results of Salvage Nivolumab/Ipilimumab Therapy

Toxicity was seen in 7 out of 17 patients (41.2%), with one patient experiencing sudden death of unclear etiology while on the treatment.

It was concluded that nivolumab monotherapy yielded modest response rates in patients with nccRCC, with higher response rates observed in patients with higher PD-L1 expression. Salvage nivolumab/ipilimumab therapy did not show a significant improvement in response rates. This study highlights the need for further research.


Atkins, M. B., Jegede, O. A., Haas, N. B., McDermott, D. F., Bilen, M. A., Stein, M., Sosman, J. A., Alter, R., Plimack, E. R., Ornstein, M. C., Hurwitz, M., Peace, D. J., Signoretti, S., Denize, T., Cimadamore, A., Wu, C. J., Braun, D., Einstein, D., Catalano, P. J., & Hammers, H. (2023). Phase II study of nivolumab and salvage nivolumab/ipilimumab in treatment-naïve patients with advanced non-clear cell renal cell carcinoma (HCRN GU16-260-Cohort B). J Immunother Cancer, 11(3). https://doi.org/10.1136/jitc-2022-004780