Biomarker analysis of the phase 2 TITAN-RCC trial identified specific immune cell-related parameters that are associated with efficacy of nivolumab (± ipilimumab) for the treatment of patients with advanced or metastatic clear-cell renal cell carcinoma (RCC).


Despite promising therapeutic efficacy of immune checkpoint inhibitors in RCC, response varies significantly between individual patients. Therefore, predictors of response are urgently needed. The open-label, phase II TITAN-RCC trial (NCT02917772) investigates nivolumab monotherapy with additional nivolumab/ipilimumab “boost” cycles in previously untreated and pre-treated patients with advanced or metastatic RCC with intermediate- and high-risk disease. Participants received nivolumab induction until week 16 and continued with nivolumab maintenance upon remission. Patients who had stable disease or progressive disease or early progressive disease at week 8 continued up to four cycles of nivolumab plus ipilimumab.

A Closer Look at TITAN-RCC

Nivolumab maintenance was then continued in these patients. Blood samples for biomarker and phenotype analyses were taken at baseline, during nivolumab induction, and during nivolumab/ipilimumab boost cycles. Dr. Michael-Oliver Grimm (University Hospital Jena, Germany) presented the results.1 A total of 207 patients were enrolled in TITAN-RCC of whom 137 received the nivolumab/ipilimumab boost. Responders to nivolumab induction are characterized by a higher proportion of 4-1BB- or LAG-3-expressing T cells at baseline.

Various Immune Cell-Related Parameters Identified

Adjusted odds ratios for percentages in responders to nivolumab induction versus non-responders were 1.03 for 4-1BB+CD8+, 1.05 for 4-1BB+CD4+, and 1.0 for LAG-3+CD4+, respectively. Moreover, in patients receiving nivolumab plus ipilimumab boosts, a higher proportion of PD-L1+CD14+ monocytes, PD-L1+ early-stage myeloid-derived suppressor cells, and PD-L1+ plasmacytoid dendritic cells were observed in responders versus non-responders. Odds ratios were 1.22, 1.14, and 1.08, respectively.

“In conclusion, this biomarker analysis of TITAN-RCC identified various immune cell-related parameters that are associated with increased therapeutic efficacy in RCC patients,” stated Dr. Grimm. “These immune cell parameters may represent novel predictive biomarkers for the response to nivolumab and or nivolumab/ipilimumab therapy in clear-cell RCC.”

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