Biomarkers predict response to immune nivolumab (± ipilimumab) in advanced RCC

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

Despite the 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 2 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. Participants who had stable or progressive disease at week 8 received up to 4 cycles of nivolumab plus ipilimumab. 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 Marc-Oliver Grimm (University Hospital Jena, Germany) presented the results [1].

TITAN-RCC enrolled 207 patients of whom 137 received the nivolumab/ipilimumab boost. Responders to nivolumab induction were characterised by a higher proportion of activated T cells (expressing 4-1BB or LAG-3) at baseline. 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⁺. 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. The 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 nivolumab/ipilimumab therapy in clear-cell RCC.”

1. Grimm M-O, et al. Novel predictive biomarkers of response to immune checkpoint blockade with nivolumab ± ipilimumab in the TITAN-RCC phase 2 trial. Abstract 367, ASCO GU 2022, 17–19 February.

 

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Posted on 8 April, 2022