PII-118

C. Passey, J. Simon, Q. Hong, A. Roy, S. Agrawal; Bristol-Myers Squibb, Princeton, NJ

BACKGROUND: Nivolumab is a fully human IgG4 monoclonal antibody (mAb) that targets the programmed death-1 receptor expressed on activated T cells. Although the potential for drug interactions between a mAb and small-molecule drugs is low, mAbs that modulate cytokines may indirectly affect expression of cytochrome P450 (CYP) enzymes, which may affect exposure of a small-molecule drug. This analysis aimed to evaluate drug interaction potential of nivolumab using cytokine modulation data.
METHODS: The effect of nivolumab on cytokine modulation was assessed by measuring cytokine levels following nivolumab doses of 0.3, 2, and 10 mg/kg every 3 weeks. Cytokine levels were measured at Dose 1 (0, 3, 7, and 24 h), Dose 2 (0 and 168 h), and Dose 4 (0 h). The following cytokines known to modulate CYP enzymes were assessed using a multiplexed immunoassay platform: interleukin (IL)-2N, soluble IL-2 receptor α, IL-1A, IL-1B, IL-6, IL-10, interferon-γ, tumor necrosis factor-α, IL-12P, and IL-23M.
RESULTS: With the exception of IL-6, IL-10, and IL-2, all other cytokines were below the lower limit of quantification. There was no considerable change in IL-6, IL-10, and IL-2 during the course of treatment. No systematic changes were observed in studied cytokines. Transient changes were observed in the cytokine levels in few individuals but were not consistent in magnitude and/or direction of change within an individual. These changes also did not correspond to any particular time post-treatment initiation. Lack of cytokine modulation known to affect CYP expression was seen for all nivolumab dose levels (0.3, 2, and 10 mg/kg).
CONCLUSION: Overall, the lack of cytokine modulation suggests that nivolumab has no or low potential for modulating CYP enzymes, and thus has a low risk of therapeutic protein-drug interaction.