Y. Feng, X. Wang, S. Agrawal, B. Lestini, J. Park, A. Roy; Bristol-Myers Squibb, Princeton, NJ

BACKGROUND: Nivolumab, a fully human IgG4 monoclonal antibody, selectively binds to programmed death-1 (PD-1) receptor that blocks the interaction between PD-1 and its ligands to promote an antitumor immune response. The purpose of this analysis was to characterize the relationship between nivolumab exposure and measures of efficacy in squamous (SQ) NSCLC subjects and safety in subjects with advanced solid tumors.
METHODS: The E-R relationship between nivolumab exposure (trough concentration after dose 1 [Cmin1]) and objective response (OR; per RECIST 1.1, defined as best overall response of partial response or complete response) was characterized by a logistic regression model with data from a phase II study in advanced refractory SQ NSCLC subjects who received nivolumab 3 mg/kg every 2 weeks (Q2W) (N=91). The E-R of safety (Grade 3+drug related adverse events (DR-AEs) and AEs leading to discontinuation [AE-DC]) was characterized by two separate semi-parametric Cox proportional hazards models, with respect to time-averaged steady-state concentration (Cavgss) in advanced solid tumors subjects receiving 0.1-10 mg/kg Q2W nivolumab (N=410).
RESULTS: Nivolumab Cmin1 produced by 3 mg/kg Q2W was not a significant predictor of the probability of achieving an OR (odds ratio: 1.947 and 95%CI: 0.106-35.7). Risk of Grade 3+ DR-AEs (hazard ratio (HR): 0.98 and 95%CI: 0.817-1.18) and AE-DC (HR: 1.07, and 95%CI: 0.867, 1.33) was not increased with log(Cavgss) produced by nivolumab doses of 0.1 to 10 mg/kg Q2W.
CONCLUSION: Nivolumab efficacy did not increase across the exposures produced by 3 mg/kg Q2W dosing regimen in advanced refractory SQ NSCLC patients, and the exposures produced by nivolumab doses of 0.1 to 10 mg/kg Q2W were not a significant predictor of safety in patients with advanced solid tumors.