Long-Term Follow-Up Of Pharmacokinetics (Pk) And Immunogenicity Of The Anti-Pd-1 Antibodies Nivolumab (Nivo) And Pembrolizumab (Pembro) In Real-World Practice.

3120 Background: The PD-1 blockers Nivo and Pembro are widely used to treat patients (pts) with various types of cancer, but their PK and immunogenicity have not been adequately characterized in clinical practice. Here we report the first long-term follow-up of PK and anti-drug antibodies (ADAs) of Nivo and Pembro, correlated with efficacy and safety. Methods: We included 147 pts receiving Nivo (n = 98) or Pembro (n = 49) between May 2016 and Jan 2019. Plasma samples were longitudinally collected before each infusion and after discontinuation for as long as samples were obtainable. Drug concentrations were measured by ELISA (LLOQ: 0.0125 µg/mL), and ADAs were evaluated by bridging ELISA. Results: Median (range) follow-up was 6.0 (0.1-38.7) mo, and 1718 samples were analyzed. ADAs were confirmed at baseline or at last sample for both Nivo (2 [2.2%] and 4 [4.5%] pts, respectively) and Pembro (2 [4.2%] and 3 [6.7%] pts). Of the 4 baseline ADA-positive pts, 3 experienced drug-induced fever after initial infusion. Pts developing ADAs at last sample had earlier progression than ADA-negative pts (median PFS: 46 vs. 119 days, log-rank P = 0.0827). Persistent drug exposure until ~1 y beyond discontinuation was observed for both drugs. In 1 Nivo-treated pt with delayed adrenal insufficiency 8.6 mo after discontinuation, Nivo was still detectable (0.2 µg/mL). In 71 and 41 efficacy-evaluable pts receiving Nivo and Pembro, respectively, mean trough levels in the early period (~cycle 6) were significantly higher in pts achieving response than in pts with progressive disease at first assessment (Nivo: 43.5 vs. 31.0 µg/mL, P = 0.0107; Pembro: 30.6 vs. 22.1 µg/mL, P = 0.0174). Conclusions: Our findings provide insight into the etiological mechanism of late-onset adverse events associated with PD-1 blockers. Moreover, ADA may potentially influence clinical outcomes, and it may be possible to optimize dose in certain pts with lower drug exposure for improved efficacy, warranting further investigation. Clinical trial information: UMIN000033036. [Table: see text]