Author of

• 18502

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  P3.02c - Poster Session with Presenters Present (ID 472)

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: Advanced NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 18532

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    P3.02c-030 - Use of a 200-Mg Fixed Dose of Pembrolizumab for the Treatment of Advanced Non–Small Cell Lung Cancer (NSCLC) (ID 6129)

    14:30 - 14:30  |  Author(s): M.E. O'Brien
    • Abstract

    Background:
    Previous analyses showed no clinically significant exposure-efficacy relationship for pembrolizumab doses of 2-10 mg/kg. Population pharmacokinetics (popPK) modeling suggested weight-based or fixed pembrolizumab doses could maintain exposures within the established safety/efficacy bounds. Fixed dose advantages include increased convenience, reduced dosing error risk, and less discarded product. Pembrolizumab 200 mg Q3W was evaluated in the KEYNOTE-024 study of pembrolizumab versus platinum-doublet chemotherapy for treatment-naive advanced NSCLC with PD-L1 TPS ≥50% (NCT02142738).
    
    Methods:
    Pembrolizumab serum concentration was quantified with an electrochemiluminescence-based immunoassay (lower limit of quantitation, 10 ng/mL). The existing 2-compartment popPK model derived from studies of weight-based pembrolizumab dosing was extended with KEYNOTE-024 concentration-time data. Correlation between pembrolizumab exposure (ie, area under the serum-concentration curve over 6 weeks [AUC~ss-6weeks~]) and efficacy was assessed.
    
    Results:
    Median (range) weight was 69.7 kg (38-110) in KEYNOTE-024 and 75 kg (35.7-210) in the existing popPK model studies. In treatment-naive advanced NSCLC, there was a flat relationship between pembrolizumab exposure and efficacy for the 200-mg fixed dose and weight-based doses (linear regression P>0.05). Observed pembrolizumab concentrations for 200 mg (median 1976 μg·d/mL, 90% CI 1124-3322) were consistent with predictions (median 1751 μg·d/mL, 90% prediction interval 955-3136) and fell within the previously observed therapeutic window for 2 and 10 mg/kg (Figure). There was considerable overlap in exposures for 2 mg/kg and 200 mg, regardless of whether weight was >90 or <90 kg for 200 mg (Figure). Figure 1
    
    
    
    Conclusion:
    Pembrolizumab exposure at 200 mg Q3W is similar to that of 2 mg/kg Q3W. Including data from patients with advanced NSCLC treated with 200 mg did not change the flat exposure-efficacy relationship. Along with the superior PFS and OS provided by pembrolizumab over platinum-doublet chemotherapy as first-line therapy for advanced NSCLC with TPS ≥50%, these data support 200 mg Q3W as an alternative to the approved 2-mg/kg Q3W dose.