Anti-PD-1 vs. Anti-PD-L1 Antibodies - Insights From QSP-Based Meta-Analysis



Checkpoint inhibitors that target PD-1 or PD-L1 have had a profound effect in a variety of cancers, both as a single therapy and in combinations [1]. Currently, four anti-PD-1 and three anti-PD-L1 monoclonal antibodies (mAbs) are FDA-approved [2]. Meta-analyses suggest that anti-PD-1 mAbs may yield better survival outcomes [3, 4], however these conclusions are limited by a lack of direct clinical comparisons between anti-PD-1 and anti-PD-L1 mAbs. A model-based meta-analysis comparing the level of PD-1:PD-L1 complex inhibition these mAbs achieve at their clinical doses can provide insights into their efficacy profiles and identify scenarios where targeting PD-1 could be preferential to PD-L1 or vice-versa.


  • High levels of PD-1:PD-L1 complex inhibition are achieved by the approved molecules
    at their clinical doses.
  • Anti-PD-L1 mAbs achieve slightly higher inhibition than anti-PD-1 mAbs – effect on
    clinical outcomes is unclear.
  • In contrast, literature meta-analysis and [3,4] indicate higher efficacy for anti-PD-1
  • The model suggests that the relative efficacy of anti-PD-1 to anti-PD-L1 mAbs is not
    determinable based on PD-1:PD-L1 complex inhibition alone, and perhaps other
    biological mechanisms not included in the model (e.g., the PD-1:PD-L2 axis as
    suggested in [3]) could explain the higher efficacy of anti-PD-1 mAbs seen in literature
  • Which drug class is better depends on multiple factors including receptor expression,
    target half-lives, and drug affinities, but the overall better efficacy of anti-PD-1 mAbs
    can't be predicted from a model that doesn't include the presence of other PD-1 binding
    targets such as PD-L2.

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