Dose Selection for DuoBody®-PD-L1x4-1BB (GEN1046) Using a Semimechanistic Pharmacokinetics/Pharmacodynamics Model That Leverages Preclinical and Clinical Data

Collaboration with Genmab - Presented at SITC 2021


  • DuoBody®-PD-L1x4-1BB (GEN1046) is an investigational, first-in-class, bispecific antibody designed to elicit an antitumor immune response by simultaneous and complementary blockade of PD-L1 on tumor cells and conditional stimulation of 4-1BB on T cells and NK cells
  • Initial results from dose escalation demonstrated encouraging clinical activity and manageable safety in the ongoing phase 1/2a trial in patients with advanced solid tumors
  • Optimizing target engagement for a bispecific antibody is challenging, as it involves binding with 2 targets and predicting trimer levels in tumors based on affinity of individual arms and target expression
  • A semi-mechanistic PK/PD model that predicts trimer levels and PD-L1 RO in tumors was developed to support GEN1046 dose selection in the expansion part of a phase 1/2 trial

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