Modeling to Support Dose Justification for Anti-PD-L1 Clinical Candidate CK-301 in Oncology Patients

Collaboration with Checkpoint Therapeutics


  • A semi-mechanistic pharmacokinetic/target-occupancy (PKTO) model was developed with in vitro, preclinical and clinical data to facilitate dose selection of CK-301 (also known as TG-1501, cosibelimab), an anti-PD-L1 monoclonal antibody (mAb), for ongoing and future clinical trials in oncology patients.
  • The model was used to compare the PK and tumor target occupancy (TO) at steady state under various dosing regimens with cosibelimab to those with three marketed anti-PD-L1 mAbs (ie. atezolizumab, durvalumab and avelumab)

Model Diagram & Development


Model Diagram

Ø indicates degradation/elimination of the indicated species in the model.

Model Description

The main reactions included in model (in all three compartments unless otherwise indicated):

  • PD-L1, sPD-L1 and PD1 are constantly synthesized and degraded, and the equilibrium has been reached before dosing. • PD-1 binds to both PD-L1 and sPD-L1 reversibly.
  • Drug binds to both PD-L1 and sPD-L1 reversibly. 
  • Drug-PD-L1 complex is degraded with the same rate constant as PD-L1.
  • Drug and drug-sPD-L1 complex are eliminated in central compartment.
  • Drug, sPD-L1 and drug-sPD-L1 complex transport across the compartments.


  • With cosibelimab (also known as CK-301) IV dosing of 800 and 1200 mg q2w or q3w, a >99% TO is expected throughout the dosing interval, comparable to TO achieved with atezolizumab at 1200 mg q3w, and durvalumab at 10 mg/kg q2w. 
  • Relative to atezolizumab and durvalumab treatments, similar percentages of patients would possibly benefit from cosibelimab treatment, under the assumption that cosibelimab has similar PK variability

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