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Using Pharmacokinetic and Pharmacodynamic Analysis to Optimize the Dosing Regimens of Fanastomig (EMB-02) in Patients

Chengjun Jiang1, Fang Ren1, Mingfei Zhang1

  • 1Hanghai EpimAb Biotherapeutics Co., Ltd, Shanghai EpimAb Biotherapeutics, Shanghai, China.

CPT: Pharmacometrics & Systems Pharmacology
|March 11, 2025
PubMed

Insights

Fanastomig, a novel bispecific antibody for advanced solid tumors, demonstrated good tolerability and safety in a Phase I trial. Recommended Phase II dosing was established using population pharmacokinetics and exposure-response modeling.

Area of Science:

  • Immunotherapy
  • Pharmacology
  • Oncology

Background:

  • Fanastomig (EMB-02) is a bispecific antibody targeting PD-1 and LAG-3 for advanced solid tumors.
  • A first-in-human Phase I study evaluated its safety, PK, PD, immunogenicity, and efficacy.

Purpose of the Study:

  • Determine the recommended Phase II dose (RP2D) for Fanastomig.
  • Conduct population pharmacokinetic (PopPK) and exposure-response (E-R) analyses.
  • Assess Fanastomig's safety, tolerability, and clinical efficacy in advanced solid tumors.

Main Methods:

  • Population pharmacokinetic (PopPK) modeling to assess drug exposure and covariate relationships.
  • Nonlinear Emax modeling to determine PD-1 receptor occupancy (RO) and EC50.
  • Modeling and simulation to identify optimal dosing regimens (e.g., weekly dosing).
  • Analysis of anti-drug antibody (ADA) incidence and impact on PK/efficacy.

Main Results:

  • PopPK model showed no significant covariate impact on Fanastomig exposure (AUC, Cmax).
  • Estimated EC50 for PD-1 RO was 0.084 μg/mL; target trough concentration for 90% tumor RO is ~2.27 μg/mL.
  • A weekly dose of 360 mg is predicted to achieve full peripheral blood RO in ~90% of patients.
  • High ADA incidence (95.7%) had minimal impact on PK/efficacy; anaphylaxis showed an inverse trend with PK exposure.
  • Fanastomig was well tolerated up to 900 mg QW, with an acceptable safety profile.

Conclusions:

  • Two dosing regimens were selected for further clinical development based on safety, PK, and PD data.
  • Fanastomig shows promise as a well-tolerated immunotherapy for advanced solid tumors.
  • The study successfully established a foundation for further investigation of Fanastomig in Phase II trials.
Keywords:
Fanastomigdose optimizationexposure and responselympahocyte activation gene‐3 (LAG‐3)population pharmacokinetic modelprogrammed cell death protein 1 (PD‐1)receptor occupancy

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