Authors:

Lin Shen¹, Zhenling Yao², Dongmei Chen³, Michael Yu², Xu-Alan Lin³, Charlie Qi³, Simon Xia³, Lijuan Zhang³, Steven Yu³, Caroline Germa^2
1Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China; ²Global R&D, Transcenta Therapeutics Inc., Princeton, United States of America; ³Global R&D, Suzhou Transcenta Therapeutics Co. Ltd., Suzhou, China
Background

Osemitamab (TST001), a humanized Claudin18.2 monoclonal antibody with enhanced antibodydependent cellular cytotoxicity (ADCC) via improved binding affinity and reduced fucosylation, is being developed to treat advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma. Pharmacokinetics (PK), pharmacodynamics (PD) and exposure-response (ER) relationship of Osemitamab were evaluated in two phase I/IIa studies. PK exposure increased with osemitamab dose and the effective half-life was approximately 4 to 7 days¹.

Summary and Conclusions

• ER analyses found that patients had shorter PFS/DoR with PK exposures (dose range from 1-8mg/kg) within lowest tertile (C_avg < ~ 20 µg/mL and C_{trough_ss} < ~ 7ug/mL)
• PopPK modeling indicated 6 mg/kg Q3W or 4mg/kg Q2W cohorts are expected to have higher proportion of subjects (4-5 folds when compared with 3 mg/kg Q3W or 2 mg/kg Q2W) achieving PK exposures associated with better PFS/DoR
• Safety ER analyses didn’t demonstrate clinically significant increase in risk when dose increased from 3 to 6 mg/kg Q3W
• Preliminary efficacy, safety and PK/PD data demonstrates favorable benefit risk profile and support future exploration of osemitamab at the recommended dose of 6mg/kg Q3W or 4mg/kg Q2W