Authors:

Anthony Tolcher¹, Nashat Gabrail², Minal Barve³, Xiaohua Wu⁴, Jian Zhang⁴, Michael Shi⁵, Chuan Qi⁵, Lei Chen⁵, Steven Yu⁵, Jenny Yao⁵, Jianming Wang⁵, Christopher T. Cavanaugh⁵

¹NEXT Oncology, San Antonio, TX, USA; 

²Gabrail Cancer, Canton, OH USA; 

³Mary Crowley Cancer Research Centers, Dallas TX, USA; 

⁴Fudan University Shanghai Cancer Center, Shanghai, P. R. China; 

⁵Suzhou Transcenta Therapeutics Co., Ltd, Suzhou, Jiangsu, P. R. China

Background:

Anti-programmed death 1 / ligand 1 (PD-1/PD-L1) therapies have been established as standard treatment for multiple tumor types.However,the key challenge of these therapies is resistance caused by immunosuppressive factors in the tumor microenvironment (TME). TGF-β is a multi-functional cytokine that is involved in the tight regulation of either antitumor immunity or tumor immunosuppression. TGF-β promotes an immune exclusion TME thus renders PD-L1 blockade ineffective. Therefore, dual targeting PD-L1 and TGF-β represents a rational synergistic strategy to enhance clinical outcome relative to each agent alone.

TST005 is a novel bi-functional fusion protein combining a high affinity PD-L1 monoclonal antibody (mAb) in a fragment crystallizable (Fc) silenced immunoglobulin G1 (IgG1) backbone and a differentiated transforming growth factor beta (TGF-β) trap with improved stability. This study will investigate TST005's safety, tolerability and preliminary anti-tumor activity in solid tumors.

Study Status:

This study is ongoing at 4 sites in the US and China. As of the 24 Aug 2022, the first three dose cohorts has been completed the evaluation and no DLT was observed. Clinical trial information: NCT04958434. Study Sponsor: Suzhou Transcenta Therapeutics Co., Ltd.