Multicenter phase 1 trial of autologous T cell antigen coupler targeting HER2 in advanced or metastatic solid tumors

The T cell antigen coupler (TAC) is a novel genetically engineered receptor that recruits native T cell receptor upon recognition of an antigen. The downstream activation of TAC T cells has been effective against tumors in preclinical models. HER2 is a validated biomarker for cancer-targeted therapy, but cell therapy approaches have been met with unmanageable toxicity. A phase 1 trial In the USA and Canada evaluated TAC01-HER2, an autologous T cell product that targets HER2, in patients with HER2-positive advanced solid tumors. A total of 23 patients were enrolled. The recommended phase 2 dose was 6-8 x 10⁶ per kg. The most common treatment-related adverse events were cytokine release syndrome (60.9% of patients) andincreased alanine aminotransferase (21.7%). No treatment-related deaths or adverse events leading to study discontinuation were reported. Two of 9 patients with gastric and gastroesophageal junction cancers had partial responses, and the disease control rate was 61.1% among the 18 patients with evaluable assessments. The median progression-free survival was 2.6 months (range 0.8-12.4) and the overall survival rate at 6 months was 57.9% (95% CI 36.3-76.9). Persistence of TAC T cells in peripheral blood was observed in all patients until at least day 29 after the first infusion. The authors conclude that TAC01-HER2 showed manageable toxicity and early efficacy for heavily pretreated patients with HER2-positive gastric and gastroesophageal junction adenocarcinoma.