This study is a first-in-human, three-stage, phase 1 trial (NCT05154604) designed to evaluate the trophoblast cell-surface antigen 2 (TROP-2)-targeted antibody-drug conjugate SHR-A1921 (1.5-6.0 mg/kg every 3 weeks) in 391 patients with pretreated advanced/metastatic solid tumors. Grade ≥3 treatment-related adverse events occurred in 132 patients (33.8%), with the most common being stomatitis, affecting 57 patients (14.6%). SHR-A1921 showed a low incidence of hematologic toxicities, with only 3.1% of patients experiencing grade ≥3 decreases in neutrophil count. The overall objective response rate was 24.8% (95% confidence interval [CI], 20.6-29.4), ranging from 18.2% to 43.1% across cohorts with platinum-resistant ovarian cancer, triple-negative breast cancer, small-cell lung cancer, non-small cell lung cancer, hormone receptor-positive breast cancer, cervical cancer, and biliary tract cancer. No significant correlation was found between TROP-2 expression and treatment efficacy. In summary, SHR-A1921 exhibited promising antitumor activity and a manageable safety profile, with 3.0 mg/kg every 3 weeks selected for further clinical development.
Functional cancer-to-neuron synapse-like connections are recognized as essential structures and hallmarks of both intracranial and extracranial tumors. In this issue of Cancer Cell, Ren et al. present high-resolution EM structures of pseudo-synaptic connections between sensory nerves and pancreatic ductal adenocarcinoma (PDAC).

