First-in-human phase 1 trial of the HER2 biparatopic antibody-drug conjugate TQB2102 in patients with advanced solid tumors

TQB2102 is a next-generation biparatopic antibody-drug conjugate targeting HER2 extracellular domain 2 and 4 isotopes, conjugated to a topoisomerase I payload. A first-in-human phase 1 trial at 12 centers in China evaluated TQB2102 in patients with advanced solid tumors. Between March 2023 and January 2025, 195 patients were enrolled, mainly including metatatic breast cancer (n=80), colorectal cancer (n=37), and gastric/gastroesophageal junction adenocarcinoma (n=37). Patients received intravenous TQB2102 once every 3 weeks, in doses for 1.5 to 9.0 mg/kg. No dose-limiting toxicities occurred and the maximum tolerated dose was not reached. Recommended phase 2 dose was selected as 6.0 and 7.5 mg/kg every 3 weeks. The most common grade ≥ 3 treatment-related adverse events were decreases of neutrophil count (23.2%), WBC count (10.8%), and lymphocyte count (8.2%), and anemia (8.8%). Only one patient had drug-related interstititial lung disease. The objective response rate was attained in patients with HER2-positive tumors, including metastatic breast cancer (52.4%), colorectal cancer (38.7%), and G/GEJ adenocarcinoma (40.0%). Of note, patients with HER2-low metastatic breast cancer achieved an ORR of 47.2%. The ORR was 70% in HER2-positive and 50.0% in HER2-low breast cancer with brain metastases. The authors conclude that TQB2102 demonstrated a manageable safety profile and preliminary antitumor activity in advanced solid tumors.