Annals of oncology : official journal of the European Society for Medical Oncology · 2026
Preclinical characterization and phase I results of TQB2102, a first-in-class HER2 biparatopic antibody-drug conjugate, in patients with advanced solid tumors.
СтатьяКлиническое исследование I фазыМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Ruan D Y, Lin S Y, Huang J J, Li Y H, Li N, Qu X J, Du X B, Yin Y M, Yuan Z Y, Shi Y X, Xu F, An X, Hong R X, Xia W, Xue C, Bi X W, Jiang K K, Zheng Q F, Zhang Y Q, Peng J J, Liu Z Y, Xiong H H, Suo A L, Lin R B, Zhang S, Tang S N, Yu Y, Li X, Wang X, Tian X, Lv P, Shen C, Lou L G, Wang L, Zhang Z P, Xu T J, Chen T X, Wang S S, Xu R H
Аннотация
BACKGROUND: TQB2102 is a next-generation biparatopic antibody-drug conjugate targeting human epidermal growth factor receptor 2 (HER2) extracellular domain 2 (ECD2) and ECD4 epitopes that is conjugated to a topoisomerase I inhibitor via an enzyme-cleavable linker. This study evaluated the safety, efficacy, and pharmacokinetics of TQB2102 in patients with advanced solid tumors.
PATIENTS AND METHODS: In this phase I, multicenter, first-in-human trial, patients with advanced solid tumors were recruited from 12 centers in China. Eligible patients received intravenous TQB2102 once every 3 weeks. This phase I trial included a dose-escalation phase (1.5, 3.0, 4.5, 6.0, 7.5, and 9.0 mg/kg) and a dose-expansion phase (6.0 and 7.5 mg/kg). The primary endpoints were to assess the safety and determine the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended phase II dose (RP2D) of TQB2102.
RESULTS: Between 8 March 2023 and 1 February 2025, 195 patients were enrolled, mainly those having metastatic breast cancer (MBC, n = 80), colorectal cancer (CRC, n = 37), and gastric/gastroesophageal junction (G/GEJ) adenocarcinoma (n = 37). No DLTs occurred, and the MTD was not reached. The RP2D was selected as 6.0 mg/kg and 7.5 mg/kg every 3 weeks. The most common grade ≥3 treatment-related adverse events were decreased neutrophil count (23.2%), decreased white blood cell count (10.8%), anemia (8.8%), and decreased lymphocyte count (8.2%). Only one patient (0.5%) had drug-related interstitial lung disease. The objective response rate (ORR) was attained in patients with HER2-positive solid tumors, including MBC at 52.4%, CRC at 38.7%, and G/GEJ adenocarcinoma at 40.0%. Notably, patients with HER2-low MBC achieved an ORR of 47.2%. The ORRs were 70.0% and 50.0% in HER2-positive and HER2-low MBC patients with brain metastases.
CONCLUSIONS: TQB2102 demonstrates a manageable safety profile and preliminary antitumor activity in advanced solid tumors. A phase III trial in patients with HER2-low MBC has been initiated.
PATIENTS AND METHODS: In this phase I, multicenter, first-in-human trial, patients with advanced solid tumors were recruited from 12 centers in China. Eligible patients received intravenous TQB2102 once every 3 weeks. This phase I trial included a dose-escalation phase (1.5, 3.0, 4.5, 6.0, 7.5, and 9.0 mg/kg) and a dose-expansion phase (6.0 and 7.5 mg/kg). The primary endpoints were to assess the safety and determine the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended phase II dose (RP2D) of TQB2102.
RESULTS: Between 8 March 2023 and 1 February 2025, 195 patients were enrolled, mainly those having metastatic breast cancer (MBC, n = 80), colorectal cancer (CRC, n = 37), and gastric/gastroesophageal junction (G/GEJ) adenocarcinoma (n = 37). No DLTs occurred, and the MTD was not reached. The RP2D was selected as 6.0 mg/kg and 7.5 mg/kg every 3 weeks. The most common grade ≥3 treatment-related adverse events were decreased neutrophil count (23.2%), decreased white blood cell count (10.8%), anemia (8.8%), and decreased lymphocyte count (8.2%). Only one patient (0.5%) had drug-related interstitial lung disease. The objective response rate (ORR) was attained in patients with HER2-positive solid tumors, including MBC at 52.4%, CRC at 38.7%, and G/GEJ adenocarcinoma at 40.0%. Notably, patients with HER2-low MBC achieved an ORR of 47.2%. The ORRs were 70.0% and 50.0% in HER2-positive and HER2-low MBC patients with brain metastases.
CONCLUSIONS: TQB2102 demonstrates a manageable safety profile and preliminary antitumor activity in advanced solid tumors. A phase III trial in patients with HER2-low MBC has been initiated.