Preclinical characterization and phase I results of TQB2102, a first-in-class HER2 biparatopic antibody-drug conjugate, in patients with advanced solid tumors

  • Ann Oncol. 2026 May 15:S0923-7534(26)00187-0. doi: 10.1016/j.annonc.2026.05.003.
D Y Ruan  1 ,  S Y Lin  2 ,  J J Huang  3 ,  Y H Li  3 ,  N Li  4 ,  X J Qu  5 ,  X B Du  6 ,  Y M Yin  7 ,  Z Y Yuan  3 ,  Y X Shi  3 ,  F Xu  3 ,  X An  3 ,  R X Hong  3 ,  W Xia  3 ,  C Xue  3 ,  X W Bi  3 ,  K K Jiang  3 ,  Q F Zheng  3 ,  Y Q Zhang  8 ,  J J Peng  9 ,  Z Y Liu  10 ,  H H Xiong  11 ,  A L Suo  12 ,  R B Lin  13 ,  S Zhang  14 ,  S N Tang  15 ,  Y Yu  16 ,  X Li  15 ,  X Wang  15 ,  X Tian  17 ,  P Lv  17 ,  C Shen  17 ,  L G Lou  18 ,  L Wang  18 ,  Z P Zhang  19 ,  T J Xu  19 ,  T X Chen  19 ,  S S Wang  20 ,  R H Xu  21
Affiliations
  • 1. Department of Clinical Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China; Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, China.
  • 2. Department of Clinical Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China.
  • 3. Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China.
  • 4. Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
  • 5. Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.
  • 6. Departmant of Oncology, Nuclear Medicine Laboratory of Mianyang Central Hospital, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China.
  • 7. Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  • 8. Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
  • 9. Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
  • 10. Department of Gastroenterology and Urology, Hunan Cancer Hospital, Changsha, China.
  • 11. Department of Oncology, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 12. Departmant of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • 13. Department of Gastrointestinal Oncology, Fujian Cancer Hospital, Fuzhou, China.
  • 14. Department of Biological Treatment, West China Hospital, Sichuan University, Chengdu, China.
  • 15. Department of Clinical Research Center, Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Nanjing, China.
  • 16. Department of Clinical Biostatistics, Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Nanjing, China.
  • 17. Preclinical Development Department, Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Nanjing, China.
  • 18. Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • 19. Innovative Biopharmaceutical Institute, Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Nanjing, China.
  • 20. Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China. Electronic address: [email protected].
  • 21. Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, China; Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China. Electronic address: [email protected].
PMID: 42142622 DOI: 10.1016/j.annonc.2026.05.003
Abstract

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.

Keywords
HER2; TQB2102; advanced solid tumors; biparatopic antibody-drug conjugate; breast cancer.
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