TQB2102 Shows Strong Activity Across HER2-Expressing Tumors : Ann Oncol | May 2026

Introduction

Antibody-Drug Conjugate development has rapidly transformed treatment paradigms for HER2-expressing malignancies. However, resistance, heterogeneous HER2 expression and toxicity remain major limitations of currently available HER2-targeted therapies. TQB2102 is a next-generation biparatopic HER2 antibody-drug conjugate simultaneously targeting extracellular domain 2 and extracellular domain 4 of HER2 while delivering a topoisomerase I inhibitor payload through an enzyme-cleavable linker.

Problem Statement

Current HER2-directed ADCs demonstrate variable activity across tumor types and limited efficacy in HER2-low disease or brain metastases. Novel HER2-targeting strategies capable of improving receptor binding, internalization and payload delivery while maintaining manageable toxicity profiles are needed.

Summary

This first-in-human multicenter phase I trial evaluated TQB2102 in 195 patients with advanced solid tumors, including metastatic breast cancer, colorectal cancer and gastric/gastroesophageal junction adenocarcinoma. The study incorporated both dose-escalation and dose-expansion cohorts using administration every three weeks.

TQB2102 demonstrated a favorable safety profile across all dose levels. No dose-limiting toxicities occurred, the maximum tolerated dose was not reached and recommended phase II doses were established at 6.0 mg/kg and 7.5 mg/kg. The most frequent grade ≥3 toxicities were hematologic, including neutropenia, leukopenia and anemia. Importantly, only one patient developed treatment-related interstitial lung disease, a particularly notable finding given ILD concerns with several currently approved HER2 ADCs.

Preliminary antitumor efficacy was highly encouraging across multiple HER2-expressing tumor types. Objective response rates exceeded 50% in metastatic breast cancer and approached 40% in both colorectal cancer and gastric/gastroesophageal junction adenocarcinoma. Particularly striking activity was observed in HER2-low metastatic breast cancer, where response rates remained robust despite lower receptor expression. These findings reinforce the possibility that biparatopic HER2 targeting may enhance receptor clustering, internalization and intracellular payload delivery beyond conventional monospecific HER2 ADCs.

The activity observed in patients with brain metastases was especially noteworthy. Objective response rates reached 70% in HER2-positive breast cancer brain metastases and 50% even among HER2-low cases, suggesting substantial intracranial activity. Given the major unmet need for effective CNS-penetrant HER2 therapies, these findings may have important implications for future metastatic breast cancer management strategies.

Mechanistically, biparatopic targeting of HER2 ECD2 and ECD4 likely improves receptor engagement and enhances lysosomal trafficking compared with traditional single-epitope HER2 antibodies. Combined with a membrane-permeable topoisomerase I inhibitor payload, this design may additionally promote bystander killing within heterogeneous HER2-expressing tumors, potentially explaining activity in HER2-low disease settings.

Overall, this first-in-class phase I study positions TQB2102 as a highly promising next-generation HER2 ADC with encouraging efficacy across multiple advanced solid tumors, including HER2-low disease and CNS metastases. The manageable toxicity profile and broad antitumor activity support ongoing phase III development, particularly in HER2-low metastatic breast cancer.