Recently, the preclinical and Phase I clinical results of TQB2102 (a HER2 bispecific-bispecific ADC), a first-in-class (FIC) new drug independently developed by Chia Tai Tianqing, a core enterprise of Sino Biopharmaceutical (1177.HK), for the treatment of advanced solid tumors, were published online in Annals of Oncology (impact factor 65.4), the flagship journal of the European Society for Medical Oncology (ESMO). This study, led by the team of Academician Xu Ruihua and Professor Wang Shusen from Sun Yat-sen University Cancer Center, for the first time systematically released the efficacy and safety data of TQB2102 from human clinical studies, and simultaneously disclosed its preclinical research results, confirming the differentiated characteristics of TQB2102 as a bispecific HER2 ADC. 

Antibody-drug conjugates (ADCs), a hot area in current tumor drug R&D, link monoclonal antibodies to cytotoxic drugs via a linker to achieve precise delivery of drugs to tumor cells, earning them the nickname "magic bullets". Although ADCs have made significant progress in the clinic, issues such as tumor heterogeneity, drug resistance, and interstitial pneumonia remain bottlenecks in their development, necessitating breakthroughs from a new generation of innovative ADC drugs. 

Preclinical Research: Innovative Design Achieves High Efficacy and Low Toxicity

As a new-generation HER2 bispecific-targeting ADC, TQB2102 optimizes the balance between efficacy and safety through structural innovation. The drug is composed of a recombinant humanized anti-HER2 bispecific antibody (targeting the HER2 ECD II/IV domains) conjugated to a topoisomerase I (TOP1) inhibitor via an enzyme-cleavable linker, with a drug-to-antibody ratio (DAR) of approximately 6.0. Its unique design significantly enhances the antibody's specific binding affinity and internalization efficiency, promoting more efficient entry of the drug into tumor cells to exert its killing effect, while retaining a bystander effect, showing good efficacy even in patients with HER2 low-expressing tumors. 

Preclinical study data confirmed that TQB2102 has potent inhibitory activity against various tumor cell lines and cell-derived xenograft (CDX) models. Notably, at the same dosage, TQB2102 achieved a higher tumor inhibition rate in gastric cancer, breast cancer, and colorectal cancer CDX models compared to two other HER2 ADCs. Furthermore, TQB2102 was well-tolerated in non-human primates, with no pulmonary toxicity observed. 

Clinical Validation: Phase I Study Demonstrates Clinical Benefit and Safety

The Phase I clinical study enrolled a total of 195 patients with advanced solid tumors who had undergone multiple lines of treatment, covering breast cancer, digestive tumors (such as intestinal cancer and gastric cancer), and other HER2-expressing tumor types. The study included dose-escalation and dose-expansion phases. 

In terms of clinical benefit, for patients with HER2-positive breast cancer, colorectal cancer, and gastric/gastroesophageal junction adenocarcinoma, the objective response rate (ORR) reached 52.4%, 38.7%, and 40.0%, respectively. Notably, for patients with brain metastasis, the ORR for HER2-positive breast cancer and HER2 low breast cancer patients was as high as 70.0% and 50.0%, respectively. In terms of safety, no dose-limiting toxicity (DLT) was observed in any patient, and the overall safety profile was good and manageable. The recommended Phase II dose is 6.0 mg/kg or 7.5 mg/kg every 3 weeks. The most common ≥Grade 3 treatment-related adverse event (TRAE) was neutropenia (23.2%), and the incidence of interstitial pneumonia was only 0.5%. 

These results indicate that TQB2102 has a good safety window and anti-tumor activity across the HER2 expression spectrum, supporting its further development in various advanced solid tumors. Currently, TQB2102 is advancing in multiple Phase III clinical studies, covering chemotherapy-naive advanced HER2 low breast cancer, advanced HER2-positive breast cancer after failure of anti-HER2 therapy, neoadjuvant therapy for HER2-positive breast cancer, first-line treatment for HER2-positive advanced breast cancer, later-line treatment for HER2-positive advanced biliary tract cancer, and HER2-positive advanced colorectal cancer after failure of treatment with oxaliplatin, irinotecan, and fluorouracil-based drugs. We look forward to the subsequent research results of TQB2102, hoping it will benefit the broad population of tumor patients soon. 

Declaration:

1. This press release is intended to facilitate the communication and exchange of medical information and is for reference by healthcare professionals only. It is not for advertising purposes. 

2. The company does not recommend any drugs and/or indications. 

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Forward-Looking Statements:

This press release contains certain forward-looking statements, including statements regarding the clinical development plan, expectations of clinical benefits and advantages, commercialization outlook, the likelihood of clinical benefit for patients, and potential commercial opportunities for [TQB2102]. Words such as "expect", "believe", "continue", "may", "estimate", "hope", "intend", "plan", "potential", "predict", "project", "should", "will", "propose", and similar expressions are intended to identify forward-looking statements, but not all forward-looking statements contain these identifying words. These forward-looking statements are predictions or expectations made by the company based on currently available data and information, and actual results may differ materially from these forward-looking statements due to uncertainties or risks such as policy, R&D, market, and regulatory factors. Current or potential investors are advised to carefully consider the potential risks and should not place undue reliance on the forward-looking statements in this press release, which contain information only as of the date of this press release. Unless required by law, the company undertakes no obligation to update or revise any forward-looking statements in this press release as a result of new information, future events, or other circumstances. 

Source: Sun Yat-sen University Cancer Center Subscription Account