344MO - ESG401, a novel Trop2 antibody-drug conjugate (ADC), and its efficacy evidence in HER2-negative metastatic breast cancer with brain metastases

Background

Brain metastases (BMs) in HER2-negative metastatic breast cancer (mBC) represent a significant unmet medical need. ESG401, a novel Trop2 ADC with SN38 conjugated to a humanized Trop2 mAb via a proprietary stable-cleavable linker at DAR8, is previously reported to have promising clinical efficacy against BC. ESG401 has been shown to suppress BMs in preclinical models, prompting to validation of its efficacy for BM in clinical trials.

Methods

In the Phase Ia/b trial, HER2-negative mBC patients (pts) with treated/stable or new BM not requiring treatment at enrollment were eligible. Efficacy was assessed using RECIST 1.1 criteria for both systemic and BM lesions. All HER2- brain metastatic pts within the study were included in this analysis, regardless of hormone receptor status or prior treatment lines.

Results

A total of 134 HER2- mBC pts were enrolled, with 20 (15%) having BMs at baseline. As of Mar 20, 2024, 16 pts had efficacy-evaluable BMs, including 9 heavily pretreated TNBC (median prior lines of therapy: 5; range: 2–10), 5 HR+/HER2-BC (median prior lines of therapy: 4; range: 2–5) in the metastatic setting, and 2 first-line TNBC. The dosing regimens included 6 pts treated at 12 mg/kg, 4 pts at 14 mg/kg, and 6 pts at 16 mg/kg on days 1, 8, and 15 in a 28-day cycle, respectively. Among these 16 pts with BMs, two achieved a complete intracranial response (IC-CR), four had a partial intracranial response, and six had stable diseases as the best intracranial response. The detailed efficacy data are presented in the table. The longest duration of ESG401 treatment for one patient reached 17.7 months (still on treatment). The safety profile of ESG401 was similar in patients with and without BMs. Table: 344MO

Conclusions

ESG401 demonstrates encouraging therapeutic efficacy in both heavily pretreated and first-line HER2-negative mBC-BMs pts, with responses in brain metastatic and systemic lesions being consistent. These findings warrant further clinical evaluation.

Clinical trial identification

NCT04892342.

Editorial acknowledgement

Legal entity responsible for the study

Shanghai Escugen Biotechnology Co., Ltd.

Funding

Shanghai Escugen Biotechnology Co., Ltd.

Disclosure

Q. Zhou: Financial Interests, Personal, Full or part-time Employment: Shanghai Escugen Biotechnology Co., Ltd. All other authors have declared no conflicts of interest.