349MO - Results from a phase Ia/Ib Study of ESG401, a novel Trop2 antibody-drug conjugate, in patients with different subtypes of metastatic breast cancer

Background

ESG401, a novel Trop2 ADC with SN38 conjugated to a humanized Trop2 mAb via a proprietary stable-cleavable linker at DAR8, was administrated to assess its efficacy in various subtypes of mBC.

Methods

This open-label, multiple-dose phase Ia/ Ib trial enrolled pts with metastatic solid tumors. Phase Ia was a dose-escalation study, while phase Ib consisted of three parallel cohorts: (1) a late-stage TNBC cohort with two randomized groups receiving 12 mg/kg and 14 mg/kg, (2) a late-stage HR+/HER2- cohort with two randomized groups receiving 12 mg/kg and 16 mg/kg, and (3) a first-line TNBC cohort receiving 16 mg/kg, all dosing on Days 1, 8, and 15 every 28 days.

Results

A total of 141 mBC pts (median age 52 yrs) had received at least one dose of ESG401 as of Apr 29, 2024. Among them, there were 47 late-stage TNBC pts (median prior lines: 3; range: 1–12), 65 late-stage HR+/HER2–BC pts (median prior lines: 3; range: 1–10), 27 first-line TNBC pts, and 2 HER2+BC pts previously heavily treated with anti-HER2 agents (prior lines: 3 and 7). Efficacy data for efficacy-evaluable mBC pts by subtypes are presented in the table. The longest durations of ESG401 treatment for pts with late-stage HR+/HER2–BC, TNBC, HER2+BC, and first-line TNBC were 23.1, 18.6, 21.3, and 11.0 months (all still on treatment), respectively. One patient with first-line TNBC achieved a complete response (CR). The safety profile of ESG401 was similar across different mBC subtypes, with the most common grade ≥3 treatment-related adverse events being neutropenia and leukopenia. Safety findings were consistent with the primary analysis, and no new safety signals were identified. Table: 349MO

*: The actual value for these two patients is listed.

Conclusions

ESG401 demonstrates promising and durable therapeutic efficacy in various subtypes of mBC. Despite the limited sample size, there was no significant difference in efficacy observed among the three types of late-line and heavily treated BC patients. 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

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