ESG401, a novel Trop2 ADC with SN38 conjugated to a humanized Trop2 mAb via a proprietary stable-cleavable linker at DAR8, is being evaluated in a Phase Ia/Ib ESG401-101 study to assess its efficacy in various subtypes of mBC in China. The results from this trial were presented at the ESMO 2024 conference. 

Phase Ia was a dose-escalation study, while Phase Ib consisted of three parallel cohorts: 

1. Late-stage TNBC cohort with two randomized groups receiving 12 mg/kg and 14 mg/kg

2. Late-stage HR+/HER2- cohort with two randomized groups receiving 12 mg/kg and 16 mg/kg

3. First-line TNBC cohort receiving 16 mg/kg, all dosing on Days 1, 8, and 15 every 28 days.

A total of 141 mBC patients had received at least one dose of ESG401 as of April 29, 2024. Among them, there were 47 late-stage TNBC patients, 65 late-stage HR+/HER2–BC patients, 27 first-line TNBC patients, and 2 HER2+BC patients previously heavily treated with anti-HER2 agents.

Efficacy data for efficacy-evaluable metastatic breast cancer patients by subtypes are presented in the table below:  

The safety profile of ESG401 was similar across different metastatic breast cancer 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. 

Conclusion 

As per DelveInsight, there were approximately 208,400 incident cases of HR+/HER2- breast cancer and 44,600 incident cases of TNBC in the United States, in 2023. 

The presentation of ESG401, a novel Trop2 ADC, in the Phase Ia/Ib study at ESMO 2024 has generated significant attention due to its promising efficacy in various subtypes of metastatic breast cancer. Results demonstrated ESG401 promise and durable therapeutic efficacy in breast cancer. Notably, it demonstrated significant efficacy in first-line TNBC patients. This suggests that ADC drugs may be more effective when used earlier.  

However, the trial has certain limitations, including a small sample size, immature PFS data, and the inclusion of only Asian participants. A Phase III Study of ESG401 as monotherapy as first-line treatment for unresectable recurrent or metastatic TNBC is planned.  

As of now, the only established TROP2-targeting ADC in the market is TRODELVY (sacituzumab govitecan), developed by Gilead Sciences. Approved for metastatic triple-negative breast cancer , it has paved the way for TROP2 ADCs, offering significant survival benefits, especially in heavily pretreated patients. If ESG401 continues to demonstrate strong efficacy in larger trials, it could become a formidable competitor to TRODELVY. Its broad activity across subtypes and manageable safety profile could differentiate it in this challenging market.

Ongoing Phase III trials with anti-TROP-2 ADCs in 1L mTNBC

For more insight into the patient's burden/epidemiology, treatment, and changing market landscape-related advancements, refer to the following reports: 

• Metastatic HR+/HER2− Breast Cancer - Market Insights, Epidemiology, and Market Forecast-2032 
• Triple Negative Breast Cancer (TNBC) - Market Insights, Epidemiology, and Market Forecast-2032.