A Phase III Study of ESG401 for Unresectable Recurrent or Metastatic Triple-Negative Breast Cancer

A Randomized, Open-label, Phase III Study of ESG401 Versus Investigator's Choice Chemotherapy as First-line Treatment in Patients With Unresectable Recurrent or Metastatic Triple-Negative Breast Cancer

The aim of this study is to evaluate the efficacy and safety of ESG401 as first-line treatment in patients with unresectable recurrent or metastatic triple-negative breast cancer.

Study Overview

• Status: Recruiting
• Conditions: Triple-Negative Breast Cancer (TNBC)
• Intervention / Treatment: Drug: ESG401; Drug: Investigator's Choice Chemotherapy

Detailed Description

This is a randomized, open-label, multicenter Phase 3 study to evaluate ESG401 versus Investigator's Choice Chemotherapy (ICC) as first-line treatment in subjects with unresectable recurrent or metastatic triple-negative breast cancer.

• Study Type: Interventional
• Enrollment (Estimated): 504
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Fei Ma, PhD
• Study Contact Backup: Name: Xiaoyan Xing, PhD; Phone Number: +86 21 5855 6098; Email: xingxiaoyan@escugen.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Cancer Institute and Hospital, Chinese Academy of Medical Sciences
    • Contact: Fei Ma, PhD; Phone Number: 8610-8778-8120; Email: drmafei@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Males or females aged ≥ 18 years ;
2. Histologically and/or cytologically confirmed TNBC;
3. De novo metastatic or relapsed ≥ 6 months post completion of treatment with curative intent;
4. No prior systemic anti-cancer therapy for unresectable recurrent or metastatic disease;
5. Participants whose tumours are PD-L1-negative, or Participants whose tumours are PD-L1-positive and have relapsed after prior PD-1/PD-L1 inhibitor therapy for early-stage breast cancer, or comorbidities precluding PD-1/PD-L1 inhibitor therapy;
6. Eligible for the chemotherapy options listed as investigator's choice chemotherapy (paclitaxel, nab-paclitaxel, capecitabine, eribulin, or carboplatin) as assessed by the investigator;
7. At least one measurable lesion per RECIST v1.1;
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 with no worsening within 2 weeks prior to randomization;
9. A life expectancy of at least 12 weeks;
10. Adequate organ and bone marrow function.

Key Exclusion Criteria:

1. Use of any investigational anti-cancer drug within 28 days or 5 half-lives before the first investigational product administration.
2. Toxicities from prior anti-tumor therapy not recovering to ≤ Grade 1.
3. Prior topoisomerase I inhibitor therapy, including antibody-drug conjugate(ADC) therapy, or prior TROP2 targeted therapy.
4. New thromboembolic events, intestinal obstruction, gastrointestinal bleeding or perforation within 6 months.
5. Subjects with symptomatic or untreated CNS metastases, or those requiring ongoing treatment for CNS metastases.
6. Patients with Primary CNS malignancy, or patients with other malignancies within 3 years prior to the first dose.
7. Patients with uncontrollable systemic diseases.
8. Patients with gastrointestinal diseases (such as chronic gastritis, chronic enteritis or gastric ulcers), or with a previous history of severe or chronic diarrhea.
9. Subjects with clinically significant cardiovascular disease.
10. Human Immunodeficiency Virus (HIV) infection.
11. Active hepatitis B or hepatitis C.
12. Known immediate or delayed hypersensitivity reaction to irinotecan or other camptocampin derivatives such as topotecan or to have had grade≥3 gastrointestinal reactions associated with irinotecan, or allergies, or to any investigational drug or excipient ingredient.
13. Pregnant or lactating women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ESG401 for injection; IV infusion on day 1, 8 and15 of each 28 day cycle	Drug: ESG401; IV infusion on day 1,8, and 15 of each 28 day cycle
Active Comparator: Investigator's Choice Chemotherapy; If no prior taxane, or prior taxane in the (neo)adjuvant setting and disease-free interval (DFI) >12 months: paclitaxel or nab-paclitaxel. Note: If subjects are intolerant or contraindicated to receive paclitaxel or albumin-paclitaxel, the investigator may choose other chemotherapy options listed in the study protocol) If prior taxane and DFI ≤ 12 months: capecitabine, eribulin. If known BRCA1/2 mutation: carboplatin	Drug: Investigator's Choice Chemotherapy; Paclitaxel, Nab-paclitaxel, Capecitabine, Eribulin, or Carboplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) assessed by Blinded Independent Central Review (BICR)	Defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on BICR or death due to any cause, whichever occurs first.	Randomization up to approximately 28 months
Overall Survival (OS)	Defined as the time from randomization until the date of death due to any cause.	Randomization up to approximately 41 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events(AEs) and severe adverse events (SAEs)	Incidence and severity of AEs and SAEs (per CTCAE 5.0), and clinically significant abnormal laboratory findings	From signing the ICF up to last dose plus 30 days
Progression-Free Survival (PFS) assessed by Investigator	Defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on investigator or death due to any cause, whichever occurs first.	Randomization up to approximately 28 months
Objective Response Rate (ORR) assessed by Blinded Independent Central Review (BICR)	Defined as the percentage of patients who achieve complete response(CR) or partial response (PR), as assessed by BICR per RECIST 1.1	Randomization up to approximately 28 months
Disease control rate (DCR) assessed by Blinded Independent Central Review (BICR)	Defined as the percentage of patients who achieve CR, PR or stable disease (SD), as assessed by BICR per RECIST 1.1	Randomization up to approximately 28 months
Duration of Response (DoR) assessed by Blinded Independent Central Review (BICR)	Defined as the time from the date of first documented CR or PR until date of documented disease progression per RECIST 1.1, as assessed by BICR or death due to any cause, whichever occurs first.	Randomization up to approximately 28 months
Time to Response (TTR) assessed by Blinded Independent Central Review (BICR)	Defined as the time from the date of randomization until the first documentation of CR or PR as assessed by BICR per RECIST 1.1.	Randomization up to approximately 28 months
Objective Response Rate (ORR) assessed by Investigator	Defined as the percentage of patients who achieve complete response(CR) or partial response (PR), as assessed by investigator per RECIST 1.1	Randomization up to approximately 28 months
Disease control rate (DCR) assessed by Investigator	Defined as the percentage of patients who achieve CR, PR or stable disease (SD), as assessed by investigator per RECIST 1.1	Randomization up to approximately 28 months
Duration of Response (DoR) assessed by Investigator	Defined as the time from the date of first documented CR or PR until date of documented disease progression per RECIST 1.1, as assessed by investigator or death due to any cause, whichever occurs first.	Randomization up to approximately 28 months
Time to Response (TTR) assessed by Investigator	Defined as the time from the date of randomization until the first documentation of CR or PR as assessed by investigator per RECIST 1.1.	Randomization up to approximately 28 months
Quality of life evaluated using the NCC-BC-A scale	To assess the impact of ESG401 on disease related symptoms and quality of life of patients using the NCC-BC-A scale	Randomization up to approximately 28 months
Clearance	Mean population clearance will be derived from pooled data of drug concentrations. Covariates of influence on drug clearance will be incorporated within a population pharmacokinetic model.	Randomization up to approximately 28 months
Volume of distribution	Mean population volume of distribution will be derived from pooled data of drug concentrations. Covariates of influence on volume of distribution will be incorporated within a population pharmacokinetic model.	Randomization up to approximately 28 months
Anti-drug Antibodies	Incidence of anti-drug antibodies.	Randomization up to approximately 28 months

Collaborators and Investigators

• Sponsor: Qilu Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Fei Ma, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: December 10, 2024
• First Submitted That Met QC Criteria: December 10, 2024
• First Posted (Actual): December 13, 2024

Study Record Updates

• Last Update Posted (Estimated): September 23, 2025
• Last Update Submitted That Met QC Criteria: September 18, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Skin and Connective Tissue Diseases; Triple Negative Breast Neoplasms
• Other Study ID Numbers: ESG401-302

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No