A Phase III Study of ESG401 for Locally Advanced or Metastatic HR+/HER2- Breast Cancer

A Open-label, Randomized, Multicenter Phase III Study of ESG401 Versus Investigator's Choice Chemotherapy in Patients With Locally Advanced or Metastatic HR+/HER2- Breast Cancer Who Had Failed at Least One Line of Chemotherapy

The aim of this study is to evaluate the efficacy and safety of ESG401 in patients with unresectable locally advanced or metastatic HR+/HER2- breast cancer.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: ESG401; Drug: Eribulin, capecitabine, gemcitabine or vinorelbine (Treatment of Physician's Choice)

Detailed Description

This is a open-label, randomized, multicenter Phase 3 study to evaluate ESG401 versus Treatment of Physician's Choice (TPC) in subjects with unresectable locally advanced or metastatic HR+/HER2- breast cancer who had failed at least one line of systemic chemotherapy.

• Study Type: Interventional
• Enrollment (Estimated): 378
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yong Yuan, Master Degree; Phone Number: +86 13820384005; Email: yong3.yuan@qilu-pharma.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Recruiting
      • Cancer Hospital Chinese Academy of Medical Sciences
      • Contact: Fei Ma, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Individuals able to understand and give written informed consent.
• Males or females aged ≥ 18 years ;
• Histologically and/or cytologically confirmed HR+/HER2- breast cancer who had failed at least one line of systemic chemotherapy in metastatic settings;
• Patients who are eligible for a chemotherapy regimen in the control group;
• Patients with at least one measurable lesion per RECIST 1.1 criteria;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1;
• Expected survival ≥ 12 weeks;
• Patients with adequate organ and bone marrow function;
• Female patients of childbearing potential and male patients with partners of childbearing potential who use effective medical contraception from the time of signing the informed consent form until 180 days after the last dose.

Exclusion Criteria:

• Received chemotherapy, targeted therapy, immunotherapy, interventional therapy or other systemic anti-cancer therapie within 4 weeks before the first investigational product administration;
• Toxicities from prior anti-tumor therapy not recovering to ≤ Grade 1;
• Received major surgeries 4 weeks prior to the first dose of study treatment or planned to receive major surgeries during the study ;
• Prior topoisomerase I inhibitor therapy, including antibody-drugconjugate(ADC) therapy, or prior TROP2 targeted therapy, or use of any investigational anti-cancer drug within 28 days or 5 half-lives before the first investigational product administration;
• New thromboembolic events, intestinal obstruction, gastrointestinal bleeding or perforation within 6 months;
• Uncontrolled systemic bacterial, viral or fungal infections;
• Subjects with symptomatic or untreated CNS metastases, or those requiring ongoing treatment for CNS metastases;
• Patients with Primary CNS malignancy；or patients with other malignancies within 3 years prior to the first dose;
• Patients with uncontrollable systemic diseases;
• Patients with gastrointestinal diseases (such as chronic gastritis, chronic enteritis or gastric ulcers), or with a previous history of severe or chronic diarrhea;
• Subjects with clinically significant cardiovascular disease;
• Human Immunodeficiency Virus (HIV) infection;
• Active hepatitis B or hepatitis C;
• 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;
• 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: Treatment of Physician's Choice; Eribulin 1.4 mg/m2, IV infusion on day 1 and 8 of each 21 day cycle Capecitabine 1000 or 1250 mg/m2, po, from day 1 to 14 of each 21 day cycle Vinorelbine 25 mg/m2, IV infusion on day 1 and 8 of each 21 day cycle Gemcitabine 1000 mg/m2, IV infusion on day 1,8 and 15 of each 28day cycle	Drug: Eribulin, capecitabine, gemcitabine or vinorelbine (Treatment of Physician's Choice); Eribulin, capecitabine, gemcitabine or vinorelbine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS) assessed by IRC per RECIST 1.1	PFS was defined as the time from randomization to PD or death, whichever occurs first.	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS) assessed by the investigators per RECIST V 1.1	PFS was defined as the time from randomization to PD or death, whichever occurs first.	Up to 24 months
Overall Survival (OS)	OS was defined as the time from randomization to death.	Up to 24 months
Objective Response Rate (ORR)	ORR was defined as the proportion of of patients with a CR and PR assessed by IRC and investigators per RECIST v 1.1	Up to 24 months
Clinical Benefit Rate (CBR)	CBR was defined as the proportion of patients with a CR or PR or with SD at Week 24 assessed by IRC and investigators per RECIST v 1.1	Up to 24 months
Duration of Response (DoR)	From the date that response criteria are first met to the first occurrence of PD as determined by BIRC and investigators per RECIST v1.1 or death from any cause, whichever occurs first.	Up to 24 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	Up to 24 months
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
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.	Up to 24 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.	Up to 24 months
ADA	Incidence of anti-drug antibodies	Up to 24 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): July 31, 2028

Study Registration Dates

• First Submitted: April 22, 2024
• First Submitted That Met QC Criteria: April 24, 2024
• First Posted (Actual): April 25, 2024

Study Record Updates

• Last Update Posted (Actual): June 19, 2025
• Last Update Submitted That Met QC Criteria: June 17, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Capecitabine; Vinorelbine; Gemcitabine
• Other Study ID Numbers: ESG401-301

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