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

Phase 3

Not yet recruiting

• Conditions: Triple-Negative Breast Cancer (TNBC)
• Interventions: Drug: ESG401; Drug: Investigator's Choice Chemotherapy

• Registration Number: NCT06732323
• Lead Sponsor: Shanghai Escugen Biotechnology Co., Ltd

Brief Summary

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.

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 Timeline

• Status Verified: 2024-12
• Study First Submitted: 2024-12-10
• Study First Submitted QC: 2024-12-10
• Last Update Submitted: 2024-12-10
• Study First Posted: 2024-12-13
• Last Update Posted: 2024-12-13
• Study Start: 2025-02
• Primary Completion: 2027-06
• Study Completion: 2028-07

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 504

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ESG401 for injection	ESG401	IV infusion on day 1, 8 and15 of each 28 day cycle
Investigator's Choice Chemotherapy	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

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS) assessed by Blinded Independent Central Review (BICR)	Randomization up to approximately 28 months	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.
Overall Survival (OS)	Randomization up to approximately 41 months	Defined as the time from randomization until the date of death due to any cause.

Secondary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS) assessed by Investigator	Randomization up to approximately 28 months	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.
Objective Response Rate (ORR) assessed by Blinded Independent Central Review (BICR)	Randomization up to approximately 28 months	Defined as the percentage of patients who achieve complete response(CR) or partial response (PR), as assessed by BICR per RECIST 1.1
Disease control rate (DCR) assessed by Blinded Independent Central Review (BICR)	Randomization up to approximately 28 months	Defined as the percentage of patients who achieve CR, PR or stable disease (SD), as assessed by BICR per RECIST 1.1
Quality of life evaluated using the NCC-BC-A scale	Randomization up to approximately 28 months	To assess the impact of ESG401 on disease related symptoms and quality of life of patients using the NCC-BC-A scale
Adverse events(AEs) and severe adverse events (SAEs)	From signing the ICF up to last dose plus 30 days	Incidence and severity of AEs and SAEs (per CTCAE 5.0), and clinically significant abnormal laboratory findings
Duration of Response (DoR) assessed by Blinded Independent Central Review (BICR)	Randomization up to approximately 28 months	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.
Clearance	Randomization up to approximately 28 months	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.
Time to Response (TTR) assessed by Blinded Independent Central Review (BICR)	Randomization up to approximately 28 months	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.
Objective Response Rate (ORR) assessed by Investigator	Randomization up to approximately 28 months	Defined as the percentage of patients who achieve complete response(CR) or partial response (PR), as assessed by investigator per RECIST 1.1
Disease control rate (DCR) assessed by Investigator	Randomization up to approximately 28 months	Defined as the percentage of patients who achieve CR, PR or stable disease (SD), as assessed by investigator per RECIST 1.1
Duration of Response (DoR) assessed by Investigator	Randomization up to approximately 28 months	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.
Time to Response (TTR) assessed by Investigator	Randomization up to approximately 28 months	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.
Volume of distribution	Randomization up to approximately 28 months	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.
Anti-drug Antibodies	Randomization up to approximately 28 months	Incidence of anti-drug antibodies.

Trial Locations

Locations (1)

Cancer Institute and Hospital, Chinese Academy of Medical Sciences; 🇨🇳 Beijing, China