Triple-Negative Breast Cancer (TNBC)
Conditions
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.
Interventions
DRUGESG401
IV infusion on day 1,8, and 15 of each 28 day cycle
Paclitaxel, Nab-paclitaxel, Capecitabine, Eribulin, or Carboplatin
Sponsors
Qilu Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| 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 |
| 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. |
| 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 |
| 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. |
| 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. |
Countries
China
Contacts
Primary ContactXiaoyan Xing, PhD
Backup ContactFei Ma, PhD
Outcome results
None listed