Triple Negative Breast Cancer
Conditions
Brief summary
This is a Phase III, randomized, open-label, 2-arm, multicentre, international study assessing the efficacy and safety of FDA018-ADC compared with Investigator's Choice Chemotherapy(ICC) in participants with locally recurrent inoperable or metastatic Triple-negative Breast Cancer(TNBC) who are resistant to, or recurring during or after taxane therapy.
Detailed description
The primary objectives of the study are to demonstrate the superiority of FDA018-ADC relative to ICC by assessment of PFS per Blinded Independent Central Review(BICR) and OS in participants with locally recurrent inoperable or metastatic TNBC who are resistant to, or recurring during or after taxane therapy.
Interventions
DRUGFDA018-ADC
Subjects will receive FDA018-ADC 10 mg/kg of body weight via intravenous(IV) infusion on Day1 and 8 of a 21-day cycle in follow-up period until disease progression, unacceptable toxicity or death.
DRUGEribulin
1.4mg/m\^2, IV (in the vein) on day 1 and Day 8 of each 21 day cycle
DRUGCapecitabine
1000 to 1250 mg/m\^2 will be administered in a 21-day cycle, with capecitabine administered orally twice daily for 2 weeks followed by 1-week rest
DRUGGemcitabine
800 to 1200 mg/m\^2 will be administered IV on day 1 and Day 8 of each 21 day cycle
DRUGVinorelbine
25 mg/m\^2, IV (in the vein) on day 1 and Day 8 of each 21 day cycle
Sponsors
Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Patients capable to give written informed consent; 2. Histologically or cytologically confirmed TNBC based on the most recent analyzed biopsy or other pathology specimen. Triple negative is defined as \<1% expression for estrogen receptor (ER) and progesterone receptor (PR) and negative for human epidermal growth factor receptor 2 (HER2) by in-situ hybridization; 3. Prior exposure to a taxane in localized or advanced/metastatic setting, and recurred during or after treatment; 4. Eligible for one of the chemotherapy options listed as ICC (eribulin, capecitabine, gemcitabine, or vinorelbine) as per investigator assessment; 5. Have measurable lesions defined in RECIST v.1.1, those with only skin or bone lesions cannot be included; 6. Expected survival≥3 months; 7. Eastern Cancer Cooperative Group (ECOG) performance status 0-1; 8. Adequate bone marrow, hepatic, and renal function; 9. All acute toxicity of previous anti-tumor treatment or surgery is relieved to baseline severity or NCI CTCAE version 5.0≤1; 10. Subjects could provide tumor tissues or tissue specimens; 11. Patients of child bearing potential must agree to take contraception during the study and for 6 months after the last day of treatment.
Exclusion criteria
1. Patients with other malignancies, except cured basal or squamous cell skin cancer or in situ cancer of cervix; and patients with other malignancies must have a tumor-free period of at least 5 years; 2. Have central nervous system metastasis with clinical symptoms; 3. Have history of clinical significant active chronic obstructive pulmonary disease, or other moderate-to-severe chronic respiratory illness present within 6 months prior to the first dose; 4. Suffering from active chronic inflammatory bowel disease (ulcerative colitis, Crohn disease), and history of intestinal obstruction, or Gl perforation; 5. Patients with Gilbert's disease or heterozygous for the UGT1A1\*28 allele; 6. Participants known to be human immunodeficiency (HIV) positive, hepatitis B positive, or hepatitis C positive; 7. Patients who have received prior TROP-2-targeted therapy; 8. Patients who have received prior topoisomerase I inhibitor contained therapy; 9. Received other anti-tumor treatments (including chemotherapy, radiotherapy, targeted therapy, immunotherapy, experimental treatment and so on) within 4 weeks prior to the first dose; 10. Patients who have received live vaccines within 4 weeks prior to the first dose; 11. Patients who had undergone major surgery or severe trauma within 4 weeks prior to the first dose; 12. Patients who had undergone systemic high-dose steroids within 2 weeks prior to the first dose; 13. Patients have history of psychotropic drug abuse, alcohol or drug abuse; 14. Women who are pregnant or lactating; 15. Other circumstances that is deemed not appropriate for the study by investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | up to 24 months | OS is defined as the time from randomisation until the date of death due to any cause. |
| Progression-free survival (PFS) | up to 24 months | PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) by Investigator assessment | up to 24 months | PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by the investigator, or death due to any cause |
| Objective Response Rate (ORR) | up to 24 months | ORR is defined as the proportion of participants who have a confirmed CR or PR, as determined by BICR/investigator assessment, per RECIST 1.1. |
| Duration of Response Duration of Response (DoR) | up to 24 months | DoR is defined as the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1, as assessed by BICR/investigator assessment or death due to any cause. |
| Disease Control Rate (DCR) | up to 24 months | DCR is defined as the proportion of patients who have achieved complete response，partial response and stable disease assessed by BICR/investigator according to RECIST v 1.1 |
| Incidence of Treatment-Emergent Adverse Events | up to 24 months | Incidence and severity of AEs and SAEs (graded by CTCAE version 5.0). |
| Immunogenicity of FDA018-ADC | up to 24 months | Presence of ADAs for FDA018-ADC |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORJian Zhang
Fudan University
Outcome results
None listed