A Phase 3, Open-label, Randomised Study of FDA018-ADC Versus Investigator's Choice of Chemotherapy in Patients Who Recurred During or After Taxane Therapy in Locally Advanced or Metastatic Triple-negative Breast Cancer

Official 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.

Eligibility Requirements

• Minimum Age: 18 Years
• Maximum Age: 75 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 350 participants

Study Arms

• FDA018-ADC (EXPERIMENTAL)
  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.
• Investigator's Choice of Chemotherapy (ICC) (ACTIVE_COMPARATOR)
  Participants will receive ICC (ie, eribulin, capecitabine, gemcitabine, or vinorelbine), administered as a single-agent regimen that is selected by the investigator before participant randomization. Participants will continue treatment until disease progression, unacceptable toxicity or death.

Interventions

• DRUG: FDA018-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.
• DRUG: Eribulin — 1.4mg/m\^2, IV (in the vein) on day 1 and Day 8 of each 21 day cycle
• DRUG: Capecitabine — 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
• DRUG: Gemcitabine — 800 to 1200 mg/m\^2 will be administered IV on day 1 and Day 8 of each 21 day cycle
• DRUG: Vinorelbine — 25 mg/m\^2, IV (in the vein) on day 1 and Day 8 of each 21 day cycle

Primary Outcomes

• Progression-free survival (PFS) (up to 24 months)
• Overall Survival (OS) (up to 24 months)

Secondary Outcomes

• Progression-Free Survival (PFS) by Investigator assessment (up to 24 months)
• Objective Response Rate (ORR) (up to 24 months)
• Duration of Response Duration of Response (DoR) (up to 24 months)
• Disease Control Rate (DCR) (up to 24 months)
• Incidence of Treatment-Emergent Adverse Events (up to 24 months)

Eligibility Criteria

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.

Trial Locations

• Fudan University Shanghai Cancer Center, Shanghai, Shanghai Municipality, China

Study Officials

• Jian Zhang — PRINCIPAL_INVESTIGATOR
  Fudan University

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