This is a Phase IIb, single arm, multicenter study of sacituzumab govitecan in locally
advanced or metastatic TNBC patients who are refractory or relapsing after at least 2 prior
standard chemotherapy regimens for unresectable, locally advanced or metastatic breast
cancer, and these regimens will qualify regardless of triple-negative status at the time they
were given. The primary endpoint of the trial will be the ORR per RECIST v 1.1 by Independent
Review Committee (IRC) in all treated patients.
Patients will be treated until progression requiring discontinuation of further treatment,
unacceptable toxicity, study withdrawal, or death, whichever comes first. Tumor response and
progression will be assessed using RECIST v 1.1 and assessment by Investigator at the trial
center will be sufficient for decisions on continuation of treatment. An independent analysis
of response will also be performed by IRC, but this will not be used to make treatment
decisions. All patients will visit the Investigator at regular intervals for assessment of
safety parameters and AEs.
Inclusion Criteria:
1. Male or female Chinese, 18 years of age or older providing written informed consent.
2. ECOG performance status of 0 or 1.
3. Histologically or cytologically confirmed TNBC.
4. Refractory to or relapsed after at least 2 prior standard of care chemotherapy
regimens for unresectable, locally advanced or metastatic breast cancer.
5. Measurable disease by CT or MRI in accordance with RECIST v 1.1.
6. Availability of archival tumor tissue or newly acquired biopsy (FFPE block or a
minimum of number 10 unstaining tumor slides, recommended from recurrent or metastatic
sites).
7. For patients with a documented germ-line BRCA1/BRCA2 mutation who received an approved
PARP inhibitor, the PARP inhibitor can be used to meet the criteria for one of 2 prior
standard of care chemotherapies.
8. All patients must have been previously treated with a taxane regardless of disease
stage (adjuvant, neoadjuvant or advanced) when it was given. Patients who have
contraindications or are intolerant to taxanes are eligible provided that they
received at least 1 cycle of a taxane and showed contraindications or intolerance
during or at the end of that cycle.
9. Adequate bone marrow, hepatic and renal function, defined as:
- hemoglobin > 9 g/dL, absolute neutrophil count > 1,500 per mm3, platelets >
100,000 per mm3.
- creatinine clearance of > 60 ml/min calculated using Cockcroft-Gault equation.
- bilirubin ≤ 1.5 IULN, aspartate amino transferase and alanine amino transferase ≤
2.5 × IULN or ≤ 5 × IULN if known liver metastases and serum albumin ≥ 3 g/dL.
10. Recovered from all prior treatment-related toxicities to Grade 1 or less by National
Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE
v 5.0) (except alopecia or peripheral neuropathy that may be Grade 2 or less).
11. Patients must have completed all prior cancer treatments at least 2 weeks prior to the
first dose including chemotherapy (includes also endocrine treatment), radiotherapy
and major surgery. Prior antibody treatment for cancer must have been completed at
least 3 weeks prior to the first dose.
12. Patients must have at least a 3-month life expectancy.
Exclusion Criteria:
1. Previous treatment with topoisomerase 1 inhibitors as a free form or as other
formulations.
2. Patients with a history of or current central nervous system (CNS) metastases. A scan
to confirm the absence of brain metastases is not required. Patients with unknown CNS
metastatic status and any clinical signs indicative of CNS metastases are eligible if
CNS metastases are excluded using CT and/or MRI scans.
3. Patients with Gilbert's disease.
4. Patients with non-melanoma skin cancer or carcinoma in situ of the cervix are
eligible, while patients with other prior malignancies must have had at least a 3-year
disease-free interval.
5. Patients known to be human immunodeficiency virus positive.
6. Patients with active hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. In
patients with a history of HBV, hepatitis B core antibody (HBcAb) testing is required
and if positive, then HBV DNA testing will be performed and if positive the patient
will be excluded.
7. Known history of unstable angina, myocardial infarction (MI), or chronic heart failure
present within 6 months of first dose or clinically significant cardiac arrhythmia
(other than stable atrial fibrillation) requiring anti-arrhythmia therapy or left
ventricular ejection fraction < 50%.
8. Known history of clinically significant active chronic obstructive pulmonary disease,
or other moderate-to-severe chronic respiratory illness present within 6 months of the
first dose.
9. Infection requiring systematic antibiotic use within 1 week of the first dose.
10. Patients with active chronic inflammatory bowel disease (ulcerative colitis, Crohn
disease) and patients with a history of bowel obstruction or GI perforation.
11. High dose systemic corticosteroids within 2 weeks prior to the first dose (however,
low dose corticosteroids ≤ 10 mg prednisone or equivalent daily are permitted provided
the dose is stable for 4 weeks).
12. Scheduled surgery during the study, other than minor surgery which would not delay
study treatment.
13. Patients who have received a live vaccine within 30 days of first dose.
14. Rapid deterioration during Screening prior to the first dose, eg, significant change
in performance status, unstable pain symptoms requiring modifications in analgesic
management.
15. Other concurrent medical or psychiatric conditions that, in the Investigator's
opinion, may be likely to confound study interpretation or prevent completion of study
procedures and follow-up examinations.
16. Women who are pregnant or lactating.
17. Women of childbearing potential or fertile men unwilling to use highly effective*
contraception during study and up to 6 months after treatment discontinuation in women
of childbearing potential and 3 months in males post last IMP administration.
