| Eligibility |
Key Inclusion Criteria:
1. Male or female Chinese, 18 years of age or older providing written informed consent.
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
3. Histologically or cytologically confirmed Triple-negative Breast Cancer (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 Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) in
accordance with Response Evaluation Criteria in Solid Tumors (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 individuals 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 individuals must have been previously treated with a taxane regardless of disease
stage (adjuvant, neoadjuvant or advanced) when it was given. Individuals 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 mm^3, platelets >
100,000 per mm^3.
- creatinine clearance of > 60 ml/min calculated using Cockcroft-Gault equation.
- bilirubin = 1.5 Upper Limit of Normal (ULN), aspartate amino transferase and
alanine amino transferase = 2.5 × ULN or = 5 × ULN 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. Individuals 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. Individuals must have at least a 3-month life expectancy.
Key Exclusion Criteria:
1. Previous treatment with topoisomerase 1 inhibitors as a free form or as other
formulations.
2. Individuals with a history of or current central nervous system (CNS) metastases. A
scan to confirm the absence of brain metastases is not required. Individuals 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. Individuals with Gilbert's disease.
4. Individuals with non-melanoma skin cancer or carcinoma in situ of the cervix are
eligible, while individuals with other prior malignancies must have had at least a
3-year disease-free interval.
5. Individuals known to be human immunodeficiency virus positive.
6. Individuals with active hepatitis B virus (HBV), or hepatitis C virus (HCV) infection.
In individuals 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
individual 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. Individuals with active chronic inflammatory bowel disease (ulcerative colitis, Crohn
disease) and individuals with a history of bowel obstruction or gastrointestinal (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. Individuals 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. Females who are pregnant or lactating.
17. Females of childbearing potential or fertile males unwilling to use highly effective*
contraception during study and up to 6 months after treatment discontinuation in
females of childbearing potential and 3 months in males post last Investigational
Medicinal Product (IMP) administration.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
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