Study of Eryaspase in Combination With Chemotherapy Versus Chemotherapy Alone as 1st Line Treatment of TNBC (TRYbeCA-2)

Inclusion Criteria:

1. Female or male, 18 years of age or older.
2. Histologically confirmed diagnosis of invasive breast cancer.
3. Metastatic or locally recurrent inoperable breast cancer not previously treated with chemotherapy.

4. Diagnosis of triple negative breast cancer, defined as the absence of expression of the following receptors in the primary and/or metastatic tumor tissue:

   • HER2 protein over-expression and/or gene amplification, defined as:
   • Estrogen receptor (ER), defined as <1% staining by IHC (2).
   • AND progesterone receptors (PgR), defined as <1% staining by IHC.
5. Measurable lesion(s) per RECIST 1.1.
6. Available archival or fresh tumor tissue.
7. Adequate performance status (PS) score.
8. Life expectancy of >12 weeks according to the Investigator's clinical judgment.
9. Females of childbearing potential must have a negative pregnancy test at screening and an additional pregnancy test prior to first dose. Females of childbearing potential must agree to use a highly effective method of contraception during treatment and for at least 6 months after the last dose of study treatment.
10. Adequate laboratory parameters at baseline (obtained <14 days prior to randomization)
11. Patients must be able to understand and comply with the conditions of the protocol and must have read and understood the consent form and provided written informed consent.

Exclusion Criteria:

1. Pregnant or lactating females.
2. Original primary tumor or subsequent relapse known to be positive for ER, PgR, or HER2 receptors, as defined above.
3. Confirmed BRCA1 or BRCA2 mutation carrier.
4. Prior systemic therapy for metastatic or locally recurrent breast cancer.
5. Bone as the only site of disease.
6. Presence of untreated symptomatic central nervous system (CNS) metastases as determined by MRI or CT scan performed during screening.
7. Prior radiotherapy to the only area of measurable disease.
8. Prophylactic use of supportive bone-modifying therapy for skeletal-related events
9. History of recent clinical pancreatitis, according to revised Atlanta criteria, within 3 months of randomization.
10. Neurosensory neuropathy >Grade 2 at baseline.
11. Known history of infection with human immunodeficiency virus (HIV) and/or active infection with hepatitis B or hepatitis C.
12. Known hypersensitivity to gemcitabine, platinum compounds, mannitol, or asparaginase.
13. Treatment with warfarin. Warfarin must be replaced with low-molecular weight heparin.
14. History of other malignancies except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for >5 years.
15. Any other severe acute or chronic condition that may increase the risk of study participation
16. Receiving therapy in a concurrent clinical study. Patients must agree not to participate in any other interventional clinical studies during their participation in this trial while on study treatment.