Study of Eryaspase in Combination With Chemotherapy Versus Chemotherapy Alone as 2nd-Line Treatment in PAC

Inclusion Criteria

A patient will be eligible for the study if all the following criteria are met:

• Must be 18 years of age or older.
• Must have histologically confirmed pancreatic adenocarcinoma.
• Must have Stage III or IV disease.
• Must have received one line of systemic chemotherapy in the advanced setting with or without targeted agents, immunotherapy, or radiotherapy for treatment of advanced pancreatic adenocarcinoma.
• Must have radiological evidence of disease progression following most recent prior treatment, defined as appearance of any new lesion or increase of >20% of one or more existing lesions.
• Must have measurable lesion(s) per RECIST version 1.1 by CT scan with contrast (or MRI, if the patient is allergic to CT contrast media).

NOTE: Bone disease consisting of blastic lesion only is not measurable.

• Archival or fresh tumor tissue must be available for evaluating relevant biomarkers. Formalin-fixed paraffin-embedded [FFPE] block preferred, or a minimum of 10 unstained FFPE slides of one archived block is required.

NOTE: Cytology samples from fine needle aspirates or brushing biopsies are not sufficient.

If archival tissue is unavailable and an elective biopsy can't be scheduled due to COVID, this will be waived.

• Must have adequate performance status:
• ECOG Performance Status (PS) score of 0, or
• ECOG PS score one and score ≥80 on Karnofsky Performance Status (KPS) scale. NOTE: Must have body mass index (BMI) ≥18.5 kg/m2 (obtained 12 weeks according to the investigator's clinical judgment.
• Females of childbearing potential must have a negative pregnancy test at screening and additional negative pregnancy test prior to first dose. Males and 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.
• Must have adequate laboratory parameters at baseline (obtained 60 mL/min/1.73 m2 for patients with serum creatinine levels above or below the institutional normal range.
• Acceptable coagulation parameters: plasma antithrombin III >70% and fibrinogen ≥1.5 g/L
• Serum albumin ≥3.0 g/dL.
• Patients requiring biliary stent placement must have the biliary stent placed >7 days prior to screening and must have normalization of bilirubin level after stenting.
• Must not be receiving therapy in a concurrent clinical study and must agree not to participate in any other interventional clinical studies during their participation in this trial while on study treatment. Patients taking part in surveys or observational studies are eligible to participate in this study.
• 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

A patient is not eligible to participate in the study if any of the following criteria are met:

• Resectable or borderline resectable pancreatic adenocarcinoma at the time of signing the informed consent.
• Histology other than pancreatic adenocarcinoma (for example, but not inclusive: neuroendocrine, adenosquamous, etc.).
• More than one line of prior treatment in advanced or metastatic setting.
• Patient has experienced medically significant acute decline in clinical status including
• Decline in ECOG PS to >1 (or KPS Grade 2 at baseline.
• Pregnancy or breastfeeding.
• History of infection with human immunodeficiency virus (HIV) and/or active infection with hepatitis B or hepatitis C.

NOTE: Patients with unknown status of hepatitis B or C must be tested and declared negative before randomization.

• Hypersensitivity to any of the components of the chemotherapy or ASNase.
• Patients who have received live or live attenuated vaccines within 3 weeks of randomization.
• History of other malignancies NOTE: Adequately treated non-melanoma skin cancer or curatively treated in-situ cancer of the cervix may be el