Phase II of BAX2398/5-FU/Calcium Levofolinate in Pancreatic Cancer

Study Part 1: To assess the safety and tolerability, and to characterize the pharmacokinetics (PK) of BAX2398 in combination with 5-FU/calcium levofolinate in Japanese patients.

Study Part 2: To compare the efficacy of BAX2398 in combination with 5-FU/calcium levofolinate versus 5-FU/calcium levofolinate as assessed by Progression Free Survival (PFS) using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1).


Eligibility Criteria:
Inclusion Criteria:

1. Participant is ≥20 years of age at the time of screening.
2. Histologically or cytologically confirmed adenocarcinoma of exocrine pancreas
3. Documented metastatic disease
4. Metastatic disease with at least one measurable lesion as defined by RECIST 1.1 guidelines
5. Documented disease progression after prior gemcitabine or any gemcitabine containing therapy but excluding irinotecan, for locally advanced or metastatic setting. Prior chemotherapy must be stopped for at least 21 days before the first dose.
6. Karnofsky Performance Status (KPS) ≥70
7. Adequate bone marrow reserves
8. Adequate hepatic function
9. Adequate renal function
10. Normal ECG including Fridericia corrected QT interval (QTcF) \<440 ms within 7 days prior to first dose of study drug
11. Recovered from the effects of any prior surgery, radiotherapy or other anti-neoplastic therapy with no residual adverse events (AEs) of Grade ≥2.
12. Able to understand and sign an informed consent (or have a legal representative who is able to do so)
13. If female of childbearing potential, participant presents with a negative pregnancy, and agrees to employ adequate birth control measures during the study dosing period and for 3 months following the last dose of study drug.
14. Participant is willing and able to comply with the requirements of the protocol.

Exclusion Criteria:

1. Active and uncontrolled central nervous system (CNS) metastases; for controlled CNS metastases, patient should have been off steroids for at least 28 days prior to starting study therapy.
2. History of any second malignancy in the last 5 years; participants with prior history of in-situ cancer or basal or squamous cell skin cancers are eligible. Participants with other malignancies are eligible if they have been continuously disease free for at least 5 years.
3. Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) less than 6 months before inclusion.
4. Cannot stop medications that are potent CYP3A4 inducers within 2 weeks and inhibitors within 1 week before start of treatment.
5. Significant cardiac conduction abnormalities, including a history of long QTcF syndrome and/or pacemaker.
6. New York Heart Association (NYHA) Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure.
7. Active infection, including active hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV, or an unexplained fever \>38.5°C during screening visits or on the first scheduled day of dosing (at the discretion of the investigator, patients with tumor fever may be enrolled), which in the investigator's opinion might compromise the patient's participation in the trial or affect the study outcome.
8. Known hypersensitivity to any of the components of BAX2398, other liposomal products, fluoropyrimidines, or calcium levofolinate.
9. Any other medical or social condition deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results.
10. Participant has been exposed to an investigational product (IP) within 30 days prior to the first dose of the study drug or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study.
11. Participant is a family member or employee of the investigator.
12. Participant is pregnant or lactating at the time of enrollment. Lactating mothers can resume breast feeding 30 days following the last dose of the study treatment.