L-DOS47 Plus Doxorubicin in Advanced Pancreatic Cancer

The Phase Ib part of the study will apply a standard 3 + 3 algorithm for dose escalation to determine the appropriate L-DOS47 maximum tolerated dose to use in combination with doxorubicin for the Phase II part of the study. Patients will be recruited into 3 cohorts where each cohort will receive increasing weekly dose levels of L-DOS47 in combination with a fixed dose of 20 mg/m2 of doxorubicin weekly. The decision for escalation to the next dose level will be made after all patients in a cohort have completed 4 weeks of combination treatment and the safety data have been reviewed by the Safety Review Committee. If a patient in any cohort experiences a dose limiting toxicity, an additional 3 patients will be enrolled, for a maximum of up to 18 patients in this initial dose escalation part of the study.

The Phase II part of the study will focus on evaluating preliminary anti-tumor activity, as well as continuing to evaluate safety and tolerability of L-DOS47 in combination with doxorubicin. A further 11 additional patients will be enrolled in this phase of the study, which is designed to ensure patient safety and to detect whether there is a level of anti-tumor activity that would be worth pursuing in a larger clinical trial. Patients will be initiated on the L-DOS47 dose determined in Phase I, in combination with 20 mg/m2 doxorubicin, with tumor marker carbohydrate antigen 19-9 (CA19-9) measurements at each treatment cycle, and radiological assessments every two treatment cycles.

Tumor response will be assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria.

Safety will be assessed by reported adverse events (AEs), serious adverse events (SAEs), physical exams, vital signs, Karnofsky Performance Status, electrocardiogram (ECG), echocardiogram (ECHO)/multigated acquisition scan (MUGA), clinical laboratory evaluations (hematology, chemistry, coagulation and urinalysis), and anti-L-DOS47 antibody levels.