Pilot Phase 2 Study to Investigate the Preliminary Efficacy and Safety of INNO-206 in Advanced Pancreatic Cancer

Patients with metastatic, locally advanced, or unresectable pancreatic ductal carcinomas (PDA) who have failed prior chemotherapy with gemcitabine regimens have an extremely poor prognosis with progression-free survival of around 13 weeks and median overall survival of approximately 20 weeks after second line chemotherapy. Recent studies suggest that albumin may be preferentially concentrated in pancreatic cancers that appear to be starved for this protein. Thus, any molecule attached to albumin would also collect inside the tumor. Based on its postulated mechanism of action, INNO-206 may improve the activity of doxorubicin without increasing its toxicity, as has been demonstrated in animal studies, and induce enhanced anti-tumor efficacy.

This is a phase 2 open-label, pilot study evaluating the preliminary efficacy and safety of INNO-206 administered at 350 mg/m2 (260 mg/m2 doxorubicin equivalent) intravenously (IV) on Day 1 every 21 days for up to 8 consecutive cycles.

Tumor response (complete and partial response and stable disease) will be monitored at Screening, then prior to cycles 3, 5 and 7, 3 weeks after cycle 8, then every 2 months to month 8 and every 3 months to tumor progression using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, and treatment will continue every 21 days until tumor progression is observed, 8 cycles of treatment are completed or unacceptable toxicity occurs. Progression-free survival \[PFS\], stable disease at 4 months and overall survival \[OS\] will be monitored as other primary objectives. PET/CT will be performed at Baseline and Week 9 to determine change in tumor metabolic activity, and CA 19-9 will be determined serially to assess potential tumor reduction. Subjects will visit the study site every 21 days for their IV infusions, at which time safety monitoring, including AEs, a directed physical examination, laboratory evaluations (serum chemistry, complete blood count \[CBC\], and urinalysis), vital signs, weight measurements, ECOG performance status and ECGs will be performed. Cardiac function will also be followed periodically using ECHOs.

Eligibility Criteria:
Inclusion Criteria:

* Age ≥ 18 years of age; male or female.
* Histologically or cytologically confirmed, locally advanced, unresectable, and/or metastatic pancreatic ductal adenocarcinoma.
* Cancer progression after treatment with one gemcitabine and one fluoropyrimidine-containing chemotherapy regimen.
* Capable of providing informed consent and complying with trial procedures.
* ECOG performance status 0-1.
* Life expectancy ≥ 8 weeks.
* Measurable tumor lesions according to RECIST 1.1 criteria.
* Women must not be able to become pregnant (eg post-menopausal for at least 1 year, surgically sterile, or practicing adequate birth control methods) for the duration of the study. (Adequate contraception includes: oral contraception, implanted contraception, intrauterine device implanted for at least 3 months, or barrier method in conjunction with spermicide.)
* Women of child bearing potential must have a negative serum or urine pregnancy test at the Screening Visit and be non-lactating.
* Geographic accessibility to the site.

Exclusion Criteria:

* Prior exposure to \> 3 cycles or 225 mg/m2 of doxorubicin or Doxil®.
* Palliative surgery and/or radiation treatment less than 4 weeks prior to Randomization.
* Exposure to any investigational agent within 30 days of Randomization.
* Evidence of central nervous system (CNS) metastasis (negative imaging study, if clinically indicated, within 4 weeks of Screening Visit).
* History of other malignancies (except cured basal cell carcinoma, superficial bladder cancer or carcinoma in situ of the cervix) unless documented free of cancer for ≥ 5 years.
* Laboratory values: Screening serum creatinine \> 1.5x upper limit of normal (ULN), alanine aminotransferase (ALT) \> 3×ULN or \> 5×ULN if liver metastases are present, total bilirubin \> 3×ULN, absolute neutrophil count \< 1,500/mm3, platelet concentration \< 100,000/mm3, absolute lymphocyte count \< 1000/mm3, hematocrit level \< 27% for females or \< 30% for males, or coagulation tests (prothrombin time \[PT\], partial thromboplastin time \[PTT\], International Normalized Ratio \[INR\]) \> 1.5×ULN, serum albumin ≤ 2.8 g/dL.
* Clinically evident congestive heart failure \> class II of the New York Heart Association (NYHA) guidelines.
* Current, serious, clinically significant cardiac arrhythmias, defined as the existence of an absolute arrhythmia or ventricular arrhythmias classified as Lown III, IV or V.
* History or signs of active coronary artery disease with or without angina pectoris.
* Serious myocardial dysfunction ultrasound-determined, with absolute left ventricular ejection fraction (LVEF) \< 45% of predicted.
* History of HIV infection.
* Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals.
* Major surgery within 4 weeks prior to Randomization.
* Substance abuse or any condition that might interfere with the subject's participation in the study or in the evaluation of the study results.
* Any condition that is unstable and could jeopardize the subject's participation in the study.