Phase 1a/1b Dose Escalation and Expansion Study of SBP-101 in Combination with Nab-Paclitaxel and Gemcitabine in Subjects with Previously Untreated Metastatic Pancreatic Ductal Adenocarcinoma

Inclusion Criteria:

• Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma. Patients with pancreatic acinar cell carcinoma may also be included.
• Is previously untreated for metastatic pancreatic ductal adenocarcinoma, was diagnosed within the past 3 months, and is expected to receive standard treatment with gemcitabine and nab-paclitaxel.
• Measurable disease on CT or MRI scan by RECIST v 1.1 criteria.
• ECOG Performance Status 0 or 1.
• Adult, age ≥ 18 years, male or female.
• Females of child-bearing potential must have a negative serum pregnancy test within 14 days prior to start of study treatment and must use an adequate method of contraception during the study. All sexually active males must also use an adequate method of contraception during the study. Female subjects will be considered to be of childbearing potential unless they are postmenopausal (at least 12 months of consecutive amenorrhea, without other known or suspected cause) and over 55 years old or have been sterilized surgically (i.e., bilateral tubal ligation, hysterectomy or bilateral oophorectomy, all with surgery at least one month before dosing).

• Adequate bone marrow, hepatic, renal and coagulation function as defined by the following:

  1. Absolute neutrophil count ≥1.5 x 109/L
  2. Hemoglobin ≥9.0 g/dL (90 g/L)
  3. Platelets ≥100 x 109/L
  4. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x upper limit of normal (ULN) (if no hepatic metastases). If hepatic tumor involvement, AST and ALT ≤5 x ULN.
  5. Bilirubin ≤1.5 x ULN
  6. Prothrombin time (PT) / international normalized ratio (INR) ≤1.5 x ULN if not on anti-coagulants
  7. Calculated creatinine clearance >50 mL/min using the Cockcroft and Gault equation
• QTc interval ≤ 470 msec at Baseline.
• Life expectancy ≥ 3 months.
• Willing and able to provide written informed consent: voluntary agreement to participate in the study following disclosure of risks and procedures required, including possibility of onset of exocrine pancreatic insufficiency with subsequent requirement for life-long pancreatic enzyme replacement.

Exclusion Criteria:

• Evidence of severe or uncontrolled systemic disease or any concurrent condition that, in the opinion of the Investigator or Medical Monitor, makes it undesirable for the subject to participate in the study or that would jeopardize compliance with the protocol. Subjects with pre-existing well-controlled diabetes are not excluded.
• Medical or psychiatric conditions that compromise the subject's ability to give informed consent or to complete the protocol or a history of non-compliance
• Presence of islet-cell or pancreatic neuroendocrine tumor or mixed adenocarcinoma-neuroendocrine carcinoma
• Have symptomatic central nervous system (CNS) malignancy or metastasis. Screening of asymptomatic subjects without history of CNS metastases is not required.
• Serum albumin <30 g/L (3.0 g/dL)
• Glycosylated hemoglobin (Hgb A1C) ≥ 8.0%
• Evidence of deep vein thrombosis or pulmonary embolism or other thromboembolic event during screening
• Presence of known active bacterial, fungal, or viral infection requiring systemic therapy
• Concomitant use of drugs or supplements known to influence the expression and function of CYP3A4 and/or CYP2C8
• Known active infection with human immunodeficiency virus (HIV), hepatitis B or C
• Presence of interstitial lung disease, pulmonary fibrosis, or pulmonary hypersensitivity reaction
• Myocardial infarction within the last 12 months, severe/unstable angina, symptomatic congestive heart failure New York Heart Association (NYHA) class III or IV
• Maldigestion/malabsorption syndrome pre-dating the diagnosis of pancreatic cancer.
• Pregnant or lactating
• Major surgery within 4 weeks of the start of study treatment, without complete recovery
• Known hypersensitivity to any component of study treatments
• Participation in any other clinical investigation within 4 weeks of receiving the first dose of study drug