Study of Nab-Paclitaxel and Gemcitabine With or Without SBP-101 in Pancreatic Cancer

Inclusion Criteria:

• Histologically or cytologically confirmed metastatic pancreatic ductaladenocarcinoma.

• Is previously untreated for metastatic pancreatic ductal adenocarcinoma; metastaticdisease must have been diagnosed within the past 3 months; and subject is expectedto receive standard treatment with gemcitabine and nab-paclitaxel. Subjects who havehad planned or prior surgery, such as a Whipple procedure, with or withoutneo-adjuvant/or adjuvant chemotherapy may be included.

• Life expectancy ≥ 3 months.

• Measurable disease on computed tomography (CT) or magnetic resonance imaging (MRI)scan by RECIST v1.1 criteria.

• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.

• 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 ofcontraception from 2 weeks before the first administration of SBP-101 until 6 monthsafter the last administration of study drug (i.e., last dose of any of the threedrugs in the regimen). Female subjects are considered to be of childbearingpotential unless they are postmenopausal (at least 12 months of consecutiveamenorrhea, without other known or suspected cause) and over 55 years old or havebeen sterilized surgically (i.e., bilateral tubal ligation, hysterectomy, orbilateral oophorectomy, all with surgery at least one month before dosing).

• Adequate bone marrow, hepatic and renal function as outlined in protocol.

• QTc interval ≤ 470 ms (for women) and ≤ 450 ms (for men) on the ECG at baselinecalculated by either the Fridericia or Framingham formula.

• Willing and able to provide written informed consent: voluntary agreement toparticipate in the study following disclosure of risks and procedures required.

Exclusion Criteria:

• When results of germline or somatic testing done prior to screening are known,subjects known to have mutations of the BRCA 1/2 (Breast Cancer gene) are excluded.

• Concomitant metformin administration. Diabetic subjects on treatment with metformin,or any other derivative thereof, must discontinue it at least 5 days prior to C1D1and not take metformin while on study (other diabetic medications are allowed).

• Any history of retinopathy or at risk for retinal detachment (personal or familyhistory of retinal detachment, extreme myopia [-6.0 diopters or approximately 20/500], eye surgery <6 months prior to C1D1, or history of a severe eye injury.Subjects with findings of retinopathy on baseline ophthalmology exams will beexcluded.

• Evidence of severe or uncontrolled systemic disease or any concurrent conditionthat, in the opinion of the Investigator or Medical Monitor, makes it undesirablefor the subject to participate in the study or that would jeopardize compliance withthe protocol. Subjects with pre-existing well-controlled diabetes are not excluded.

• Medical or psychiatric conditions that compromise the subject's ability to giveinformed consent or to complete the protocol or a history of non-compliance.

• Presence of islet-cell or pancreatic neuroendocrine tumor or mixedadenocarcinoma-neuroendocrine carcinoma.

• Symptomatic central nervous system (CNS) malignancy or metastasis. Screening ofasymptomatic subjects without history of CNS metastases is not required.

• Serum albumin < 30 g/L (3.0 g/dL).

• Deep vein thrombosis (DVT) or portal vein occlusion, pulmonary embolism (PE), orother thromboembolic event that occurs during screening.

• Presence of known active bacterial, fungal, or viral infection requiring systemictherapy.

• Known active infection with human immunodeficiency virus (HIV), hepatitis B or C.

• Presence of interstitial lung disease, pulmonary fibrosis, or pulmonaryhypersensitivity reaction.

• Myocardial infarction within the last 12 months, severe/unstable angina, symptomaticcongestive heart failure New York Heart Association (NYHA) class III or IV.

• Pregnant or lactating.

• Major surgery within 4 weeks prior to the start of study drug treatment, withoutcomplete recovery.

• Known hypersensitivity to any component of study treatments.

• Participation in any other clinical investigation within 4 weeks of receiving thefirst dose of study drug.

• Any history of hydroxychloroquine use (Plaquenil® and other brand names).