• Age ≥ 18 years (in certain territories, the minimum age requirement may be higher, e.g. age ≥ 20 years in Taiwan)

• Written informed consent

• Patient must meet one of the following criteria based on:

• Arm A (RP72 monotherapy): Histologically or cytologically confirmed locally advanced unresectable or metastatic pancreatic cancer that has progressed on (or intolerant of) one or more standard treatment regimen(s) or for which no effective therapy is available. Note: Prior exposure to gemcitabine as a single agent or in combination with other agents (as part of multi-agent chemotherapy regimen) is acceptable.

• Or

• Arm B (RP72 in combination with Gemcitabine): Histologically or cytologically confirmed locally advanced unresectable or metastatic pancreatic cancer that has progressed on (or intolerant of) one or more standard treatment regimen(s) and is expected (or currently receiving) standard treatment with gemcitabine.Note: Patients who have already started on gemcitabine need to have no evidence of disease progression at the time of screening in order to be eligible for the study.

• Note: The definition of unresectability will follow the criteria of NCCN guidelines (Carroll et al. version 2.2016, PANC-B)

• Fasting blood glucose \<160 mg/dl, prior to study enrollment. (For higher values, blood glucose may be controlled by dietary intervention, oral hypoglycemics and/ or insulin prior to enrollment)

• Estimated life expectancy of ≥12 weeks

• Adequate hematologic and end-organ function

• Measurable / assessable disease according to RECIST v.1.1

• ECOG performance status 0 or 1

• Subjects who are eligible and able to participate in the study and accept to enter the study by signing written informed consent forms

⁃ Patients are recovered from toxicities from prior systemic therapies and have adequate hematopoietic, liver and renal function at screening and before using study medication

∙ Haemoglobin ≥ 8 g/dL

‣ Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3

‣ Absolute lymphocyte count ≥ 1000/mm3,

‣ Platelets ≥ 80,000 /mm3

‣ Total white blood cell (WBC) ≥ 3,000 cells /mm3

‣ Coagulation tests (prothrombin time \[PT\], activated partial thromboplastin time \[aPTT\], International Normalized Ratio \[INR\]) \< 1.5×ULN,

‣ Total bilirubin ≤ 1.5×ULN,

‣ Aspartate Aminotransferase (AST)/Serum Glutamic Oxaloacetic Transaminase(SGOT) and/or Alanine Aminotransferase (ALT)/Serum Glutamic Pyruvic Transaminase (SGPT) ≤ 3 x ULN (or ≤ 5×ULN if liver metastases are present

‣ Albumin \> 2.5 g/dL

‣ Creatinine Clearance (CrCl) \> 50 mL/min\[Cockcroft-Gault equation\]

⁃ All male subjects and female subjects with child-bearing potential (between puberty and 2 years after menopause) should use appropriate contraception method(s) for at least 4 weeks after RP72 treatment shown below.

∙ Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception).

‣ Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment.

‣ Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject

‣ Combination of any two of the following (a+b or a+c, or b+c):

⁃ Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate \<1%), for example hormone vaginal ring or transdermal hormone contraception.

• Placement of an intrauterine device (IUD) or intrauterine system (IUS).

• Barrier methods of contraception: Condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.