Pembrolizumab Plus Chemotherapy in 1st Line Treatment of Pancreatic Cancer

Biomarker-oriented Study of Pembrolizumab in Combination With Chemotherapy in Chemotherapy -naïve Advanced Pancreatic Cancer

This is an open-label, phase 2 study of Pembrolizumab in combination with chemotherapy in chemotherapy-naïve advanced pancreatic cancer

• In unresectable advanced pancreatic cancer, palliative chemotherapy (mainly Gemcitabine/nab-Paclitaxel or FOLFIRINOX) is the mainstay of treatment. Regardless of the choice of first-line therapy, more than half of the patients with advanced/metastatic disease will progress within six months and will not survive more than one year.
• Immune cells (IC) are a significant part of the pancreatic tumor-associated stroma and play a fundamental part in maintaining a non-immunogenic and immuno-suppressive environment.
• IO (Immuno-Oncology drug) monotherapy is not effective in advanced pancreatic cancer; therefore, we need more active combination regimens including IO/IO or IO/chemotherapy, etc. Furthermore, we need biomarker study to uncover which population is an optimal target for this IO-based treatment strategy.
• Based on these rationale, we plan to conduct an open-label, phase 2 study to explore biomarkers and evaluate the safety and efficacy of the pembrolizumab/chemotherapy combination in an advanced pancreatic cancer primary environment.

Inclusion Criteria:

1. Male/female participants who are at least 18 years of age on the day of signing informed consent

2. Histologically confirmed diagnosis of unresectable, recurrent, or metastatic pancreatic cancer

3. Not pregnant, not breasfeeding, and agree to use proper contraception,

4. Chemotherapy-naïve for advanced pancreatic cancer (previous adjuvant chemotherapy is allowed)

5. Have measurable disease based on RECIST 1.1.

6. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

7. Have adequate organ function

   • Haemoglobin ≥ 9.0 g/dL
   • Absolute neutrophil count (ANC) 1.5 (or 1.0) x (> 1500 per mm3)
   • Platelet count ≥ 100 x 109/L (>75,000 per mm3)
   • Serum creatinine CL>30 mL/min by the Cockcroft-Gault formula or serum creatinine ≤1.5 × ULN
   • Serum bilirubin ≤ 1.5 x ULN
   • AST (SGOT)/ALT (SGPT) ≤ 2.5 x ULN unless liver metastases are present, in which case it must be ≤ 5x ULN
   • International normalized ratio (INR) or Prothrombin time (PT), activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy

Exclusion Criteria:

1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation
2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
3. Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks
4. Has received prior radiotherapy within 2 weeks of start of study treatment.
5. Has received a live vaccine within 30 days prior to the first dose of study drug.
6. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device
7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
8. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
9. Has known active CNS metastases and/or carcinomatous meningitis.
10. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
11. Has active autoimmune disease that has required systemic treatment in the past 2 years
12. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
13. Has an active infection requiring systemic therapy.
14. Has a known history of Human Immunodeficiency Virus (HIV).
15. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
16. Has a known history of active TB (Bacillus Tuberculosis).
17. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
18. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
19. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.