Neoadjuvant CCRT With Gemcitabine/Durvalumab (MEDI4736) Followed by Adjuvant Gemcitabine/Durvalumab(MEDI4736) in Resectable or Borderline Resectable Pancreatic Cancer

Inclusion Criteria:

1. Written informed consent and any locally-required authorization (eg, HIPAA in the USA,EU Data Privacy Directive in the EU) obtained from the subject prior to performing anyprotocol-related procedures, including screening evaluations
2. Age>=19 years at time of study entry
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
4. Life expectancy of >= 3months
5. Histologically proven pancreatic ductal adenocarcinoma
6. Resectable or borderline resectable based on AJCC Cancer staging system (8th ed)
7. Chemotherapy -naïve for their pancreatic cancer
8. Body weight >30kg (for durvalumab monotherapy or durvalumab + novel)
9. Adequate normal organ and marrow function as defined below: (NOTE TO AUTHOR: These areminimum criteria for studies in subjects with solid tumors and may need to be alteredbased on individual study requirements; please adjust as necessary) -Haemoglobin ≥ 9.0g/dL

• Absolute neutrophil count (ANC) 1.5 (or 1.0) x (> 1500 per mm3)
• Platelet count ≥ 100 (or 75) x 109/L (>75,000 per mm3)
• Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). This will notapply to subjects with confirmed Gilbert's syndrome (persistent or recurrenthyperbilirubinemia that is predominantly unconjugated in the absence of hemolysisor hepatic pathology), who will be allowed only in consultation with theirphysician.
• AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless livermetastases are present, in which case it must be ≤ 5x ULN
• Serum creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault

1976. or by 24-hour urine collection for determination of creatinine clearance:

10. Evidence of post-menopausal status or negative urinary or serum pregnancy test forfemale pre-menopausal subjects. Women will be considered post-menopausal if they havebeen amenorrheic for 12 months without an alternative medical cause. The followingage-specific requirements apply:
11. Subject is willing and able to comply with the protocol for the duration of the studyincluding undergoing treatment and scheduled visits and examinations including followup.

Exclusion Criteria: 25. Participation in another clinical study with an investigational product during the last 3 weeks 26. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventionalstudy 27. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab 28.Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrinetherapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies,other investigational agent) 28 days prior to the first dose of study drug 29. Mean QTinterval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs)using Fridericia's Correction (this can be removed if testing durvalumab alone and retainthis exclusion if combining durvalumab with novel agents) 30. Current or prior use ofimmunosuppressive medication within 14days (use 28 days if combining durvalumab with anovel agent) before the first dose of durvalumab, with the exceptions of intranasal andinhaled corticosteroids or systemic corticosteroids at physiological doses, which are notto exceed 10 mg/day of prednisone, or an equivalent corticosteroid. The following areexceptions to this criterion:

• Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articularinjection)
• Systemic corticosteroids at physiologic doses not to exceed <<10 mg/day>> ofprednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)

31. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy withthe exception of alopecia, vitiligo, and the laboratory values defined in theinclusion criteria

• Subjects with Grade ≥2 neuropathy will be evaluated on a case-by-case basis afterconsultation with the Study Physician.
• Subjects with irreversible toxicity not reasonably expected to be exacerbated bytreatment with durvalumab may be included only after consultation with the StudyPhysician.

32. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancertreatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg,hormone replacement therapy) is acceptable. <<amend as required based on anycombination studies with other anti-cancer agents>> 33. <<if applicable to thestudy>>Radiotherapy treatment to more than 30% of the bone marrow or with a wide fieldof radiation within 4 weeks of the first dose of study drug 34. Major surgicalprocedure (as defined by the Investigator) within 28 days prior to the first dose ofIP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
33. History of allogenic organ transplantation. 36. Active or prior documentedautoimmune or inflammatory disorders (including inflammatory bowel disease [eg,colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis],systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis,hypophysitis, uveitis, etc]). The following are exceptions to this criterion:

• Subjects with vitiligo or alopecia
• Subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on hormonereplacement
• Any chronic skin condition that does not require systemic therapy
• Subjects without active disease in the last 5 years may be included but only afterconsultation with the study physician
• Subjects with celiac disease controlled by diet alone 37. Uncontrolled intercurrentillness, including but not limited to, ongoing or active infection, symptomaticcongestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiacarrhythmia, interstitial lung disease, serious chronic gastrointestinal conditionsassociated with diarrhea, or psychiatric illness/social situations that would limitcompliance with study requirement, substantially increase risk of incurring AEs orcompromise the ability of the patient to give written informed consent 38. History ofanother primary malignancy except for
• Malignancy treated with curative intent and with no known active disease ≥5 yearsbefore the first dose of IP and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence ofdisease
• Adequately treated carcinoma in situ without evidence of disease 39. History ofleptomeningeal carcinomatosis 40. Brain metastases or spinal cord compression. 41.Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 mscalculated from 3 ECGs (within 15 minutes at 5 minutes apart) <<for durvalumabmonotherapy and durvalumab + tremelimumab combination studies this criterion can beremoved. For durvalumab ± tremelimumab in combination with an agent withpro-arrhythmic potential or where effect of the combination on QT is not known if thiscriterion should be retained. Patient safety and the cardiac SKG should be consultedas needed>>.

42. History of active primary immunodeficiency 43. Active infection includingtuberculosis (clinical evaluation that includes clinical history, physical examinationand radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or humanimmunodeficiency virus (positive HIV 1/2 antibodies). Subjects with a past or resolvedHBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] andabsence of HBsAg) are eligible. Subjects positive for hepatitis C (HCV) antibody areeligible only if polymerase chain reaction is negative for HCV RNA.
43. Current or prior use of immunosuppressive medication within 14 days before thefirst dose of durvalumab or tremelimumab. The following are exceptions to thiscriterion:

• Intranasal, inhaled, topical steroids, or local steroid injections (eg, intraarticular injection)
• Systemic corticosteroids at physiologic doses not to exceed <<10 mg/day>> ofprednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)

45. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.Note: Subjects, if enrolled, should not receive live vaccine whilst receiving IP andup to 30 days after the last dose of IP.
46. Female subjects who are pregnant or breastfeeding or male or female subjects ofreproductive potential who are not willing to employ effective birth control fromscreening to 90 days after the last dose of durvalumab monotherapy.
47. Known allergy or hypersensitivity to any of the study drugs or any of the studydrug excipients.
48. Prior randomisation or treatment in a previous durvalumab and/or tremelimumabclinical study regardless of treatment arm assignment.
49. Past medical history of ILD, drug-induced ILD, radiation pneumonitis whichrequired steroid treatment, or any evidence of clinically active interstitial lungdisease.
50. Judgment by the investigator that the patient is unsuitable to participate in thestudy and the patient is unlikely to comply with study procedures, restrictions andrequirements.