| Eligibility |
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 any
protocol-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 are
minimum criteria for studies in subjects with solid tumors and may need to be altered
based on individual study requirements; please adjust as necessary) -Haemoglobin = 9.0
g/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 not
apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent
hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis
or hepatic pathology), who will be allowed only in consultation with their
physician.
- AST (SGOT)/ALT (SGPT) = 2.5 x institutional upper limit of normal unless liver
metastases 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 for
female pre-menopausal subjects. Women will be considered post-menopausal if they have
been amenorrheic for 12 months without an alternative medical cause. The following
age-specific requirements apply:
11. Subject is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations including follow
up.
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 interventional
study 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, endocrine
therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies,
other investigational agent) 28 days prior to the first dose of study drug 29. Mean QT
interval 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 retain
this exclusion if combining durvalumab with novel agents) 30. Current or prior use of
immunosuppressive medication within 14days (use 28 days if combining durvalumab with a
novel agent) before the first dose of durvalumab, with the exceptions of intranasal and
inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not
to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. The following are
exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular
injection)
- Systemic corticosteroids at physiologic doses not to exceed <<10 mg/day>> of
prednisone 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 with
the exception of alopecia, vitiligo, and the laboratory values defined in the
inclusion criteria
- Subjects with Grade =2 neuropathy will be evaluated on a case-by-case basis after
consultation with the Study Physician.
- Subjects with irreversible toxicity not reasonably expected to be exacerbated by
treatment with durvalumab may be included only after consultation with the Study
Physician.
32. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer
treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg,
hormone replacement therapy) is acceptable. <<amend as required based on any
combination studies with other anti-cancer agents>> 33. <<if applicable to the
study>>Radiotherapy treatment to more than 30% of the bone marrow or with a wide field
of radiation within 4 weeks of the first dose of study drug 34. Major surgical
procedure (as defined by the Investigator) within 28 days prior to the first dose of
IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
35. History of allogenic organ transplantation. 36. Active or prior documented
autoimmune 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 hormone
replacement
- Any chronic skin condition that does not require systemic therapy
- Subjects without active disease in the last 5 years may be included but only after
consultation with the study physician
- Subjects with celiac disease controlled by diet alone 37. Uncontrolled intercurrent
illness, including but not limited to, ongoing or active infection, symptomatic
congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac
arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions
associated with diarrhea, or psychiatric illness/social situations that would limit
compliance with study requirement, substantially increase risk of incurring AEs or
compromise the ability of the patient to give written informed consent 38. History of
another primary malignancy except for
- Malignancy treated with curative intent and with no known active disease =5 years
before the first dose of IP and of low potential risk for recurrence
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of
disease
- Adequately treated carcinoma in situ without evidence of disease 39. History of
leptomeningeal carcinomatosis 40. Brain metastases or spinal cord compression. 41.
Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) =470 ms
calculated from 3 ECGs (within 15 minutes at 5 minutes apart) <<for durvalumab
monotherapy and durvalumab + tremelimumab combination studies this criterion can be
removed. For durvalumab ± tremelimumab in combination with an agent with
pro-arrhythmic potential or where effect of the combination on QT is not known if this
criterion should be retained. Patient safety and the cardiac SKG should be consulted
as needed>>.
42. History of active primary immunodeficiency 43. Active infection including
tuberculosis (clinical evaluation that includes clinical history, physical examination
and radiographic findings, and TB testing in line with local practice), hepatitis B
(known positive HBV surface antigen (HBsAg) result), hepatitis C, or human
immunodeficiency virus (positive HIV 1/2 antibodies). Subjects with a past or resolved
HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and
absence of HBsAg) are eligible. Subjects positive for hepatitis C (HCV) antibody are
eligible only if polymerase chain reaction is negative for HCV RNA.
44. Current or prior use of immunosuppressive medication within 14 days before the
first dose of durvalumab or tremelimumab. The following are exceptions to this
criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra
articular injection)
- Systemic corticosteroids at physiologic doses not to exceed <<10 mg/day>> of
prednisone 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 and
up to 30 days after the last dose of IP.
46. Female subjects who are pregnant or breastfeeding or male or female subjects of
reproductive potential who are not willing to employ effective birth control from
screening 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 study
drug excipients.
48. Prior randomisation or treatment in a previous durvalumab and/or tremelimumab
clinical study regardless of treatment arm assignment.
49. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which
required steroid treatment, or any evidence of clinically active interstitial lung
disease.
50. Judgment by the investigator that the patient is unsuitable to participate in the
study and the patient is unlikely to comply with study procedures, restrictions and
requirements.
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