Durvalumab Plus CV301 With Maintenance Chemotherapy in Metastatic Colorectal or Pancreatic Adenocarcinoma

Exclusion Criteria

• •1. Any prior immunotherapy or vaccine therapy
• •2. History of active or prior documented autoimmune disease within the past 2 years including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, auto-immune Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis, with the following caveats:
• •* Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible.
• •* Patients with Grave's disease, vitiligo, autoimmune alopecia, or psoriasis not requiring systemic treatment (within the past 2 years) are eligible upon consultation with the Study Chairs
• •* Patients with questionable diagnosis of autoimmune disease who have never been treated with immunosuppressive regimen and have no ongoing symptoms at the time of enrollment may be eligible after discussion with medical monitor and principle investigator
• •3. Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and TNFα antagonists) within 28 days prior to Week 1, Day 1
• •* Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled in the study after discussion with and approval by the Study Co-chairs.
• •* The use of inhaled, intranasal, ophthalmic or topical corticosteroids is allowed
• •* The use of mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension is allowed.
• •* Physiologic doses of systemic corticosteroids at doses which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
• •* High dose steroid pre-treatment for CT contrast dye allergy is allowed, provided the dose(s) of steroids is(are) given at least 1 week prior to starting the study medications
• •4. History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest CT scan
• •o History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• •5. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
• •6. Positive test for HIV infection
• •7. Active hepatitis B (defined as having a positive hepatitis B surface antigen \[HBsAg\] test at screening)
• •o Patients with past or resolved hepatitis B infection (defined as having a negative HBsAg test and a positive IgG antibody to hepatitis B core antigen \[anti-HBc\] OR negative HBV viral load by PCR) are eligible.
• •8. Active hepatitis C
• •o Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV RNA.
• •9. Active tuberculosis OR known history of previous clinical diagnosis of tuberculosis
• •10. Severe infections within 4 weeks prior to Week 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
• •o Any course of oral or IV antibiotics must have been completed at least 2 weeks prior to the first dose of study medications
• •11. Signs or symptoms of infection within 2 weeks prior to Week 1, Day 1
• •12. Received oral or IV antibiotics within 2 weeks prior to Week 1, Day 1
• •o Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible.
• •13. Prior allogeneic bone marrow transplantation or prior solid organ transplantation
• •14. Administration of a live, attenuated vaccine within 30 days before Week 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study
• •o Influenza vaccination should be given during influenza season only. Patients must not receive live, attenuated influenza vaccine (e.g., FluMistTM) within 4 weeks prior to Week 1, Day 1 or at any time during the study.
• •15. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• •16. Any anti-cancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, within 2 weeks prior to initiation of study treatment, with the following exceptions:
• •* Hormone-replacement therapy or oral contraceptives
• •* Herbal therapy \> 1 week before Week 1, Day 1 (herbal therapy intended as anti-cancer therapy must be discontinued at least 1 week before Week 1, Day 1)
• •17. CNS metastases including a history of leptomeningeal carcinomatosis
• •18. Subjects with uncontrolled seizures
• •19. The subject has had another active malignancy within the past five years except for cervical cancer in situ, in situ carcinoma of the bladder or non-melanoma carcinoma of the skin. Questions regarding the inclusion of individual subjects should be directed to the Principle Investigator.
• •20. Cardiovascular disease including unstable angina, therapy for life-threatening ventricular arrhythmia, or myocardial infarction, stroke, or congestive heart failure within the last 6 months
• •21. Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Frediricia's Correction
• •22. Life-threatening visceral disease or other severe concurrent disease
• •23. Grade ≥2 proteinuria at screening (or known prior)
• •24. Women who are pregnant or breastfeeding, or male or female patients of reproductive potential who are not employing two highly effective and acceptable forms of contraception throughout their participation in the study and for 90 days after last dose of study drug.
• •25. Patients concurrently receiving any other investigational agents.
• •26. History of allergic reactions attributed to compounds of similar chemical or biologic composition to durvalumab or any excipient or any egg products
• •27. Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.