This is a dual arm, open label phase I/II study to evaluate the safety and clinical activity
of the combination of durvalumab with CV301 in combination with maintenance chemotherapy for
patients with metastatic colorectal or pancreatic cancer whose disease is stable on, or
responding to 1st line therapy for metastatic disease. Patients with metastatic colorectal or
pancreatic adenocarcinoma who still have an adequate performance status and normal hepatic
and renal function will be eligible.
1. Histologically proven metastatic pancreatic or colorectal adenocarcinoma with
measurable disease, defined as at least 1 unidimensionally measurable lesion on a CT
scan as defined by RECIST 1.1 criteria.
2. Stable on, or responding to 1st line therapy for metastatic disease
1. At least 8 and not more than 16 weeks after initiating 1st line therapy for
2. Tumor stability/response on 1st line therapy will be determined as per RECIST 1.1
3. Prior adjuvant chemotherapy is allowed, as long as a minimum of 3 months (for
pancreatic cancer) and 6 months (for colorectal cancer) has passed between the
completion of adjuvant therapy and the start of first line therapy
4. Disease that is amenable to serial biopsies
5. ECOG performance status 0-1
6. Age >= 18 years
7. Blood pressure <160/100 mmHg
8. Adequate hepatic, bone marrow, and renal function:
1. Bone Marrow: Absolute neutrophil count (ANC) ≥ 1,500/mm3; Platelets ≥
100,000/mm3; Hemoglobin ≥ 9.0 g/dL
2. Renal function: Serum creatinine ≤ 1.5 X upper normal limit of institution's
normal range OR creatinine clearance ≥ 40 mL/min/1.73 m2 for subjects with
creatinine levels above institutional normal. Creatinine clearance should be
determined by the Cockcroft-Gault formula (below) or by 24-hour urine collection
for determination of creatinine clearance:
Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL)
Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine
3. Hepatic function: AST and ALT ≤ 2.5 X the upper normal limit of institution's
normal range. Non-fasting bilirubin ≤ 1.5 X the upper normal limit of
institution's normal range.
9. Partial Thromboplastin Time (PTT) must be ≤ 1.5 X upper normal limit of institution's
normal range and INR (International Normalized Ratio) ≤ 1.5. Subjects on anticoagulant
(such as coumadin) will be permitted to enroll as long as the INR is in the acceptable
therapeutic range as determined by the investigator. Due to the drug-drug interaction
between warfarin and capecitabine, alternate anticoagulation should be considered.
10. Life expectancy > 12 weeks.
11. Women of childbearing potential must have a negative serum or urine pregnancy test
within 28 days prior to initiation of treatment AND confirmed prior to initiation of
treatment on Day 1.
12. Alternatively, female subjects must be of non-reproductive potential (ie,
post-menopausal by history: ≥60 years old and no menses for ≥1 year without an
alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal
ligation, OR history of bilateral oophorectomy).
13. Subject is capable of understanding and complying with parameters as outlined in the
protocol and able to sign and date the informed consents, approved by the
Institutional Review Board (IRB), prior to the initiation of any screening or
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
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
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,
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.