Inclusion criteria:
1. Histological or pathological confirmation of metastatic pancreas adenocarcinoma
1. Cytologic or histologic proof of pancreas adenocarcinoma needs to be verified by
the treating institution pathologist, either from the initial diagnostic biopsy
or from the required pre-treatment biopsy, prior to initiation of any
study-related therapy.
2. Pathologic confirmation of metastatic (stage IV) disease (unresectable) on
research pretreatment biopsy is required prior to initiation of therapy.
3. Patients with endocrine or acinar pancreatic carcinoma are not eligible for the
study.
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
3. Age ≥18 years
4. Adequate hematological and end-organ function (test results from within 14 days prior
to initiation of study treatment):
1. Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L without granulocyte
colony-stimulating factor support
2. White Blood Cell Count (WBC) count ≥ 2.5 x 109 /L (2500/uL)
3. Lymphocyte count ≥ 0.5 x 109/L (500/uL)
4. Platelet count ≥ 100 x 109/L (100,000/uL) without transfusion
5. Hgb ≥ 9.0 g/dL
6. Aspartate aminotransferase (AST), alanine transaminase (ALT), and alkaline
phosphatase (ALP) ≤ 2.5X upper limit of normal (ULN), unless elevated secondary
to biliary obstruction from the pancreas mass and amenable to decompression prior
to initiation of therapy
7. Serum total bilirubin ≤ 1.5X ULN, unless in patients with known Gilbert disease
(≤ 3X ULN), or unless elevated secondary to biliary obstruction from the pancreas
mass and amenable to decompression prior to administration of investigational
therapy
8. Albumin ≥ 3.5 g/dL
9. Creatinine within ULN or calculated creatinine clearance (CrCl) >50 mL/min using
the Cockcroft-Gault formula
10. International normalized ratio (INR) and activated partial thromboplastin time
(aPTT) ≤ 1.5X ULN, except for those on stable anticoagulation for at least two
weeks
5. Measurable disease according to Immune Modified (IM)-RECIST and tumor accessible for
fresh biopsy
6. Negative pregnancy test: Women of child-bearing potential must have a negative serum
pregnancy test at screening and must agree to use an effective form of contraception
from the time of the negative pregnancy test until a minimum of 3 months after the
last dose of study drug. Effective forms of contraception include abstinence, hormonal
contraceptive (injectable or implantable) in conjunction with a barrier method. Women
of non-child-bearing potential must have been postmenopausal for ≥ 1 year or
surgically sterile.
7. Birth control agreement: Fertile men must agree to use an effective method of birth
control with female partners of childbearing potential (condoms plus an additional
contraceptive method such as an injectable or implantable hormonal contraceptive)
during the study and for up to 3 months after the last dose of study drug.
8. Informed consent: Participants must be willing and able to provide written informed
consent prior to any study-related procedures and to comply with all study
requirements.
9. Ability to comply: Participants must be able to comply with the study protocol,
according to the investigator's judgement.
10. DVT testing Participants must have undergone lower extremity dopplers to rule out deep
venous thrombosis (DVT) within the screening period, and undergo therapeutic
anticoagulation if evidence of DVT is identified.
11. Anticoagulation treatment Subjects who are stable on full-dose anticoagulation
medication for at least 2 weeks are considered eligible. However, subjects who have an
increased clot burden on full-dose anticoagulation, such as central pulmonary
embolism, or peripheral pulmonary embolism, and DVT within the extremities will be
considered eligible only with the approval of the Principal Investigator.
Exclusion criteria:
1. Prior systemic therapy for PDAC: Participants may not have had systemic chemotherapy,
investigational therapy, or treatment with T-cell co-stimulating or immune check point
blockade therapies (including anti-CTLA-4, anti PD-1, and anti PD-L1 therapeutic
antibodies) prior to initiation of study treatment.
2. Prior radiation therapy for PDAC Participants may not have had radiation therapy to
within two weeks prior to initiation of study treatment. Participants may not have had
previous radiotherapy to the primary pancreas lesion or a metastatic site except for
palliation for pain. Participants who receive radiation to 25% or more of the bone
marrow will be excluded.
3. Prior surgery for PDAC Participants may not have had surgical resection of PDAC prior
to initiation of study treatment
4. Patients currently receiving any other investigational agents
5. Adverse events from prior anti-cancer therapy that have not resolved to Grade ≤ 1 or
better, with the exception of alopecia of any grade and Grade ≤ 2 peripheral
neuropathy
6. Concomitant treatment with other anti-neoplastic agents (hormone therapy acceptable)
7. Uncontrolled pleural effusion, pericardial effusion, or ascites. Subjects who required
drainage within the four weeks prior or require pleural, pericardial, or peritoneal
catheters for drainage are ineligible.
8. Uncontrolled tumor-related pain Patients requiring narcotic pain medication must be on
a stable regimen for at least two weeks prior to study entry.
9. History of leptomeningeal or brain/ Central Nervous System (CNS) metastases
10. Uncontrolled hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL, or
corrected serum calcium > upper limit of normal) or symptomatic hypercalcemia
requiring continued use of bisphosphonate therapy.
11. Recent major surgery or significant traumatic injury Participants may not have
undergone major surgery or experienced significant traumatic injury within 14 days
prior to initiating study treatment, or be recovering from procedure related adverse
events of > Grade 1.
12. Active or history of autoimmune disease or immune deficiency Includes, but is not
limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid
antibody syndrome, Wegener granulomatosis, Sjögren's syndrome, Guillain-Barré
syndrome, or multiple sclerosis, with the following exceptions:
1. Patients with a history of autoimmune-related hypothyroidism who are on stable
thyroid-replacement hormone for the past three months are eligible for the study.
2. Patients with controlled Type 1 diabetes mellitus who are on a stable insulin
regimen for the past month are eligible for the study.
3. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with
dermatologic manifestations only (e.g., patients with psoriatic arthritis are
excluded) are eligible for the study provided all of following conditions are
met:
- Rash must cover <10% of body surface area;
- Disease is well-controlled at baseline and requires only low-potency topical
corticosteroids;
- No occurrence of acute exacerbations of the underlying condition requiring
psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic
agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids
within the previous 12 months.
13. History of idiopathic pulmonary fibrosis, interstitial lung disease, organizing
pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic
pneumonitis, or evidence of active pneumonitis on screening chest computed tomography
scan (history of radiation pneumonitis or fibrosis in the radiation field is
permitted).
14. Positive for HIV at screening or any time prior to screening Patients without prior
positive HIV test result will undergo an HIV test at screening, unless not permitted
under local regulations.
15. Hepatitis B virus (HBV) infection (chronic or acute) Defined as having a positive
hepatitis B surface antigen (HBsAg) test at screening. Patients with a past or
resolved HBV infection, defined as having a negative HBsAg test and a positive total
hepatitis B core antibody test at screening, are eligible for the study.
16. Active hepatitis C virus (HCV) infection: Defined as positive HCV antibody test
followed by a positive HCV RNA test at screening.
The HCV RNA test will be performed only for patients who have a positive HCV antibody
test.
17. Known clinically significant liver disease, including alcoholic hepatitis, cirrhosis,
fatty liver disease, and inherited liver disease.
18. Active tuberculosis
19. Infection: Patients may not have had a severe infection requiring antibiotic treatment
within the two weeks prior to initiation of study treatment. This includes, but is not
limited to, hospitalization for complications of infection, bacteremia, or severe
pneumonia. However, patients who were admitted for biliary tract infection due to bile
duct obstruction at time of diagnosis must have a functioning biliary stent (as
evidenced by declining total bilirubin and ≤ 2X ULN) and resolved infection (defined
by normalization of elevated white blood cell count, absence of signs of infection)
and completion of an antibiotic course (at least a seven-day course) prior to
initiation of therapy. Patients receiving prophylactic antibiotics (e.g., to prevent a
urinary tract infection or chronic obstructive pulmonary disease exacerbation) are
eligible for the study.
20. Significant cardiovascular disease: Patient may not have significant cardiovascular
disease (such as New York Heart Association Class II or greater cardiac disease,
myocardial infarction, or cerebrovascular accident) within 12 months prior to
initiation of study treatment, seizure disorder, uncontrolled hypertension, or
unstable arrhythmia or unstable angina within 3 months prior to initiation of study
treatment.
21. Left ventricular ejection fraction below institutional lower limit of normal or below
50%, whichever is lower.
22. Baseline QTcF ≥ 450 ms (males) or ≥ 470 ms (females)
23. Grade ≥ 3 hemorrhage or bleeding event within 28 days prior to initiation of study
treatment
24. Prior autologous stem cell, allogeneic stem cell, or solid organ transplantation
25. History of other malignancy Patient may not have a history of malignancy other than
PDAC within two years prior to screening, with the exception of those with a
negligible risk of metastasis or death (e.g., 5- year overall survival of > 90%), such
as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma,
localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.
26. Recent vaccination: Patients may not have been treated with a live, attenuated vaccine
within four weeks prior to initiation of study treatment, or anticipate the need for
such a vaccine during treatment with cemiplimab or within five months after the last
dose of cemiplimab.
27. History of severe allergic anaphylactic reactions to chimeric or humanized antibodies
or fusion proteins
28. Known allergy or hypersensitivity to any of the study drug excipients
29. Recent immunosuppressive treatment: Patients may not have been treated with systemic
immunosuppressive medication (including, but not limited to, corticosteroids,
cyclophosphamide, azathioprine, methotrexate, thalidomide, calcineurin inhibitors, and
anti-tumor necrosis factor alpha agents) within two weeks prior to initiation of study
treatment, or anticipate the need for systemic immunosuppressive medication during the
course of the study, with the following exceptions:
a. Patients who received a one-time pulse dose of systemic immunosuppressant
medication are eligible for the study after approval from the Principal Investigator.
30. Pregnancy: Pregnant women are excluded from this study because there is an unknown,
but potential risk for adverse events to the fetus. Breastfeeding should be
discontinued prior to start of treatment because there is an unknown, but potential
risk for adverse events in nursing infants secondary to treatment.
31. Other contraindicated conditions Any other disease, metabolic dysfunction, physical
examination finding, or clinical laboratory finding that contraindicates the use of an
investigational drug, may affect the interpretation of the results, or may render the
patient at high risk from treatment complications in the opinion of the treating
investigator.
32. Uncontrolled psoriasis, porphyria, proximal myopathy or neuropathy
33. Severe depression Subjects hospitalized for depression within the past two years, or
who have prior suicidal attempts will be excluded.
34. Has received transfusions of blood products (including platelets or red blood cells)
within 4 weeks prior to study Day 1.
35. Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for
chronic obstructive pulmonary disease or asthma, or low-dose corticosteroids for
orthostatic hypotension or adrenal insufficiency are eligible for the study if
receiving equivalent to ≤ 10 mg of prednisone daily (10mg prednisone is equivalent to
either cortisone - 50mg; hydrocortisone - 40mg; triamcinolone - 8mg; prednisolone -
10mg; methylprednisolone - 8mg; betamethasone - 1.5mg; or dexamethasone - 1.5mg).
Patients receiving > 10 mg of prednisone or equivalent per day for greater than five
days within 28 days of starting study related therapy are not eligible. Steroids
administered prior to gemcitabine and nab-paclitaxel should be administered as per
standard institutional guidelines.
