iExosomes in Combination with Ipilimumab for the Treatment of Patients with Metastatic Pancreas Cancer with KrasG12D Mutation

Inclusion Criteria

• Patients with histologically confirmed metastatic pancreatic ductal adenocarcinoma harboring KrasG12D mutation
• Patients must have documented progression disease on one or more lines of systemic therapy. If stable disease, patient must have completed at least 4 months of chemotherapy with cytotoxic therapy
• KrasG12D mutation status will be informed from any previous routine molecular profiling (using commercial assays such as Foundation One, Caris, Oncomine or other) of tissue or blood
• ECOG (Eastern Cooperative Oncology Group) performance status of 0-1
• Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
• Platelets >= 100,000/ul
• Hemoglobin > 9.0 g/dL
• Total bilirubin =< 1.5 mg/dL * In patients with known Gilbert’s syndrome, direct bilirubin =< 1.5 x upper limit of normal (ULN) will be used as organ function criteria, instead of total bilirubin
• AST (aspartate aminotransferase) and ALT (alanine transaminase) < 2.5 x ULN (upper limit of normal) * If liver metastases are present, then =< 5 x ULN is allowed
• Creatinine < 1.5 x upper limits of normal (ULN) or creatinine clearance >= 50 mL/min by Cockcroft & Gault formula
• The effects of iExosomes and ipilimumab on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for at least 12 weeks after the last dose of study drug. This includes all female patients, between the age of 18 and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following: * Postmenopausal (no menses in greater than or equal to 12 consecutive months) * History of hysterectomy or bilateral salpingo-oophorectomy * Ovarian failure (follicle stimulating hormone and estradiol in menopausal range, who have received whole pelvic radiation therapy) * History of bilateral tubal ligation or another surgical sterilization procedure
• Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), intrauterine device (IUD), tubal ligation or hysterectomy, subject/partner post vasectomy, implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and a drug washout period of four weeks following last trial related therapy of any sort is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 12 weeks after completion of study treatment
• Patients must sign an informed consent and authorization indicating that they are aware of the investigational nature of this study and the known risks involved
• Patient is >= 18 years of age on the day of consenting to the study

Exclusion Criteria

• Concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study such as unstable angina, myocardial infarction within 6 months, unstable symptomatic arrhythmia, uncontrolled diabetes, serious active or uncontrolled infection
• Pregnant women are excluded from this study because iExosomes and ipilimumab have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with iExosomes and/or ipilimumab, breastfeeding should be discontinued if the mother is treated with either of these agents. These potential risks may also apply to other agents used in this study
• Known central nervous system (CNS) disease, except for treated brain metastasis. Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (magnetic resonance imaging-MRI or computerized tomography-CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; gamma knife, linear accelerator [LINAC], or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to day 1 will be excluded
• A diagnosis of immunodeficiency or is receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• Prior solid organ or hematologic transplant
• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
• Known and untreated hepatitis B or hepatitis C