Immunotherapy (BMS-813160 and Nivolumab) with or without a Vaccine (GVAX) after Chemotherapy and Radiation Therapy for the Treatment of Unresectable, Locally Advanced Pancreatic Cancer

Inclusion Criteria

• Patients with histologically- or cytologically-proven, surgically unresectable, locally advanced pancreatic adenocarcinoma (at diagnosis) by National Comprehensive Cancer Network (NCCN) guidelines, as determined by review of imaging and pathology at our institution
• If the patient does not have a diagnostic biopsy that is adequate for review at our institution, the patient must agree to a research core biopsy to be performed at Johns Hopkins
• If the patient’s available imaging is not adequate for review by our institution, the patient must agree to a repeat imaging to be performed at Johns Hopkins
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Life expectancy greater than 3 months
• Able to swallow pills or capsules and tolerate oral medication
• Patients must be eligible to receive fluorouracil, irinotecan, leucovorin and oxaliplatin (FOLFIRINOX)-based chemotherapy per treating (can be non-study) medical oncologist
• Patients must be willing to be treated with stereotactic body radiation therapy (SBRT) only at Johns Hopkins Hospital
• Patients must be willing to undergo a core biopsy of the pancreatic cancer during endoscopic ultrasound (EUS)-guided fiduciary placement at Johns Hopkins Hospital
• Patients must be willing to undergo a biopsy of the pancreatic cancer at Johns Hopkins Hospital if the patient is not deemed a surgical candidate during the pre-surgical evaluation
• Patients must inform any and all partner(s) of their participation in a clinical drug study and the need to comply with contraception instructions as directed by the investigator
• Female patient of childbearing potential (WOCBP) (defined below) must have a negative urine or serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]). If the urine test is positive or cannot be confirmed as negative, a negative serum pregnancy test will be required for the patient to be eligible. If a patient has a positive serum pregnancy test, then an ultrasound must be done to rule out pregnancy to enroll on trial. * A woman is considered of childbearing potential (WOCBP) following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy * Women in the following categories are not considered WOCBP: ** Pre-menarchal ** Pre-menopausal female with one of the following: *** Documented hysterectomy *** Documented bilateral salpingectomy or tubal ligation *** Documented bilateral oophorectomy ** Postmenopausal female - A postmenopausal state is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes. In addition, females under the age of 55 years must have a serum follicle stimulating hormone, (FSH) level > 40 mIU/mL to confirm menopause
• WOCBP must use one of the highly effective methods of contraception (which have a failure rate of < 1% when used consistently and correctly) listed here during study duration and through 5 months after the end of study treatment. Approved contraceptive methods include combined (estrogen- and progestogen-containing) hormonal contraception (oral, intravaginal, transdermal), progestogen-only hormonal contraception (oral, injectable), implantable progestogen-only hormonal contraception, other hormonal methods of contraception (vaginal ring, injectables, implants and intrauterine hormone-releasing system), intrauterine device and bilateral tubal occlusion. A vasectomized partner is a highly effective contraception method provided that the partner is the sole male sexual partner of the WOCBP and the absence of sperm has been confirmed. If not, an additional highly effective method of contraception should be used. Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drug. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant. It is not necessary to use any other method of contraception when complete abstinence is elected. WOCBP participants who choose complete abstinence must continue to have pregnancy tests. Acceptable alternate methods of highly effective contraception must be discussed in the event that the WOCBP participants chooses to forego complete abstinence. The following are unacceptable methods of contraception: * Male or female condom with or without spermicide. Male and female condoms cannot be used simultaneously * Diaphragm with spermicide * Cervical cap with spermicide * Vaginal sponge with spermicide * Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mechanism of action * Periodic abstinence (calendar, symptothermal, post-ovulation methods) * Withdrawal (coitus interruptus) * Spermicide only * Lactation amenorrhea method (LAM)
• Male participants with female partners of childbearing potential are eligible to participate if they agree to the following during the treatment and until the end of relevant systemic exposure * Inform any and all partner(s) of their participation in a clinical drug study and the need to comply with contraception instructions as directed by the investigator * Male participants are required to use a condom for study duration and until 7 months after the end of study treatment * Female partners of males participating in the study to consider use of effective methods of contraception until 7 months after the end of treatment in the male participant * Male participants with a pregnant or breastfeeding partner must agree to remain abstinent from penile vaginal intercourse or use a male condom during each episode of penile penetration during the treatment and until 7 months after the end of study treatment * Refrain from donating sperm for the duration of the study treatment and until 7 months after the end of study treatment * Confirmed azoospermic males are exempt from contraceptive requirements
• Ability to understand and the willingness to sign a written informed consent document
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Patients must have received 8-16 14-day cycles of FOLFIRINOX-based chemotherapy (i.e. FOLFIRINOX, fluorouracil [5-FU]/leucovorin, leucovorin calcium [calcium folinate], fluorouracil [5-fluorouracil], and irinotecan [FOLFIRI]). Patients may have received gemcitabine/nab-paclitaxel (Abraxane) due to intolerance of FOLFIRINOX, but cannot have switched chemotherapy regimens due to progression or lack of response
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Patients must have completed SBRT (recommend 6.6 Gy x 5 days) at Johns Hopkins Hospital
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to grade 1 (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version [v] 5.0) or baseline before administration of study treatment. Participants with toxicities attributed to prior anti-cancer therapy that are not expected to resolve and result in long lasting sequelae, such as neuropathy after platinum-based therapy, are permitted to enroll
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: ECOG performance status 0-1
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Able to swallow pills or capsules and tolerate oral medication
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: White blood cell count >= 2,000 cells/mm^3
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Absolute lymphocyte count >= 500 cells/mm^3
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Absolute neutrophil count >= 1,000 cells/mm^3
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Hemoglobin >= 9 g/dL * Transfusion to achieve this level is not permitted within 2 weeks of cycle 1 day 1 of immunotherapy
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Platelets >= 80,000 cells/mm^3 * Transfusion to achieve this level is not permitted within 2 weeks of cycle 1 day 1 of immunotherapy
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: AST and ALT =< 3 x ULN
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Total bilirubin =< 1.5 x ULN * Subjects with Gilbert syndrome may proceed as long as total bilirubin < 3.0 mg/dL
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Serum creatinine < 1.5 x ULN or creatinine clearance (CrCl) > 40 mL/min (measured using the Cockcroft-Gault formula)
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Patients must inform any and all partner(s) of their participation in a clinical drug study and the need to comply with contraception instructions as directed by the investigator
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Female patient of childbearing potential (WOCBP) (defined below) must have a negative urine or serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of study treatment). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required to be shown as negative for the patient to be eligible. If a patient has a positive serum pregnancy test, then an ultrasound must be done to rule out pregnancy to continue on trial * A woman is considered of childbearing potential (WOCBP) following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy * Women in the following categories are not considered WOCBP: ** Pre-menarchal ** Pre-menopausal female with one of the following: *** Documented hysterectomy *** Documented bilateral salpingectomy or tubal ligation *** Documented bilateral oophorectomy ** Postmenopausal female - A postmenopausal state is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes. In addition, females under the age of 55 years must have a serum follicle stimulating hormone, (FSH) level > 40 mIU/mL to confirm menopause
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: WOCBP must be willing to use one of the highly effective methods of contraception (which have a failure rate of < 1% when used consistently and correctly) listed here during study duration and until the end of relevant systemic exposure, starting with visit 1 through 5 months after the end of study treatment. Approved contraceptive methods include combined (estrogen- and progestogen-containing) hormonal contraception (oral, intravaginal, transdermal), progestogen-only hormonal contraception (oral, injectable), implantable progestogen-only hormonal contraception, other hormonal methods of contraception (vaginal ring, injectables, implants and intrauterine hormone-releasing system), intrauterine device and bilateral tubal occlusion. A vasectomized partner is a highly effective contraception method provided that the partner is the sole male sexual partner of the WOCBP and the absence of sperm has been confirmed. If not, an additional highly effective method of contraception should be used. Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drug. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant. It is not necessary to use any other method of contraception when complete abstinence is elected. WOCBP participants who choose complete abstinence must continue to have pregnancy tests. Acceptable alternate methods of highly effective contraception must be discussed in the event that the WOCBP participants chooses to forego complete abstinence. The following are unacceptable methods of contraception: * Male or female condom with or without spermicide. Male and female condoms cannot be used simultaneously * Diaphragm with spermicide * Cervical cap with spermicide * Vaginal sponge with spermicide * Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mechanism of action * Periodic abstinence (calendar, symptothermal, post-ovulation methods) * Withdrawal (coitus interruptus) * Spermicide only * Lactation amenorrhea method (LAM)
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Male participants with female partners of childbearing potential are eligible to participate if they agree to the following during the treatment and until the end of relevant systemic exposure * Inform any and all partner(s) of their participation in a clinical drug study and the need to comply with contraception instructions as directed by the investigator * Male participants are required to use a condom for study duration and until end of relevant systemic exposure defined as 7 months after the end of study treatment * Female partners of males participating in the study to consider use of effective methods of contraception until the end of relevant systemic exposure, defined as 7 months after the end of treatment in the male participant * Male participants with a pregnant or breastfeeding partner must agree to remain abstinent from penile vaginal intercourse or use a male condom during each episode of penile penetration during the treatment and until 7 months after the end of study treatment * Refrain from donating sperm for the duration of the study treatment and until 7 months after the end of study treatment * Confirmed azoospermic males are exempt from contraceptive requirements
• POST-SURGICAL IMMUNOTHERAPY: ECOG performance status 0-1
• POST-SURGICAL IMMUNOTHERAPY: White blood cell count >= 2,000 cells/mm^3
• POST-SURGICAL IMMUNOTHERAPY: Absolute lymphocyte count >= 500 cells/mm^3
• POST-SURGICAL IMMUNOTHERAPY: Absolute neutrophil count >= 1,000 cells/mm^3
• POST-SURGICAL IMMUNOTHERAPY: Hemoglobin >= 8 g/dL * Transfusion to achieve this level is not permitted within 2 weeks of cycle 1 day 1 of immunotherapy
• POST-SURGICAL IMMUNOTHERAPY: Platelets >= 80,000 cells/mm^3 * Transfusion to achieve this level is not permitted within 2 weeks of cycle 1 day 1 of immunotherapy
• POST-SURGICAL IMMUNOTHERAPY: AST and ALT =< 3 x ULN
• POST-SURGICAL IMMUNOTHERAPY: Total bilirubin =< 1.5 x ULN * Subjects with Gilbert syndrome may proceed as long as total bilirubin < 3.0 mg/dL
• POST-SURGICAL IMMUNOTHERAPY: Serum creatinine < 1.5 x ULN or creatinine clearance (CrCl) > 40 mL/min (measured using the Cockcroft-Gault formula)
• POST-SURGICAL IMMUNOTHERAPY: Patients must inform any and all partner(s) of their participation in a clinical drug study and the need to comply with contraception instructions as directed by the investigator
• POST-SURGICAL IMMUNOTHERAPY: Female patient of childbearing potential (WOCBP) (defined below) must have a negative urine or serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of study treatment). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required to be shown as negative for the patient to be eligible. If a patient has a positive serum pregnancy test, then an ultrasound must be done to rule out pregnancy to continue on trial * A woman is considered of childbearing potential (WOCBP) following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy * Women in the following categories are not considered WOCBP: ** Pre-menarchal ** Pre-menopausal female with one of the following: *** Documented hysterectomy *** Documented bilateral salpingectomy or tubal ligation *** Documented bilateral oophorectomy ** Postmenopausal female - A postmenopausal state is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes. In addition, females under the age of 55 years must have a serum follicle stimulating hormone, (FSH) level > 40 mIU/mL to confirm menopause
• POST-SURGICAL IMMUNOTHERAPY: WOCBP must be willing to use one of the highly effective methods of contraception (which have a failure rate of < 1% when used consistently and correctly) listed here during study duration and until the end of relevant systemic exposure, starting with visit 1 through 5 months after the end of study treatment. Approved contraceptive methods include combined (estrogen- and progestogen-containing) hormonal contraception (oral, intravaginal, transdermal), progestogen-only hormonal contraception (oral, injectable), implantable progestogen-only hormonal contraception, other hormonal methods of contraception (vaginal ring, injectables, implants and intrauterine hormone-releasing system), intrauterine device and bilateral tubal occlusion. A vasectomized partner is a highly effective contraception method provided that the partner is the sole male sexual partner of the WOCBP and the absence of sperm has been confirmed. If not, an additional highly effective method of contraception should be used. Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drug. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant. It is not necessary to use any other method of contraception when complete abstinence is elected. WOCBP participants who choose complete abstinence must continue to have pregnancy tests. Acceptable alternate methods of highly effective contraception must be discussed in the event that the WOCBP participants chooses to forego complete abstinence. The following are unacceptable methods of contraception: * Male or female condom with or without spermicide. Male and female condoms cannot be used simultaneously * Diaphragm with spermicide * Cervical cap with spermicide * Vaginal sponge with spermicide * Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mechanism of action * Periodic abstinence (calendar, symptothermal, post-ovulation methods) * Withdrawal (coitus interruptus). * Spermicide only * Lactation amenorrhea method (LAM)
• POST-SURGICAL IMMUNOTHERAPY: Male participants with female partners of childbearing potential are eligible to participate if they agree to the following during the treatment and until the end of relevant systemic exposure * Inform any and all partner(s) of their participation in a clinical drug study and the need to comply with contraception instructions as directed by the investigator * Male participants are required to use a condom for study duration and until end of relevant systemic exposure defined as 7 months after the end of study treatment * Female partners of males participating in the study to consider use of effective methods of contraception until the end of relevant systemic exposure, defined as 7 months after the end of treatment in the male participant * Male participants with a pregnant or breastfeeding partner must agree to remain abstinent from penile vaginal intercourse or use a male condom during each episode of penile penetration during the treatment and until 7 months after the end of study treatment * Refrain from donating sperm for the duration of the study treatment and until 7 months after the end of study treatment * Confirmed azoospermic males are exempt from contraceptive requirements

Exclusion Criteria

• Patients cannot have had any prior therapy for the locally advanced pancreatic adenocarcinoma prior to signing informed consent form * Patients will be allowed to enroll on trial up to one month after initiating the standard of care (SOC) FOLFIRINOX (FFX) described in this study as long as all other eligibility criteria have been met
• Patients with a history of past treatment with immunotherapy agents prior to initial enrollment into this study (including, but not limited to: IL-2, interferon, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, anti-CTLA-4 or anti-CCR2/5 antibodies)
• Patients with prior organ or tissue allograft, including corneal allograft, or allogeneic bone marrow transplantation. Exceptions can be approved by the Investigational New Drug (IND) Sponsor if loss of the graft is not a clinical concern
• Is currently participating or has participated in a study of an investigational agent or using an investigational device for the treatment of cancer. The principal investigator must approve the patient’s participation in other clinical trials
• History of any autoimmune disease, including any history of inflammatory bowel disease, including ulcerative colitis and Crohn’s disease, as well as history of symptomatic disease (e.g. rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener’s Granulomatosis]); central nervous system (CNS) or motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and myasthenia gravis, multiple sclerosis). Patients with thyroid disease will be allowed. Autoimmune diagnoses not listed here must be approved by the principal investigator
• Known history of interstitial lung disease, has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
• Requires the use of home oxygen
• Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following: * Myocardial infarction or stroke/transient ischemic attack within the past 6 months * Uncontrolled angina within the past 3 months * Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes) * History of other clinically significant heart disease (e.g., cardiomyopathy, congestive heart failure with New York Heart Association functional classification III-IV, pericarditis, significant pericardial effusion, or myocarditis) * Cardiovascular disease-related requirement for daily supplemental oxygen therapy
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome
• History of any chronic hepatitis as evidenced by the following: * Positive test for hepatitis B surface antigen * Positive test for qualitative hepatitis C viral load (by polymerase chain reaction [PCR]) * Note: Participants with positive hepatitis C antibody and negative quantitative hepatitis C by PCR are eligible. History of resolved hepatitis A virus infection is not an exclusion criterion
• Any concurrent malignancy other than non-melanoma skin cancer, noninvasive bladder cancer, early stage prostate cancer, or carcinoma in situ of the cervix. Patients with a previous non-pancreatic, non-periampullary malignancy without evidence of disease for > 2 years will be allowed to enter the trial
• Other uncontrolled intercurrent illness including, but not limited to, chronic ongoing infection or psychiatric illness/social situations that would limit compliance with study requirements
• Current or recent (within 3 months of study treatment administration) gastrointestinal disease that could impact the absorption of study treatment
• Any gastrointestinal surgery that is likely impact upon the absorption of study treatment
• Inability to be venipunctured and/or tolerate venous access
• Ascites needing paracentesis or medical management
• History of severe hypersensitivity reaction to any monoclonal antibody
• History of allergy to study treatments or any of its components of the study arm that participant is enrolling
• Patient has a known or suspected hypersensitivity to GM-CSF, hetastarch, corn, dimethyl sulfoxide, fetal bovine serum, trypsin (porcine origin), yeast or any other component of GVAX pancreas vaccine
• Women who are pregnant or breastfeeding
• Patient is unwilling or unable to follow the study schedule for any reason
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Any anti-neoplastic biologics, vaccines or hormonal treatment, including investigational drugs, within 28 days of the first dose of study combination immunotherapy administration
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Is currently participating or has participated in a study of an investigational agent or using an investigational device for the treatment of cancer. The patient’s participation in other clinical trials must be approved by the principal investigator
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Patients receiving active immunosuppressive agents and chronic use of systemic corticosteroids within 14 days of the first dose of study combination immunotherapy administration
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Patients who have received a live vaccine within 28 days of the first dose of study immunotherapy administration. Examples of live vaccine include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, BCG, and typhoid vaccine * Note: Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed. However, intranasal influenza vaccines (e.g. Flu-Mist) are live-attenuated vaccines, and are not allowed within 28 days of study treatment
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Patients receiving growth factors including, but not limited to, granulocyte colony stimulating factor (G-CSF), GM-CSF, erythropoietin, within 14 days of the first dose of study immunotherapy administration. Use of such agents while on study is also prohibited
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Any evidence of metastatic disease by radiologic imaging
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Has a pulse oximetry < 92% on room air
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Requires the use of home oxygen
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following: * Myocardial infarction or stroke/transient ischemic attack within the past 6 months * Uncontrolled angina within the past 3 months * Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes) * History of other clinically significant heart disease (e.g., cardiomyopathy, congestive heart failure with New York Heart Association functional classification III-IV, pericarditis, significant pericardial effusion, or myocarditis) * Cardiovascular disease-related requirement for daily supplemental oxygen therapy
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Evidence of uncontrolled, active infection, requiring parenteral anti-bacterial, anti-viral or anti-fungal therapy < 7 days prior to administration of study immunotherapy treatment
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Other uncontrolled intercurrent illness including, but not limited to, chronic ongoing infection or psychiatric illness/social situations that would limit compliance with study requirements
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Current or recent (within 3 months of study treatment administration) gastrointestinal disease that could impact the absorption of study treatment
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Any gastrointestinal surgery that is likely impact upon the absorption of study treatment
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Inability to be venipunctured and/or tolerate venous access
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Patients who have had surgery within 28 days of the first dose of study combination immunotherapy administration, excluding minor procedures (dental work, skin biopsy, etc.), duodenal stent placement, celiac plexus block, vascular access devices and biliary stent placement. Participants must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before the first dose of study immunotherapy treatment
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Current or prior use of strong/moderate CYP3A4 inhibitors or inducers within 28 days of the first dose of BMS-813160. These agents are also not allowed while the patient is on study
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Current or prior use of class I antiarrhythmics (eg, quinidine, procainamide, disopyramide, lidocaine, phenytoin, mexiletine, tocainide, flecainide, propafenone, and moricizine) within 28 days of the first dose of BMS-813160
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Current use of tricyclic antidepressants
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Ascites needing paracentesis or medical management
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Any of the following on 12-lead electrocardiogram (ECG) prior to study treatment administration, confirmed by repeat * QRS >= 120 msec, except right bundle branch block * QTcF (QT corrected for heart rate using Fridericia's method) >= 480 msec, except right bundle branch block
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: History of severe hypersensitivity reaction to any monoclonal antibody.
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: History of allergy to study treatments or any of its components of the study arm that participant is enrolling
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Patient has a known or suspected hypersensitivity to GM-CSF, hetastarch, corn, dimethyl sulfoxide, fetal bovine serum, trypsin (porcine origin), yeast or any other component of GVAX pancreas vaccine
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Women who are pregnant or breastfeeding
• CONTINUATION IN STUDY AND INITIATION OF IMMUNOTHERAPY: Patient is unwilling or unable to follow the study schedule for any reason
• POST-SURGICAL IMMUNOTHERAPY: Any anti-neoplastic biologics, vaccines or hormonal treatment, including investigational drugs, within 28 days of the first dose of study combination immunotherapy administration
• POST-SURGICAL IMMUNOTHERAPY: Patients with a history of past treatment with immunotherapy agents prior to initial enrollment into this study (including, but not limited to: IL-2, interferon, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, anti-CTLA-4 or anti-CCR2/5 antibodies)
• POST-SURGICAL IMMUNOTHERAPY: Is currently participating or has participated in a study of an investigational agent or using an investigational device for the treatment of cancer. The patient’s participation in other clinical trials must be approved by the principal investigator
• POST-SURGICAL IMMUNOTHERAPY: Patients receiving active immunosuppressive agents and chronic use of systemic corticosteroids within 14 days of the first dose of study combination immunotherapy administration
• POST-SURGICAL IMMUNOTHERAPY: Patients who have received any prophylactic vaccine within 14 days of the first dose of study immunotherapy administration or received a live vaccine within 28 days of the first dose of study immunotherapy administration. Examples of live vaccine include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, BCG, and typhoid vaccine. * Note: Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed. However, intranasal influenza vaccines (e.g. Flu-Mist) are live-attenuated vaccines, and are not allowed within 28 days of study treatment.
• POST-SURGICAL IMMUNOTHERAPY: Patients receiving growth factors including, but not limited to, granulocytecolony stimulating factor (G-CSF), GM-CSF, erythropoietin, within 14 days of the first dose of study immunotherapy administration. Use of such agents while on study is also prohibited
• POST-SURGICAL IMMUNOTHERAPY: Any evidence of metastatic disease by radiologic imaging
• POST-SURGICAL IMMUNOTHERAPY: Has a pulse oximetry < 92% on room air
• POST-SURGICAL IMMUNOTHERAPY: Requires the use of home oxygen
• POST-SURGICAL IMMUNOTHERAPY: Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following: * Myocardial infarction or stroke/transient ischemic attack within the past 6 months * Uncontrolled angina within the past 3 months * Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes) * History of other clinically significant heart disease (eg, cardiomyopathy, congestive heart failure with New York Heart Association functional classification III-IV, pericarditis, significant pericardial effusion, or myocarditis) * Cardiovascular disease-related requirement for daily supplemental oxygen therapy
• POST-SURGICAL IMMUNOTHERAPY: Evidence of uncontrolled, active infection, requiring parenteral anti-bacterial, anti-viral or anti-fungal therapy < 7 days prior to administration of study immunotherapy treatment
• POST-SURGICAL IMMUNOTHERAPY: Other uncontrolled intercurrent illness including, but not limited to, chronic ongoing infection or psychiatric illness/social situations that would limit compliance with study requirements
• POST-SURGICAL IMMUNOTHERAPY: Current or recent (within 3 months of study treatment administration) gastrointestinal disease that could impact the absorption of study treatment
• POST-SURGICAL IMMUNOTHERAPY: Any gastrointestinal surgery that is likely impact upon the absorption of study treatment
• POST-SURGICAL IMMUNOTHERAPY: Inability to be venipunctured and/or tolerate venous access
• POST-SURGICAL IMMUNOTHERAPY: Patients who have had surgery within 28 days of the first dose of study combination immunotherapy administration, excluding minor procedures (dental work, skin biopsy, etc.), duodenal stent placement, celiac plexus block, vascular access devices and biliary stent placement. Participants must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before the first dose of study immunotherapy treatment.
• POST-SURGICAL IMMUNOTHERAPY: Current or prior use of strong/moderate CYP3A4 inhibitors or inducers within 28 days or 5 half-lives, whichever is shorter, prior to the first dose of BMS-813160
• POST-SURGICAL IMMUNOTHERAPY: Current or prior use of Class I antiarrhythmics (eg, quinidine, procainamide, dysopiramide, lidocaine, phenytoin, mexiletine, tocainide, flecainide, propafenone, and moricizine) within 28 days of the first dose of BMS-813160
• POST-SURGICAL IMMUNOTHERAPY: Current use of tricyclic antidepressants
• POST-SURGICAL IMMUNOTHERAPY: Ascites needing paracentesis or medical management
• POST-SURGICAL IMMUNOTHERAPY: Any of the following on 12-lead electrocardiogram (ECG) prior to study treatment administration, confirmed by repeat. * QRS >= 120 msec, except right bundle branch block * QTcF (QT corrected for heart rate using Fridericia's method) >= 480 msec, except right bundle branch block
• POST-SURGICAL IMMUNOTHERAPY: History of severe hypersensitivity reaction to any monoclonal antibody
• POST-SURGICAL IMMUNOTHERAPY: History of allergy to study treatments or any of its components of the study arm that participant is enrolling
• POST-SURGICAL IMMUNOTHERAPY: Patient has a known or suspected hypersensitivity to GM-CSF, hetastarch, corn, dimethyl sulfoxide, fetal bovine serum, trypsin (porcine origin), yeast or any other component of GVAX pancreas vaccine
• POST-SURGICAL IMMUNOTHERAPY: Women who are pregnant or breastfeeding
• POST-SURGICAL IMMUNOTHERAPY: Patient is unwilling or unable to follow the study schedule for any reason