Cohort 1/Dose Level A1 Durvalumab + 8 Gray (Gy) in 1 fraction

Cohort 2/Dose Level A2 Durvalumab +5 Gy in 5 fractions

Cohort 3/Dose Level B1 (was removed with Amendment A) Tremelimumab + 8 Gy in 1 fraction

Cohort 4/Dose Level B2 (was removed with Amendment A) Tremelimumab + 5 Gy in 5 fractions

Cohort C/ Dose Level C1 Durvalumab +Tremelimumab + 8 Gy in 1 fraction

Cohort C/Dose Level C2 Durvalumab +Tremelimumab +5 Gy in 5 fractions

Cohort 1/Dose Level A1 Durvalumab + 8 Gray (Gy) in 1 fraction
Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks.
Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5

Durvalumab + 8 Gray (Gy) in 1 Fraction

Cohort 2/Dose Level A2 Durvalumab +5 Gy in 5 fractions
Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks.
Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5

Durvalumab +5 Gy in 5 Fractions

Cohort C/ Dose Level C1 Durvalumab +Tremelimumab + 8 Gy in 1 fraction
Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks.
Tremelimumab: 75 mg IV, every 4 weeks for 16 weeks
Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5

Durvalumab +Tremelimumab + 8 Gy in 1 Fraction

Cohort C/Dose Level C2 Durvalumab +Tremelimumab +5 Gy in 5 fractions
Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks.
Tremelimumab: 75 mg IV, every 4 weeks for 16 weeks
Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5

Durvalumab +Tremelimumab +5 Gy in 5 Fractions

Total

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Region of Enrollment

Adverse Events (AEs) are reported by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade 1=Mild, Grade 2= Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Fatal.

Durvalumab + 8 Gray (Gy) in 1 fraction
Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks.
Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5

Cohort A Dose Level A1

Durvalumab +5 Gy in 5 fractions
Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks.
Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5

Cohort A Dose Level A2

Durvalumab +Tremelimumab + 8 Gy in 1 fraction
Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks.
Tremelimumab: 75 mg IV, every 4 weeks for 16 weeks
Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5

Cohort C Dose Level C1

Durvalumab +Tremelimumab +5 Gy in 5 fractions
Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks.
Tremelimumab: 75 mg IV, every 4 weeks for 16 weeks
Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5

Cohort C Dose Level C2

Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug

Plasma Pharmacokinetic (PK)

Participants who survived at least 6 months after therapy.

Percentage of Participants With 6-month Overall Survival

Amount of time participants survived after therapy.

Overall Survival

Progressive disease (PD): >=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started. Complete response (CR): disappearance of all target lesions. Partial response (PR): >=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD. Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD.

Tumor Response Assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as Measured by Computed Tomography (CT) and Magnetic Resonance Imaging (MRI)

PFS is the defined as the median amount of time subject survives without disease progression after treatment. Progression is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). NOTE: While RECIST Progressive Disease (PD) will be noted and recorded the immune-related (IR) RECIST criteria will be applied to determine discontinuation of study treatment. For modified Immune-Related Response Criteria (irRC), only target and measurable lesions are taken into account.

Progression Free Survival (PFS)

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)

Overall Study

Dr. Tim Greten

Pancreatic Neoplasms

Pancreatic Cancer

Cancer of Pancreas

Cancer of the Pancreas

Pancreas Cancer

10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks.

Durvalumab

Tremelimumab

Sterostatic body radiation therapy (SBRT)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Immune Checkpoint Inhibition (Tremelimumab and/or MEDI4736) in Combination With Radiation Therapy in Patients With Unresectable Pancreatic Cancer

A Pilot Study of Immune Checkpoint Inhibition (Durvalumab With or Without Tremelimumab) in Combination With Radiation Therapy in Patients With Unresectable Pancreatic Cancer

Tim Greten, M.D.

Principal Investigator

National Cancer Institute (NCI)

Celiac Disease

Celiac Sprue

Gluten Enteropathy

Gluten-Sensitive Enteropathy

Hu-Mik-Beta-1 every 3 weeks for a total of 3 doses (given on day 1, week 3 and week 6)

Hu-Mik- Beta-1

Mayo Clinic, Rochester

Antibody Treatment for Advanced Celiac Disease

Phase I Study of the Humanized Mik-Beta-1 Monoclonal Antibody Directed Toward IL-2/IL-15R Beta (CD122) That Blocks IL-15 Action In Patients With Refractory Celiac Disease

Events will be tabulated and reported by grade with evaluationalso of supportive medications and surrogate markers of absorptionsuch as body mass index, albumin and hemoglobin.

Mayo Clinic

Following a screening evaluation, participants will receive two infusions of tocilizumab, one at baseline and another at week 4 of the study. All subjects will receive a 4 mg/kg infusion of tocilizumab, the recommended starting dose for adults with rheumatoid arthritis.

Following a screening evaluation, participants will receive two infusions of tocilizumab, one at baseline and another at week 4 of the study. All subjects will receive a 4 mg/kg infusion of tocilizumab, the recommended starting dose for adults with rheumatoid arthritis.
Tocilizumab: Therapeutic/Pharmacologic Class of Drug:
Tocilizumab is a recombinant humanized anti-human interleukin-6 (IL-6) receptor monoclonal antibody of the immunoglobulin (Ig) gamma-1 subclass.
Type of Dosage Form:
Concentrate for solution for infusion.
Route of Administration:
Intravenous (i.v.) infusion.

Tocilizumab

The Brief Assessment of Cognition in Schizophrenia (BACS) is the metric used to characterize cognition in this study. The BACS consists of 6 subscales: Verbal Memory (range 0-75), Working Memory (range 0-28), Motor Speed (range 0-100), Verbal Fluency (measure is total number of words generated in two 60 second trials), Attention and Processing speed (range 0-110), and Executive Function (range 0-22). For each subscale, higher scores reflect better cognition. For each subscale, a Standard Deviation Score was calculated based on normative data (Keefe et al. Norms and standardization of the Brief Assessment of Cognition in Schizophrenia (BACS). Schizophrenia Research 102 (2008) 108-115). The BACS composite score is calculated as the average Standard Deviation Score of the 6 subscale scores. The change in BACS composite score was calculated as the BACS composite score at 8 weeks minus the BACS composite score at baseline.

Change in Cognition

The Positive and Negative Symptoms Scale (PANSS) is the metric used to characterize psychotic symptoms in this study. The PANSS consists of 30 items, each scored 1-7. The range for the PANSS total score is 30-210. There are 3 subscales - PANSS positive score (range 7-49), PANSS negative score (range 7-49), and PANSS general score (range 16-112). PANSS total score is the summation of these 3 subscales. Higher values for the total and subscale scores reflect more severe psychopathology. A positive change in PANSS total score reflects an increase in psychopathology. A negative change in PANSS total score reflects a decrease in psychopathology.

Change in Total Psychotic Symptoms

Following a screening evaluation, participants will receive two infusions of Tocilizumab, one at baseline and another at week 4 of the study. All subjects will receive a 4 mg/kg infusion of Tocilizumab, the recommended starting dose for adults with rheumatoid arthritis.
Tocilizumab: Therapeutic/Pharmacological Class of Drug:
Tocilizumab is a recombinant humanized anti-human interleukin-6 (IL-6) receptor monoclonal antibody of the immunoglobulin (Ig) gamma-1 subclass.
Type of Dosage Form:
Concentrate for solution for infusion.
Route of Administration:
Intravenous (i.v.) infusion.

Dr. Brian Miller

Schizophrenia

Therapeutic/Pharmacologic Class of Drug:
Tocilizumab is a recombinant humanized anti-human interleukin-6 (IL-6) receptor monoclonal antibody of the immunoglobulin (Ig) gamma-1 subclass.
Type of Dosage Form:
Concentrate for solution for infusion.
Route of Administration:
Intravenous (i.v.) infusion.

diverticulitis/diarrhea

Immune Checkpoint Inhibition (Tremelimumab and/or MEDI4736) in Combination With Radiation Therapy in Patients With Unresectable Pancreatic Cancer

Antibody Treatment for Advanced Celiac Disease

An Open-Label Trial of Tocilizumab in Schizophrenia

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