Trial Outcomes & Findings for Immune Checkpoint Inhibition (Tremelimumab and/or MEDI4736) in Combination With Radiation Therapy in Patients With Unresectable Pancreatic Cancer (NCT NCT02311361)

Last Updated: 2021-04-20

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

65 participants

Primary outcome timeframe

Participants were assessed from the start of study treatment at Cycle 1 then after every cycle (1 cycle = 28 days) of protocol treatment until 30 days after they were taken off treatment, approximately 4.0 months.

Results posted on

2021-04-20

Participant Flow

Participant milestones

Participant milestones
Measure	Durvalumab + 8 Gray (Gy) in 1 Fraction 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 +5 Gy in 5 Fractions 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 +Tremelimumab + 8 Gy in 1 Fraction 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 +5 Gy in 5 Fractions 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
Overall Study STARTED	14	11	19	21
Overall Study Received Radiation Therapy Only	0	1	1	1
Overall Study COMPLETED	14	10	19	20
Overall Study NOT COMPLETED	0	1	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Durvalumab + 8 Gray (Gy) in 1 Fraction 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 +5 Gy in 5 Fractions 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 +Tremelimumab + 8 Gy in 1 Fraction 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 +5 Gy in 5 Fractions 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
Overall Study Did not receive treatment	0	1	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Durvalumab + 8 Gray (Gy) in 1 Fraction n=14 Participants 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 +5 Gy in 5 Fractions n=11 Participants 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 +Tremelimumab + 8 Gy in 1 Fraction n=19 Participants 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 +5 Gy in 5 Fractions n=21 Participants 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	Total n=65 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants	12 Participants n=4 Participants	41 Participants n=21 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	9 Participants n=4 Participants	24 Participants n=21 Participants
Age, Continuous	61.75 years STANDARD_DEVIATION 9.27 • n=5 Participants	61.70 years STANDARD_DEVIATION 6.36 • n=7 Participants	64.26 years STANDARD_DEVIATION 11.77 • n=5 Participants	65.31 years STANDARD_DEVIATION 9.58 • n=4 Participants	63.26 years STANDARD_DEVIATION 9.25 • n=21 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants	4 Participants n=4 Participants	25 Participants n=21 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants	17 Participants n=4 Participants	40 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	14 Participants n=5 Participants	11 Participants n=7 Participants	18 Participants n=5 Participants	21 Participants n=4 Participants	64 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants	8 Participants n=21 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants	11 Participants n=7 Participants	16 Participants n=5 Participants	17 Participants n=4 Participants	55 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Region of Enrollment United States	14 Participants n=5 Participants	11 Participants n=7 Participants	19 Participants n=5 Participants	21 Participants n=4 Participants	65 Participants n=21 Participants

PRIMARY outcome

Timeframe: Participants were assessed from the start of study treatment at Cycle 1 then after every cycle (1 cycle = 28 days) of protocol treatment until 30 days after they were taken off treatment, approximately 4.0 months.

Outcome measures

Outcome measures
Measure	Cohort A Dose Level A1 n=14 Participants 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 A2 n=10 Participants 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 C Dose Level C1 n=19 Participants 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 C2 n=20 Participants 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
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Pruritis	1 Adverse events	1 Adverse events	2 Adverse events	3 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Rash maculo-papular	0 Adverse events	1 Adverse events	1 Adverse events	2 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Dizziness	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Abdominal pain	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Alanine aminotransferase increased	1 Adverse events	0 Adverse events	0 Adverse events	5 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Alkaline Phosphatase increased	0 Adverse events	2 Adverse events	0 Adverse events	2 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Anemia	3 Adverse events	3 Adverse events	9 Adverse events	9 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Anorexia	1 Adverse events	0 Adverse events	0 Adverse events	3 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Atrial fibrillation	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Aspartate aminotransferase increased	1 Adverse events	0 Adverse events	1 Adverse events	6 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Back pain	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Blood bilirubin increased	0 Adverse events	0 Adverse events	1 Adverse events	1 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Cough	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Creatinine increased	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Diarrhea	0 Adverse events	1 Adverse events	1 Adverse events	7 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Dry mouth	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Dysgeusia	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Endocrine disorders,Other, Elevated T3, T4	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Eye disorders - decr. in near vision,bilat	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 - Fatigue	1 Adverse events	2 Adverse events	0 Adverse events	7 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Fever	1 Adverse events	1 Adverse events	1 Adverse events	1 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Headache	0 Adverse events	2 Adverse events	0 Adverse events	0 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Hemorrhoidal hemorrhage	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Hoarseness	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Hyperglycemia	0 Adverse events	0 Adverse events	2 Adverse events	0 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 - Hyperkalemia	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Hyperuricemia	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Hypoalbuminemia	0 Adverse events	0 Adverse events	0 Adverse events	5 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Hypocalcemia	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 - Hyponatremia	2 Adverse events	0 Adverse events	3 Adverse events	4 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Hypothyroidism	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Infusion related reaction	0 Adverse events	0 Adverse events	0 Adverse events	2 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Lymphocyte count decreased	15 Adverse events	20 Adverse events	17 Adverse events	26 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Mucositis	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Musculoskeletal & connective tissue	0 Adverse events	3 Adverse events	0 Adverse events	0 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Nausea	0 Adverse events	1 Adverse events	3 Adverse events	2 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Neutrophil count decreased	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Pain	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Platelet count decreased	2 Adverse events	0 Adverse events	7 Adverse events	13 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Serum amylase increased	0 Adverse events	0 Adverse events	0 Adverse events	3 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 - Skin/subc tissue disorder - Night sweats	0 Adverse events	0 Adverse events	1 Adverse events	1 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Skin/subc tissue disorder - Rash	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Skin/subc tissue - Psoriasis	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Skin/subc tissue disorder - Itching	0 Adverse events	1 Adverse events	1 Adverse events	0 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Skin/subc tissue disorder-Skinpeeling hand	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Vertigo	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Vomiting	0 Adverse events	0 Adverse events	1 Adverse events	4 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 Weight loss	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 1 White blood cell decreased	1 Adverse events	4 Adverse events	1 Adverse events	7 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 2 Abdominal pain	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 2 Anemia	3 Adverse events	1 Adverse events	9 Adverse events	10 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 2 Anorexia	0 Adverse events	0 Adverse events	0 Adverse events	2 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 2 Autoimmune disorder	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 2 Diarrhea	0 Adverse events	1 Adverse events	2 Adverse events	4 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 2 Dysgeusia	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 2 Endocrine disorders - TSH elev-Hypothyroid	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 2 Fatigue	0 Adverse events	0 Adverse events	2 Adverse events	5 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 2 Fecal incontinence	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 2 Fever	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 2 Gastroesophageal reflux disease	0 Adverse events	1 Adverse events	0 Adverse events	0 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 2 Hyperglycemia	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 2 Hypoalbuminemia	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 2 Hypothyroidism	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 2 Hypophosphatemia	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 2 Infusion related reaction	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 2 Lymphocyte count decreased	7 Adverse events	19 Adverse events	15 Adverse events	30 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 2 Malaise	0 Adverse events	0 Adverse events	0 Adverse events	2 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 2 Nausea	0 Adverse events	0 Adverse events	0 Adverse events	3 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 2 Neutrophil count decreased	0 Adverse events	0 Adverse events	2 Adverse events	1 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 2 Platelet count decreased	0 Adverse events	0 Adverse events	1 Adverse events	2 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 2 Rash maculo-papular	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 2 Weight loss	0 Adverse events	0 Adverse events	0 Adverse events	2 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 2 White blood cell count	0 Adverse events	2 Adverse events	1 Adverse events	0 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 3 Anemia	0 Adverse events	0 Adverse events	2 Adverse events	3 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 3 Anorexia	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 3 Colitis	0 Adverse events	0 Adverse events	0 Adverse events	2 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 3 Dehydration	0 Adverse events	0 Adverse events	0 Adverse events	3 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 3 Diarrhea	0 Adverse events	0 Adverse events	0 Adverse events	3 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 3 Fatigue	0 Adverse events	0 Adverse events	1 Adverse events	1 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 3 Hyperthyroidism	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 3 Lymphocyte count decreased	3 Adverse events	7 Adverse events	6 Adverse events	18 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 3 Nausea	0 Adverse events	0 Adverse events	0 Adverse events	2 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 3 Serum amylase increased	0 Adverse events	0 Adverse events	1 Adverse events	0 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 3 Vomiting	0 Adverse events	0 Adverse events	0 Adverse events	2 Adverse events
Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug Grade 4 Lymphocyte count decreased	0 Adverse events	0 Adverse events	2 Adverse events	2 Adverse events

SECONDARY outcome

Timeframe: 30 days after treatment

Population: The pharmacokinetic studies were not done since the company were not interested in this after the samples were collected

Drug level in blood

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 month

Participants who survived at least 6 months after therapy.

Outcome measures

Outcome measures
Measure	Cohort A Dose Level A1 n=14 Participants 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 A2 n=10 Participants 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 C Dose Level C1 n=19 Participants 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 C2 n=20 Participants 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
Percentage of Participants With 6-month Overall Survival	26 percentage of participants	58 percentage of participants	12 percentage of participants	40 percentage of participants

SECONDARY outcome

Timeframe: From study entry to death or date of last contact, whichever occurs first, up to 2 years of follow-up

Amount of time participants survived after therapy.

Outcome measures

Outcome measures
Measure	Cohort A Dose Level A1 n=14 Participants 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 A2 n=10 Participants 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 C Dose Level C1 n=19 Participants 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 C2 n=20 Participants 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
Overall Survival	3.3 Months Interval 1.2 to 6.6	9.0 Months Interval 0.5 to 18.4	2.1 Months Interval 1.1 to 4.3	4.2 Months Interval 2.9 to 9.3

SECONDARY outcome

Timeframe: At screening then every 8 weeks until disease progression or patient is taken off the trial, whichever comes first, approximately 6 months.

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.

Outcome measures

Outcome measures
Measure	Cohort A Dose Level A1 n=14 Participants 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 A2 n=10 Participants 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 C Dose Level C1 n=19 Participants 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 C2 n=20 Participants 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
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) Complete Response	0 Participants	0 Participants	0 Participants	0 Participants
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) Partial Response	1 Participants	0 Participants	0 Participants	1 Participants
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) Stable Disease	3 Participants	4 Participants	2 Participants	5 Participants
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) Progressive Disease	4 Participants	4 Participants	6 Participants	10 Participants

SECONDARY outcome

Timeframe: From study entry to disease progression, death or date of last contact, whichever occurs first, an average of 6 months

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.

Outcome measures

Outcome measures
Measure	Cohort A Dose Level A1 n=14 Participants 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 A2 n=10 Participants 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 C Dose Level C1 n=19 Participants 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 C2 n=20 Participants 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
Progression Free Survival (PFS)	1.7 Months Interval 0.8 to 2.0	2.5 Months Interval 0.1 to 3.7	0.9 Months Interval 0.7 to 2.1	2.3 Months Interval 1.9 to 3.4

SECONDARY outcome

Timeframe: Date treatment consent signed to date off study, approximately 18 months and 4 days for Cohort 1/Dose Level A1, 23 months and 29 days for Cohort 2/Dose Level A2, 32 months and 19 days for Cohort C/Dose Level C1, and 44 months and 18 days for Cohort C/Dose

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.

Outcome measures

Outcome measures
Measure	Cohort A Dose Level A1 n=14 Participants 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 A2 n=11 Participants 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 C Dose Level C1 n=19 Participants 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 C2 n=20 Participants 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
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)	14 Participants	10 Participants	19 Participants	20 Participants

Adverse Events

Durvalumab + 8 Gray (Gy) in 1 Fraction

Serious events: 6 serious events

Other events: 14 other events

Deaths: 14 deaths

Durvalumab +5 Gy in 5 Fractions

Serious events: 2 serious events

Other events: 10 other events

Deaths: 8 deaths

Durvalumab +Tremelimumab + 8 Gy in 1 Fraction

Serious events: 11 serious events

Other events: 19 other events

Deaths: 2 deaths

Durvalumab +Tremelimumab +5 Gy in 5 Fractions

Serious events: 12 serious events

Other events: 20 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Tim Greten

National Cancer Institute

Phone: 240-760-6114

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place