FOLFIRINOX Followed by Ipilimumab With Pancreatic Tumor Vaccine in Treatment of Metastatic Pancreatic Cancer

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Completed
• CT.gov ID: NCT01896869
• Collaborator: (none)
• Enrollment: 83
• Locations: 3
• Arms: 2
• Actual Duration (Months): 66
• Patients Per Site: 27.7
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This study will enroll patients who have metastatic pancreatic cancer with stable disease on FOLFIRINOX chemotherapy. The main purpose of this study is to compare survival between patients that receive ipilimumab and a pancreatic tumor vaccine and patients who continue to receive FOLFIRINOX.

Funding Source - FDA Office of Orphan Product Development (OOPD)

Condition or Disease	Intervention/Treatment	Phase
Metastatic Pancreatic Adenocarcinoma	Drug: Ipilimumab; Biological: Vaccine; Drug: FOLFIRINOX	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 83 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Multicenter Study of FOLFIRINOX Followed by Ipilimumab in Combination With Allogeneic GM-CSF Transfected Pancreatic Tumor Vaccine in the Treatment of Metastatic Pancreatic Cancer
• Actual Study Start Date: Nov 1, 2013
• Actual Primary Completion Date: May 3, 2019
• Actual Study Completion Date: May 3, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ipilimumab + Vaccine (Arm A) Ipilimumab and vaccine will be administered every 3 weeks for 4 doses, then every 8 weeks.	Drug: Ipilimumab; 3 mg/kg administered IV (10mg/kg if treatment started prior to protocol v 6.3); Other Names: MDX-010 BMS-734016 ; Biological: Vaccine; 5x10^8 cells administered in 6 intradermal injections; Other Names: PANC 6.03 pcDNA-1/GM-Neo and PANC 10.05 pcDNA-1/GM-Neo Allogeneic GM-CSF-Transduced Pancreatic Tumor Cell Vaccine (GVAX)
Experimental: FOLFIRINOX (Arm B) Administered every 14 days (one cycle)	Drug: FOLFIRINOX; Standard of care FOLFIRINOX may be modified according to the patient's known tolerability. Acceptable modified options could include 5-FU alone, capecitabine, FOLFOX, FOLFIRI, or FOLFIRINOX on a 21 day cycle.

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) [4 years]

   Overall Survival is the time between the date of randomization on study and death.

Secondary Outcome Measures

1. Toxicity of Ipilimumab in Combination With Pancreatic Tumor Vaccine [From the first dose of study drug through 70 days after last dose, up to 13 months]

   Toxicity was assessed as the number of patients experiencing study drug-related adverse events (AEs). Data reported for only study drug-related adverse events (not all adverse events as reported in the adverse events section).

2. Progression Free Survival (PFS) [Up to 4 years]

   Progression Free Survival is the time from date of randomization to progression or death, whichever comes first. Individuals without follow-up scans were censored one day after randomization and individuals with follow-up scans who did not have disease progression were censored at date of last scan.

3. Immune-related Progression Free Survival (irPFS) [Up to 4 years]

   Immune-related Progression Free Survival is the median time from date of randomization to disease progression or death, whichever comes first. Individuals without follow-up scans were censored one day after randomization and individuals with follow-up scans who did not have disease progression were censored at date of last scan. Disease progression was evaluated using immune-related Response Criteria (irRC). irRC differs from RECIST primarily in that target lesions are measured in 2 dimensions and new lesions contribute to tumor burden, but do not by themselves qualify as progressive disease.

4. Objective Response Rate [Assessed until disease progression, up to 2 years]

   Objective Response Rate (ORR) is defined as the number of patients from each group achieving a Complete Response (CR) or Partial Response (PR) by Response Evaluation Criteria In Solid Tumors (RECIST).

5. Immune-related Objective Response Rate [Assessed until disease progression, up to 2 years]

   Immune-related Objective Response Rate (irORR) is measured the same way, except that tumor responses are evaluated using immune-related response criteria (irRC). irRC differs from RECIST primarily in that target lesions are measured in 2 dimensions and new lesions contribute to tumor burden, but do not by themselves qualify as progressive disease.

6. Duration of Response [Up to 22 months]

   Average length of time between achieving a complete response (CR) or partial response (PR) and documentation of recurrent or progressive disease.

7. Tumor Marker Kinetics as Assessed by Median Carbohydrate Antigen 19-9 (CA19-9) Levels [Baseline, Week 7, and Week 10 visits]

   Carbohydrate Antigen 19-9 (CA19-9) is a tumor marker measured in the blood of patients with pancreas cancer. Not all patients with pancreas cancer will have elevated CA19-9 and there are some conditions other than cancer that can cause an elevated CA19-9. Normal CA19-9 range is 0-36 U/mL.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria (abbreviated):

1. Documented adenocarcinoma of the pancreas

2. Stable metastatic pancreatic cancer after 8-12 doses of FOLFIRINOX

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

4. Life expectancy greater than 3 months

5. Adequate organ and marrow function defined by study-specified laboratory tests.

6. Must use acceptable form of birth control while on study

7. Oxygen saturation on room air >92%

Exclusion Criteria (abbreviated):

1. Surgery within 4 weeks of dosing investigational agent (some exceptions for minor procedures)

2. Off FOLFIRINOX treatment for more than 70 days prior to treatment on study

3. Prior chemotherapy for metastatic pancreatic cancer (other than FOLFIRINOX or adjuvant therapy).

4. History of prior treatment with ipilimumab, anti-PD1 antibody, CD137 agonist, or anti-CD40 antibody

5. Received any non-oncology live vaccine therapy up to one month prior to or after any dose of ipilimumab/vaccine

6. Receiving any other investigational agents

7. Any of the following concomitant therapy: IL-2, interferon, immunosuppressive agents, or chronic use of systemic corticosteroids

8. History of symptomatic autoimmune disease or immune impairment. Thyroid disease is allowed.

9. Known brain metastasis

10. Radiographic ascites that is apparent on physical exam or requiring intervention in the 2 months prior to enrollment

11. Uncontrolled intercurrent illness

12. Known or suspected hypersensitivity to GM-CSF

13. Chronic HIV, Hepatitis B or Hepatitis C

14. Pregnant or breastfeeding women

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California	United States	94143
2	The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21205
3	Washington University School of Medicine	Saint Louis	Missouri	United States	63110

Sponsors and Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Investigators

• Principal Investigator: Dung Le, M.D., The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 10, 2017

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT01896869
• Other Study ID Numbers: J13108; NA_00086350; FD-R-004819-01
• First Posted: Jul 11, 2013
• Last Update Posted: May 19, 2020
• Last Verified: Apr 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: Pancreatic Cancer; Vaccine; Immunotherapy; Ipilimumab; cytotoxic T-lymphocyte-associated protein 4 (CTLA-4); antibody; FOLFIRINOX
• Additional relevant MeSH terms: Pancreatic Neoplasms; Ipilimumab; Folfirinox; Vaccines

Study Results

Participant Flow

Arm/Group Title	Ipilimumab + Vaccine	FOLFIRINOX
Arm/Group Description	Ipilimumab and vaccine will be administered every 3 weeks for 4 doses, then every 8 weeks. Ipilimumab: 3 mg/kg administered IV (10mg/kg if treatment started prior to protocol v 6.3) Vaccine: 5x10^8 cells administered in 6 intradermal injections	Administered every 14 days (one cycle) FOLFIRINOX: Standard of care FOLFIRINOX may be modified according to the patient's known tolerability. Acceptable modified options could include 5-FU alone, capecitabine, FOLFOX, FOLFIRI, or FOLFIRINOX on a 21 day cycle.
Period Title: Overall Study
STARTED	41	42
COMPLETED	40	36
NOT COMPLETED	1	6

Baseline Characteristics

Arm/Group Title	Ipilimumab + Vaccine	FOLFIRINOX	Total
Arm/Group Description	Ipilimumab and vaccine will be administered every 3 weeks for 4 doses, then every 8 weeks. Ipilimumab: 3 mg/kg administered IV (10mg/kg if treatment started prior to protocol v 6.3) Vaccine: 5x10^8 cells administered in 6 intradermal injections	Administered every 14 days (one cycle) FOLFIRINOX: Standard of care FOLFIRINOX may be modified according to the patient's known tolerability. Acceptable modified options could include 5-FU alone, capecitabine, FOLFOX, FOLFIRI, or FOLFIRINOX on a 21 day cycle.	Total of all reporting groups
Overall Participants	41	42	83
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	30 73.2%	26 61.9%	56 67.5%
>=65 years	11 26.8%	16 38.1%	27 32.5%
Sex: Female, Male (Count of Participants)
Female	17 41.5%	16 38.1%	33 39.8%
Male	24 58.5%	26 61.9%	50 60.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	3 7.1%	3 3.6%
Not Hispanic or Latino	41 100%	39 92.9%	80 96.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	4 9.8%	3 7.1%	7 8.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 2.4%	3 7.1%	4 4.8%
White	36 87.8%	36 85.7%	72 86.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
CA19-9 Secretors (Count of Participants)
Count of Participants [Participants]	32 78%	31 73.8%	63 75.9%
CA19-9 at baseline (IU/mL) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [IU/mL]	185.0	85.0	117.1

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
Description	Overall Survival is the time between the date of randomization on study and death.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

1 Arm A (Ipilimumab + Vaccine) patient was lost to follow-up prior to treatment and was excluded from analysis.

Arm/Group Title	Ipilimumab + Vaccine	FOLFIRINOX
Arm/Group Description	Ipilimumab and vaccine will be administered every 3 weeks for 4 doses, then every 8 weeks. Ipilimumab: 3 mg/kg administered IV (10mg/kg if treatment started prior to protocol v 6.3) Vaccine: 5x10^8 cells administered in 6 intradermal injections	Administered every 14 days (one cycle) FOLFIRINOX: Standard of care FOLFIRINOX may be modified according to the patient's known tolerability. Acceptable modified options could include 5-FU alone, capecitabine, FOLFOX, FOLFIRI, or FOLFIRINOX on a 21 day cycle.
Measure Participants	40	42
Median (95% Confidence Interval) [Months]	9.38	14.7

2. Secondary Outcome

Title	Toxicity of Ipilimumab in Combination With Pancreatic Tumor Vaccine
Description	Toxicity was assessed as the number of patients experiencing study drug-related adverse events (AEs). Data reported for only study drug-related adverse events (not all adverse events as reported in the adverse events section).
Time Frame	From the first dose of study drug through 70 days after last dose, up to 13 months

Outcome Measure Data

Analysis Population Description

AEs were not collected for Arm B subjects (FOLFIRINOX). 39 Arm A subjects (Ipilimumab+Vaccine) received at least 1 dose of study drug and were evaluable for toxicity. Dose of Ipilimumab was reduced from 10 mg/kg to 3 mg/kg due to toxicity concerns. Toxicity rates are compared between these dosing subgroups.

Arm/Group Title	3 mg/kg	10 mg/kg
Arm/Group Description	Ipilimumab and vaccine administered every 3 weeks for 4 doses, then every 8 weeks. Ipilimumab: 3 mg/kg administered IV Vaccine: 5x10^8 cells administered in 6 intradermal injections	Ipilimumab and vaccine administered every 3 weeks for 4 doses, then every 8 weeks. Ipilimumab: 10 mg/kg administered IV Vaccine: 5x10^8 cells administered in 6 intradermal injections
Measure Participants	14	25
Any study drug-related AE	13 31.7%	25 59.5%
adrenal insufficiency	0 0%	1 2.4%
alopecia	0 0%	1 2.4%
ALT increased	0 0%	2 4.8%
arthralgia	0 0%	2 4.8%
AST increased	0 0%	1 2.4%
chills	2 4.9%	5 11.9%
colitis	1 2.4%	4 9.5%
cough	0 0%	1 2.4%
diarrhea	1 2.4%	2 4.8%
dry mouth	0 0%	1 2.4%
dry skin	1 2.4%	0 0%
edema face	0 0%	1 2.4%
fatigue	1 2.4%	7 16.7%
fever	3 7.3%	11 26.2%
flu-like symptoms	1 2.4%	2 4.8%
flushing	0 0%	1 2.4%
hepatitis	0 0%	1 2.4%
hyperhidrosis	0 0%	2 4.8%
hypophysitis	1 2.4%	2 4.8%
hypotension	0 0%	1 2.4%
hypothyroidism	0 0%	1 2.4%
lymph node pain	0 0%	2 4.8%
lymph node swelling	0 0%	1 2.4%
malaise	1 2.4%	0 0%
myalgia	2 4.9%	0 0%
nausea	1 2.4%	2 4.8%
pneumonitis	0 0%	1 2.4%
pruritus	2 4.9%	7 16.7%
rash	8 19.5%	18 42.9%
swelling, chest wall mass	0 0%	1 2.4%
thyroiditis	0 0%	1 2.4%
urticaria	2 4.9%	1 2.4%
vomiting	1 2.4%	2 4.8%
weight loss	0 0%	1 2.4%
vaccine site blisters	1 2.4%	4 9.5%
vaccine site bruising	1 2.4%	2 4.8%
vaccine site erythema	11 26.8%	20 47.6%
vaccine site flares	0 0%	2 4.8%
vaccine site induration	12 29.3%	25 59.5%
vaccine site oozing	0 0%	1 2.4%
vaccine site pruritus	11 26.8%	22 52.4%
vaccine site scabbing	0 0%	1 2.4%
vaccine site tenderness	3 7.3%	13 31%

3. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	Progression Free Survival is the time from date of randomization to progression or death, whichever comes first. Individuals without follow-up scans were censored one day after randomization and individuals with follow-up scans who did not have disease progression were censored at date of last scan.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

1 Arm A patient was lost to follow-up prior to treatment and was excluded from analysis.

Arm/Group Title	Ipilimumab + Vaccine	FOLFIRINOX
Arm/Group Description	Ipilimumab and vaccine will be administered every 3 weeks for 4 doses, then every 8 weeks. Ipilimumab: 3 mg/kg administered IV (10mg/kg if treatment started prior to protocol v 6.3) Vaccine: 5x10^8 cells administered in 6 intradermal injections	Administered every 14 days (one cycle) FOLFIRINOX: Standard of care FOLFIRINOX may be modified according to the patient's known tolerability. Acceptable modified options could include 5-FU alone, capecitabine, FOLFOX, FOLFIRI, or FOLFIRINOX on a 21 day cycle.
Measure Participants	40	42
Median (95% Confidence Interval) [Months]	2.40	5.55

4. Secondary Outcome

Title	Immune-related Progression Free Survival (irPFS)
Description	Immune-related Progression Free Survival is the median time from date of randomization to disease progression or death, whichever comes first. Individuals without follow-up scans were censored one day after randomization and individuals with follow-up scans who did not have disease progression were censored at date of last scan. Disease progression was evaluated using immune-related Response Criteria (irRC). irRC differs from RECIST primarily in that target lesions are measured in 2 dimensions and new lesions contribute to tumor burden, but do not by themselves qualify as progressive disease.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

1 Arm A patient was lost to follow-up prior to treatment and was excluded from analysis.

Arm/Group Title	Ipilimumab + Vaccine	FOLFIRINOX
Arm/Group Description	Ipilimumab and vaccine will be administered every 3 weeks for 4 doses, then every 8 weeks. Ipilimumab: 3 mg/kg administered IV (10mg/kg if treatment started prior to protocol v 6.3) Vaccine: 5x10^8 cells administered in 6 intradermal injections	Administered every 14 days (one cycle) FOLFIRINOX: Standard of care FOLFIRINOX may be modified according to the patient's known tolerability. Acceptable modified options could include 5-FU alone, capecitabine, FOLFOX, FOLFIRI, or FOLFIRINOX on a 21 day cycle.
Measure Participants	40	42
Median (95% Confidence Interval) [Months]	2.50	5.55

5. Secondary Outcome

Title	Objective Response Rate
Description	Objective Response Rate (ORR) is defined as the number of patients from each group achieving a Complete Response (CR) or Partial Response (PR) by Response Evaluation Criteria In Solid Tumors (RECIST).
Time Frame	Assessed until disease progression, up to 2 years

Outcome Measure Data

Analysis Population Description

6 Arm A patients were excluded from analysis (1 lost to follow-up prior to treatment, 1 off study before first follow-up scan, 4 had no measurable disease at baseline and therefore could not have a radiographic response). 13 Arm B patients were excluded from analysis (7 came off study before first follow-up scan, 6 had no measurable disease)

Arm/Group Title	Ipilimumab + Vaccine	FOLFIRINOX
Arm/Group Description	Ipilimumab and vaccine will be administered every 3 weeks for 4 doses, then every 8 weeks. Ipilimumab: 3 mg/kg administered IV (10mg/kg if treatment started prior to protocol v 6.3) Vaccine: 5x10^8 cells administered in 6 intradermal injections	Administered every 14 days (one cycle) FOLFIRINOX: Standard of care FOLFIRINOX may be modified according to the patient's known tolerability. Acceptable modified options could include 5-FU alone, capecitabine, FOLFOX, FOLFIRI, or FOLFIRINOX on a 21 day cycle.
Measure Participants	35	29
Count of Participants [Participants]	1 2.4%	3 7.1%

6. Secondary Outcome

Title	Immune-related Objective Response Rate
Description	Immune-related Objective Response Rate (irORR) is measured the same way, except that tumor responses are evaluated using immune-related response criteria (irRC). irRC differs from RECIST primarily in that target lesions are measured in 2 dimensions and new lesions contribute to tumor burden, but do not by themselves qualify as progressive disease.
Time Frame	Assessed until disease progression, up to 2 years

Outcome Measure Data

Analysis Population Description

6 Arm A patients were excluded from analysis (1 lost to follow-up prior to treatment, 1 off study before first follow-up scan, 4 had no measurable disease at baseline and therefore could not have a radiographic response). 13 Arm B patients were excluded from analysis (7 came off study before first follow-up scan, 6 had no measurable disease)

Arm/Group Title	Ipilimumab + Vaccine	FOLFIRINOX
Arm/Group Description	Ipilimumab and vaccine will be administered every 3 weeks for 4 doses, then every 8 weeks. Ipilimumab: 3 mg/kg administered IV (10mg/kg if treatment started prior to protocol v 6.3) Vaccine: 5x10^8 cells administered in 6 intradermal injections	Administered every 14 days (one cycle) FOLFIRINOX: Standard of care FOLFIRINOX may be modified according to the patient's known tolerability. Acceptable modified options could include 5-FU alone, capecitabine, FOLFOX, FOLFIRI, or FOLFIRINOX on a 21 day cycle.
Measure Participants	35	29
Count of Participants [Participants]	2 4.9%	4 9.5%

7. Secondary Outcome

Title	Duration of Response
Description	Average length of time between achieving a complete response (CR) or partial response (PR) and documentation of recurrent or progressive disease.
Time Frame	Up to 22 months

Outcome Measure Data

Analysis Population Description

Only 1 patient on Arm A (Ipilimumab + Vaccine) and 3 patients on Arm B (FOLFIRINOX) achieved a response by RECIST and were included in this analysis. 2 additional patients (1 Arm A and 1 Arm B) achieved a response by irRC, but these patients were both taken off study the same day as their partial response, for disease progression by RECIST.

Arm/Group Title	Ipilimumab + Vaccine	FOLFIRINOX
Arm/Group Description	Ipilimumab and vaccine will be administered every 3 weeks for 4 doses, then every 8 weeks. Ipilimumab: 3 mg/kg administered IV (10mg/kg if treatment started prior to protocol v 6.3) Vaccine: 5x10^8 cells administered in 6 intradermal injections	Administered every 14 days (one cycle) FOLFIRINOX: Standard of care FOLFIRINOX may be modified according to the patient's known tolerability. Acceptable modified options could include 5-FU alone, capecitabine, FOLFOX, FOLFIRI, or FOLFIRINOX on a 21 day cycle.
Measure Participants	1	3
Mean (Full Range) [months]	2.5	8.49

8. Secondary Outcome

Title	Tumor Marker Kinetics as Assessed by Median Carbohydrate Antigen 19-9 (CA19-9) Levels
Description	Carbohydrate Antigen 19-9 (CA19-9) is a tumor marker measured in the blood of patients with pancreas cancer. Not all patients with pancreas cancer will have elevated CA19-9 and there are some conditions other than cancer that can cause an elevated CA19-9. Normal CA19-9 range is 0-36 U/mL.
Time Frame	Baseline, Week 7, and Week 10 visits

Outcome Measure Data

Analysis Population Description

Only patients who were considered CA19-9 secretors (expressed CA19-9 either on study or prior to study) were included in the analysis. 32 in Arm A (Ipilimumab+Vaccine) and 31 in Arm B (FOLFIRINOX). Only subjects evaluable for this outcome at the specified time points had CA19-9 drawn and could be included in the analysis.

Arm/Group Title	Ipilimumab + Vaccine	FOLFIRINOX
Arm/Group Description	Ipilimumab and vaccine administered every 3 weeks for 4 doses, then every 8 weeks. Ipilimumab: 3 mg/kg administered IV (10mg/kg if treatment started prior to protocol v 6.3) Vaccine: 5x10^8 cells administered in 6 intradermal injections	Administered every 14 days (one cycle) FOLFIRINOX: Standard of care FOLFIRINOX may be modified according to the patient's known tolerability. Acceptable modified options could include 5-FU alone, capecitabine, FOLFOX, FOLFIRI, or FOLFIRINOX on a 21 day cycle.
Measure Participants	32	31
Baseline	185.0	85.0
Week 7	189.2	77.9
Week 10	237.1	66.8

Adverse Events

Time Frame	Adverse Events were collected from the first dose of study drug through 70 days after the last dose of study drug, up to 13 months
Adverse Event Reporting Description	AEs were not collected for Arm B subjects (FOLFIRINOX). 39 Arm A subjects (Ipilimumab+Vaccine) received at least 1 dose of study drug and were evaluable for toxicity.
Arm/Group Title	Ipilimumab + Vaccine
Arm/Group Description	Ipilimumab and vaccine administered every 3 weeks for 4 doses, then every 8 weeks. Ipilimumab: 3 mg/kg administered IV (10mg/kg if treatment started prior to protocol v 6.3) Vaccine: 5x10^8 cells administered in 6 intradermal injections
All Cause Mortality
	Ipilimumab + Vaccine
	Affected / at Risk (%)	# Events
Total	5/39 (12.8%)
Serious Adverse Events
	Ipilimumab + Vaccine
	Affected / at Risk (%)	# Events
Total	20/39 (51.3%)
Endocrine disorders
adrenal insufficiency	1/39 (2.6%)
hypophysitis	1/39 (2.6%)
Gastrointestinal disorders
abdominal pain	2/39 (5.1%)
colitis	3/39 (7.7%)
diarrhea	2/39 (5.1%)
malabsorption	1/39 (2.6%)
nausea	1/39 (2.6%)
obstruction gastric	1/39 (2.6%)
vomiting	2/39 (5.1%)
Infections and infestations
bacteremia	1/39 (2.6%)
catheter related infection	1/39 (2.6%)
lung infection	2/39 (5.1%)
sepsis	2/39 (5.1%)
Investigations
alkaline phosphatase increased	1/39 (2.6%)
blood bilirubin increased	2/39 (5.1%)
INR increased	1/39 (2.6%)
neutropenia	1/39 (2.6%)
platelet count decreased	1/39 (2.6%)
weight loss	1/39 (2.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
death, disease progression	5/39 (12.8%)
Psychiatric disorders
delerium	1/39 (2.6%)
Renal and urinary disorders
acute kidney injury	1/39 (2.6%)
Respiratory, thoracic and mediastinal disorders
chest wall pain	1/39 (2.6%)
dyspnea	1/39 (2.6%)
pneumonitis	1/39 (2.6%)
Vascular disorders
thromboembolic event - pulmonary embolism	1/39 (2.6%)
Other (Not Including Serious) Adverse Events
	Ipilimumab + Vaccine
	Affected / at Risk (%)	# Events
Total	39/39 (100%)
Blood and lymphatic system disorders
lymph node pain	2/39 (5.1%)
Cardiac disorders
sinus tachycardia	4/39 (10.3%)
Endocrine disorders
hypophysitis	3/39 (7.7%)
Gastrointestinal disorders
abdominal distention	3/39 (7.7%)
abdominal pain	13/39 (33.3%)
ascites	5/39 (12.8%)
bloating	5/39 (12.8%)
colitis	4/39 (10.3%)
constipation	14/39 (35.9%)
diarrhea	12/39 (30.8%)
dry mouth	3/39 (7.7%)
dyspepsia	3/39 (7.7%)
flatulence	2/39 (5.1%)
nausea	12/39 (30.8%)
oral pain	2/39 (5.1%)
vomiting	11/39 (28.2%)
General disorders
chills	12/39 (30.8%)
cold intolerance	2/39 (5.1%)
edema limbs	5/39 (12.8%)
fatigue	17/39 (43.6%)
fever	20/39 (51.3%)
flu-like symptoms	3/39 (7.7%)
gait disturbance	2/39 (5.1%)
non-cardiac pain	5/39 (12.8%)
vaccine site blisters	5/39 (12.8%)
vaccine site bruising	3/39 (7.7%)
vaccine site erythema	31/39 (79.5%)
vaccine site flares	2/39 (5.1%)
vaccine site induration	37/39 (94.9%)
vaccine site pruritus	33/39 (84.6%)
vaccine site tenderness	16/39 (41%)
Infections and infestations
upper respiratory infection	3/39 (7.7%)
urinary tract infection	2/39 (5.1%)
Injury, poisoning and procedural complications
bruising	4/39 (10.3%)
fall	2/39 (5.1%)
pain, site of procedure/conmed	3/39 (7.7%)
Investigations
alkaline phosphatase increased	3/39 (7.7%)
alanine aminotransferase (ALT) increased	5/39 (12.8%)
anemia	4/39 (10.3%)
aspartate aminotransferase (AST) increased	3/39 (7.7%)
blood bilirubin increased	2/39 (5.1%)
lymphocyte count decreased	2/39 (5.1%)
platelet count decreased	4/39 (10.3%)
weight loss	5/39 (12.8%)
Metabolism and nutrition disorders
anorexia	9/39 (23.1%)
hyperglycemia	2/39 (5.1%)
hypokalemia	2/39 (5.1%)
hypophosphatemia	2/39 (5.1%)
Musculoskeletal and connective tissue disorders
arthralgia	6/39 (15.4%)
back pain	7/39 (17.9%)
muscle cramp	3/39 (7.7%)
myalgia	2/39 (5.1%)
Nervous system disorders
dizziness	4/39 (10.3%)
headache	6/39 (15.4%)
peripheral sensory neuropathy	2/39 (5.1%)
Psychiatric disorders
anxiety	7/39 (17.9%)
depression	3/39 (7.7%)
insomnia	12/39 (30.8%)
Renal and urinary disorders
difficulty urinating	2/39 (5.1%)
urinary frequency	2/39 (5.1%)
Reproductive system and breast disorders
rhinitis	2/39 (5.1%)
Respiratory, thoracic and mediastinal disorders
atelectasis	4/39 (10.3%)
cough	6/39 (15.4%)
dyspnea	5/39 (12.8%)
pleural effusion	3/39 (7.7%)
Skin and subcutaneous tissue disorders
dry skin	2/39 (5.1%)
hyperhidrosis	5/39 (12.8%)
pruritus	9/39 (23.1%)
rash	28/39 (71.8%)
urticaria	3/39 (7.7%)
Vascular disorders
hot flashes	2/39 (5.1%)
hypotension	5/39 (12.8%)
thromboembolic event	3/39 (7.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Principal Investigators (PIs) from participating sites must provide the Johns Hopkins PI with a copy of any proposed publication for review and comment at least 30 days prior to submission.