GVAX Pancreas Vaccine (With CY) and CRS-207 With or Without Nivolumab

• ClinicalTrials.gov Identifier: NCT02243371
• Recruitment Status: Completed
• First Posted: September 17, 2014
• Results First Posted: October 8, 2019
• Last Update Posted: April 6, 2021
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Bristol-Myers Squibb; Stand Up To Cancer; Aduro Biotech, Inc.; American Association for Cancer Research; Lustgarten Foundation
• Information provided by (Responsible Party): Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Previously Treated Metastatic Adenocarcinoma of the Pancreas
• Interventions: Biological: CRS-207; Drug: nivolumab; Biological: GVAX; Drug: CY
• Enrollment: 93

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	CY/ GVAX/ CRS-207/ Nivolumab	CY/ GVAX/ CRS-207
Arm/Group Description	CRS-207: 1 × 10^9 CFU administered IV on Day 2 of Cycles 3-6 GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2 nivolumab: 3 mg/kg administered IV on Day 1 of Cycles 1-6 CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2	CRS-207: 1 × 10^9 CFU administered IV Day 1 of Cycles 3-6 GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2 CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2
Period Title: Overall Study
Started	51	42
Completed	14	10
Not Completed	37	32
Reason Not Completed
Progressive Disease (clinic & radio)	35	24
Death (unrelated)	2	4
Adverse Event (unrelated)	0	1
Lack of Clinical Benefit	0	1
Withdrawal by Subject	0	2

Baseline Characteristics

Arm/Group Title		CY/ GVAX/ CRS-207/ Nivolumab	CY/ GVAX/ CRS-207	Total
Arm/Group Description		CRS-207: 1 × 10^9 CFU administered IV on Day 2 of Cycles 3-6 GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2 nivolumab: 3 mg/kg administered IV on Day 1 of Cycles 1-6 CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2	CRS-207: 1 × 10^9 CFU administered IV Day 1 of Cycles 3-6 GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2 CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2	Total of all reporting groups
Overall Number of Baseline Participants		51	42	93
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	51 participants	42 participants	93 participants
		63.6 (8.08)	63.2 (9.28)	63.4 (8.60)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	51 participants	42 participants	93 participants
	Female	14 27.5%	18 42.9%	32 34.4%
	Male	37 72.5%	24 57.1%	61 65.6%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	51 participants	42 participants	93 participants
	Hispanic or Latino	2 3.9%	0 0.0%	2 2.2%
	Not Hispanic or Latino	46 90.2%	38 90.5%	84 90.3%
	Unknown or Not Reported	3 5.9%	4 9.5%	7 7.5%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	51 participants	42 participants	93 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	5 9.8%	5 11.9%	10 10.8%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	4 9.5%	4 4.3%
	White	44 86.3%	33 78.6%	77 82.8%
	More than one race	2 3.9%	0 0.0%	2 2.2%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
Description	OS will be measured from date of randomization until death or end of followup (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis).
Time Frame	2 years and 7 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A: CY/ GVAX/ CRS-207/ Nivolumab	Arm B: CY/ GVAX/ CRS-207
Arm/Group Description:	CRS-207: 1 × 10^9 CFU administered IV on Day 2 of Cycles 3-6 GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2 nivolumab: 3 mg/kg administered IV on Day 1 of Cycles 1-6 CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2	CRS-207: 1 × 10^9 CFU administered IV on Day 1 of Cycles 3-6 GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2 CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2
Overall Number of Participants Analyzed	51	42
Median (95% Confidence Interval); Unit of Measure: months
	5.88; (4.73 to 8.64)	6.11; (3.52 to 7.00)

2. Secondary Outcome

Title	Number of Patients Experiencing a Grade 3 or Above Treatment-related Toxicity
Description	When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v4.03) will be counted only once for a given subject.
Time Frame	2 years and 7 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A: CY/ GVAX/ CRS-207/ Nivolumab	Arm B: CY/ GVAX/ CRS-207
Arm/Group Description:	CRS-207: 1 × 10^9 CFU administered IV on Day 2 of Cycles 3-6 GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2 nivolumab: 3 mg/kg administered IV on Day 1 of Cycles 1-6 CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2	CRS-207: 1 × 10^9 CFU administered IV on Day 1 of Cycles 3-6 GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2 CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2
Overall Number of Participants Analyzed	51	42
Measure Type: Count of Participants; Unit of Measure: Participants
	18 35.3%	5 11.9%

3. Secondary Outcome

Title	Progression-free Survival (PFS) in Metastatic Pancreatic Cancer Patients
Description	PFS is defined as the number of months from the date of randomization to disease progression (progressive disease [PD] or relapse from complete response [CR] as assessed using RECIST 1.1 criteria) or death due to any cause. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.
Time Frame	2 years and 7 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A: CY/ GVAX/ CRS-207/ Nivolumab	Arm B: CY/ GVAX/ CRS-207
Arm/Group Description:	CRS-207: 1 × 10^9 CFU administered IV on Day 2 of Cycles 3-6 GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2 nivolumab: 3 mg/kg administered IV on Day 1 of Cycles 1-6 CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2	CRS-207: 1 × 10^9 CFU administered IV on Day 1 of Cycles 3-6 GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2 CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2
Overall Number of Participants Analyzed	51	42
Median (95% Confidence Interval); Unit of Measure: months
	2.23; (2.14 to 2.33)	2.17; (2.00 to 2.30)

4. Secondary Outcome

Title	Immune-related Progression-free Survival (irPFS) by IRRC in Metastatic Pancreatic Cancer Patients
Description	irPFS is defined as the number of months from the date of randomization to disease progression (PD or relapse from CR as assessed using irRC RECIST 1.1 criteria) or death due to any cause. Per irRC criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in tumor burden compared with baseline, Progressive Disease (PD) is >20% increase in tumor burden compared with nadir, Stable Disease (SD) is <30% decrease in tumor burden compared with baseline or <20% increase in tumor burden compared to nadir.
Time Frame	2 years and 7 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A: CY/ GVAX/ CRS-207/ Nivolumab	Arm B: CY/ GVAX/ CRS-207
Arm/Group Description:	CRS-207: 1 × 10^9 CFU administered IV on Day 2 of Cycles 3-6 GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2 nivolumab: 3 mg/kg administered IV on Day 1 of Cycles 1-6 CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2	CRS-207: 1 × 10^9 CFU administered IV on Day 1 of Cycles 3-6 GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2 CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2
Overall Number of Participants Analyzed	51	42
Mean (95% Confidence Interval); Unit of Measure: months
	2.27; (2.17 to 2.33)	2.23; (2.10 to 2.40)

5. Secondary Outcome

Title	Time to Progression (TTP) by RECIST 1.1 in Metastatic Pancreatic Cancer Patients
Description	Time to progression (TTP) is defined as the time from randomization to the date of documented disease progression as defined by RECIST 1.1 criteria. Individuals are censored at the date of the last radiological assessment that occurs prior to any of the following: death, switch to another anti-cancer therapy, or end of follow-up. Individuals without follow-up or baseline measurements are censored at 1 day. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.
Time Frame	2 years and 7 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A: CY/ GVAX/ CRS-207/ Nivolumab	Arm B: CY/ GVAX/ CRS-207
Arm/Group Description:	CRS-207: 1 × 10^9 CFU administered IV on Day 2 of Cycles 3-6 GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2 nivolumab: 3 mg/kg administered IV on Day 1 of Cycles 1-6 CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2	CRS-207: 1 × 10^9 CFU administered IV on Day 1 of Cycles 3-6 GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2 CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2
Overall Number of Participants Analyzed	51	42
Median (95% Confidence Interval); Unit of Measure: months
	2.20; (2.10 to 2.33)	2.20; (2.00 to 2.30)

6. Secondary Outcome

Title	Number of Participants With Partial Response (PR) or Complete Response (CR) as Defined by RECIST 1.1 in Metastatic Pancreatic Cancer Patients
Description	Per RECIST 1.1 criteria, PR is defined as =>30% decrease in sum of diameters of target lesions and CR is the disappearance of all target lesions.
Time Frame	2 years and 7 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A: CY/ GVAX/ CRS-207/ Nivolumab	Arm B: CY/ GVAX/ CRS-207
Arm/Group Description:	CRS-207: 1 × 10^9 CFU administered IV on Day 2 of Cycles 3-6 GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2 nivolumab: 3 mg/kg administered IV on Day 1 of Cycles 1-6 CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2	CRS-207: 1 × 10^9 CFU administered IV on Day 1 of Cycles 3-6 GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2 CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2
Overall Number of Participants Analyzed	51	42
Measure Type: Count of Participants; Unit of Measure: Participants
	1 2.0%	1 2.4%

7. Secondary Outcome

Title	Tumor Marker Kinetics (CA 19-9) in Patients With Baseline Abnormal Levels as Measured by Number of Participants With Stable or Responding CA19-9 Concentration
Description	Number of participants with stable or responding (<50% increase of serum CA19-9 concentration) at 120 days.
Time Frame	120 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A: CY/ GVAX/ CRS-207/ Nivolumab	Arm B: CY/ GVAX/ CRS-207
Arm/Group Description:	CRS-207: 1 × 10^9 CFU administered IV on Day 2 of Cycles 3-6 GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2 nivolumab: 3 mg/kg administered IV on Day 1 of Cycles 1-6 CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2	CRS-207: 1 × 10^9 CFU administered IV on Day 1 of Cycles 3-6 GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2 CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2
Overall Number of Participants Analyzed	51	42
Measure Type: Count of Participants; Unit of Measure: Participants
	18 35.3%	7 16.7%

Adverse Events

Time Frame	2 years and 7 months
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Arm A: CY/ GVAX/ CRS-207/ Nivolumab		Arm B: CY/ GVAX/ CRS-207
Arm/Group Description	CRS-207: 1 × 10^9 CFU administered IV on Day 2 of Cycles 3-6 GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2 nivolumab: 3 mg/kg administered IV on Day 1 of Cycles 1-6 CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2		CRS-207: 1 × 10^9 CFU administered IV on Day 1 of Cycles 3-6 GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2 CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2
All-Cause Mortality
	Arm A: CY/ GVAX/ CRS-207/ Nivolumab		Arm B: CY/ GVAX/ CRS-207
	Affected / at Risk (%)		Affected / at Risk (%)
Total	45/51 (88.24%)		36/42 (85.71%)
Serious Adverse Events
	Arm A: CY/ GVAX/ CRS-207/ Nivolumab		Arm B: CY/ GVAX/ CRS-207
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/51 (9.80%)		1/42 (2.38%)
Blood and lymphatic system disorders
THROMBOCYTOPENIA †	1/51 (1.96%)	1	0/42 (0.00%)	0
Cardiac disorders
MYOCARDITIS †	1/51 (1.96%)	1	0/42 (0.00%)	0
Gastrointestinal disorders
DIARRHOEA †	1/51 (1.96%)	1	0/42 (0.00%)	0
Infections and infestations
LISTERIA SEPSIS †	0/51 (0.00%)	0	1/42 (2.38%)	1
Metabolism and nutrition disorders
Dehydration †	1/51 (1.96%)	1	0/42 (0.00%)	0
HYPERGLYCAEMIA †	1/51 (1.96%)	1	0/42 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
PNEUMONITIS †	1/51 (1.96%)	1	0/42 (0.00%)	0
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Arm A: CY/ GVAX/ CRS-207/ Nivolumab		Arm B: CY/ GVAX/ CRS-207
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	46/51 (90.20%)		40/42 (95.24%)
Blood and lymphatic system disorders
LYMPHOPENIA †	4/51 (7.84%)		1/42 (2.38%)
Cardiac disorders
SINUS TACHYCARDIA †	7/51 (13.73%)		6/42 (14.29%)
TACHYCARDIA †	5/51 (9.80%)		2/42 (4.76%)
Gastrointestinal disorders
NAUSEA †	17/51 (33.33%)		19/42 (45.24%)
VOMITING †	4/51 (7.84%)		5/42 (11.90%)
General disorders
VACCINATION SITE ERYTHEMA †	46/51 (90.20%)		40/42 (95.24%)
VACCINATION SITE INDURATION †	41/51 (80.39%)		31/42 (73.81%)
CHILLS †	42/51 (82.35%)		29/42 (69.05%)
VACCINATION SITE PRURITUS †	36/51 (70.59%)		30/42 (71.43%)
PYREXIA †	38/51 (74.51%)		27/42 (64.29%)
VACCINATION SITE PAIN †	34/51 (66.67%)		29/42 (69.05%)
VACCINATION SITE DISCOMFORT †	22/51 (43.14%)		21/42 (50.00%)
FATIGUE †	23/51 (45.10%)		12/42 (28.57%)
INFLUENZA LIKE ILLNESS †	13/51 (25.49%)		8/42 (19.05%)
VACCINATION SITE OEDEMA †	9/51 (17.65%)		8/42 (19.05%)
VACCINATION SITE SWELLING †	3/51 (5.88%)		5/42 (11.90%)
VACCINATION SITE VESICLES †	5/51 (9.80%)		3/42 (7.14%)
VACCINATION SITE REACTION †	5/51 (9.80%)		2/42 (4.76%)
VACCINATION SITE BRUISING †	4/51 (7.84%)		2/42 (4.76%)
PAIN †	2/51 (3.92%)		3/42 (7.14%)
Investigations
ALANINE AMINOTRANSFERASE INCREASED †	6/51 (11.76%)		0/42 (0.00%)
ASPARTATE AMINOTRANSFERASE INCREASED †	4/51 (7.84%)		1/42 (2.38%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA †	7/51 (13.73%)		4/42 (9.52%)
MYALGIA †	7/51 (13.73%)		2/42 (4.76%)
Nervous system disorders
HEADACHE †	10/51 (19.61%)		6/42 (14.29%)
DIZZINESS †	4/51 (7.84%)		3/42 (7.14%)
Vascular disorders
HYPERTENSION †	6/51 (11.76%)		4/42 (9.52%)
HYPOTENSION †	6/51 (11.76%)		1/42 (2.38%)
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Dung Le, MD
• Organization: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Phone: 443-287-0002
• EMail: dle@jhmi.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Hopkins AC, Yarchoan M, Durham JN, Yusko EC, Rytlewski JA, Robins HS, Laheru DA, Le DT, Lutz ER, Jaffee EM. T cell receptor repertoire features associated with survival in immunotherapy-treated pancreatic ductal adenocarcinoma. JCI Insight. 2018 Jul 12;3(13):e122092. doi: 10.1172/jci.insight.122092.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT02243371
• Other Study ID Numbers: J14113; ADU-CL-06; IRB00043936 ( Other Identifier: JHMIRB )
• First Submitted: September 15, 2014
• First Posted: September 17, 2014
• Results First Submitted: August 6, 2019
• Results First Posted: October 8, 2019
• Last Update Posted: April 6, 2021