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

Tracking Information

• First Submitted Date: September 15, 2014
• First Posted Date: September 17, 2014
• Results First Submitted Date: August 6, 2019
• Results First Posted Date: October 8, 2019
• Last Update Posted Date: April 6, 2021
• Actual Study Start Date: January 2, 2015
• Actual Primary Completion Date: July 21, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 16, 2019)

Overall Survival (OS) [ Time Frame: 2 years and 7 months ]

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).

• Original Primary Outcome Measures (submitted: September 16, 2014): Overall survival (OS) in metastatic pancreatic cancer patients treated with cyclophosphamide (CY)/nivolumab/GVAX pancreas vaccine followed by nivolumab/CRS-207 (Arm A) versus patients treated with CY/GVAX pancreas vaccine followed by CRS-207 (Arm B) [ Time Frame: 4 years ]

Current Secondary Outcome Measures (submitted: September 16, 2019)

• Number of Patients Experiencing a Grade 3 or Above Treatment-related Toxicity [ Time Frame: 2 years and 7 months ]
  When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v4.03) will be counted only once for a given subject.
• Progression-free Survival (PFS) in Metastatic Pancreatic Cancer Patients [ Time Frame: 2 years and 7 months ]
  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.
• Immune-related Progression-free Survival (irPFS) by IRRC in Metastatic Pancreatic Cancer Patients [ Time Frame: 2 years and 7 months ]
  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 to Progression (TTP) by RECIST 1.1 in Metastatic Pancreatic Cancer Patients [ Time Frame: 2 years and 7 months ]
  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.
• Number of Participants With Partial Response (PR) or Complete Response (CR) as Defined by RECIST 1.1 in Metastatic Pancreatic Cancer Patients [ Time Frame: 2 years and 7 months ]
  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.
• 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 [ Time Frame: 120 days ]
  Number of participants with stable or responding (<50% increase of serum CA19-9 concentration) at 120 days.

Original Secondary Outcome Measures (submitted: September 16, 2014)

• Number of patients experiencing treatment-related toxicities [ Time Frame: 4 years ]
• Progression-free survival (PFS) by RECIST 1.1 in metastatic pancreatic cancer patients treated with CY/GVAX/CRS-207/nivolumab (Arm A) versus patients treated with CY/GVAX/CRS-207 (Arm B) [ Time Frame: 4 years ]
• Immune-related progression-free survival (irPFS) by IRRC in metastatic pancreatic cancer patients treated with CY/GVAX/CRS-207/nivolumab (Arm A) versus patients treated with CY/GVAX/CRS-207 (Arm B) [ Time Frame: 4 years ]
• Time to progression (TTP) by RECIST 1.1 and IRRC in metastatic pancreatic cancer patients treated with CY/GVAX/CRS-207/nivolumab (Arm A) versus patients treated with CY/GVAX/CRS-207 (Arm B) [ Time Frame: 4 years ]
• Response rate measured by RECIST 1.1 in metastatic pancreatic cancer patients treated with CY/GVAX/CRS-207/nivolumab (Arm A) versus patients treated with CY/GVAX/CRS-207 (Arm B) [ Time Frame: 4 years ]
• Tumor marker kinetics (CA 19-9) in metastatic pancreatic cancer patients treated with CY/GVAX/CRS-207/nivolumab (Arm A) versus patients treated with CY/GVAX/CRS-207 (Arm B) [ Time Frame: 4 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: GVAX Pancreas Vaccine (With CY) and CRS-207 With or Without Nivolumab
• Official Title: A Randomized Phase 2 Study of the Safety, Efficacy, and Immune Response of GVAX Pancreas Vaccine (With Cyclophosphamide) and CRS-207 With or Without Nivolumab in Patients With Previously Treated Metastatic Pancreatic Adenocarcinoma
• Brief Summary: The primary objective of this study is to compare the overall survival (OS) of subjects with previously treated metastatic pancreatic cancer treated with cyclophosphamide (CY)/nivolumab/GVAX pancreas vaccine followed by nivolumab/CRS-207 (Arm A) to subjects treated with CY/GVAX pancreas vaccine followed by CRS-207 (Arm B).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Previously Treated Metastatic Adenocarcinoma of the Pancreas

Intervention

• Biological: CRS-207
  1 × 10^9 CFU administered IV on Day 2 of Cycles 3-6
• Biological: CRS-207
  1 × 10^9 CFU administered IV on Day 1 of Cycles 3-6
• Drug: nivolumab
  3 mg/kg administered IV on Day 1 of Cycles 1-6
  Other Name: BMS-936558; anti-PD-1 mAb
• Biological: GVAX
  5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2
  Other Name: GVAX pancreas vaccine, Panc 10.05 pcDNA-1/GM-Neo, Panc 6.03 pcDNA-1/GM-Neo
• Drug: CY
  200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2
  Other Name: Cytoxan, Cyclophosphamide

Study Arms

• Experimental: Arm A: CY/ GVAX/ CRS-207/ nivolumab
  Interventions:

  • Biological: CRS-207
  • Drug: nivolumab
  • Biological: GVAX
  • Drug: CY
• Experimental: Arm B: CY/ GVAX/ CRS-207
  Interventions:

  • Biological: CRS-207
  • Biological: GVAX
  • Drug: CY

• Publications *: 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). pii: 122092. doi: 10.1172/jci.insight.122092.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 16, 2019): 93
• Original Estimated Enrollment (submitted: September 16, 2014): 94
• Actual Study Completion Date: July 21, 2017
• Actual Primary Completion Date: July 21, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age ≥18 years.
• Have histologically- or cytologically-proven adenocarcinoma of the pancreas. Patients with mixed histology will be excluded.
• Have metastatic disease.
• Have failed only 1 prior chemotherapy regimen for metastatic pancreatic cancer.
• Patients with the presence of at least one measurable lesion.
• Patients acceptance to have a tumor biopsy of an accessible lesion at baseline and on treatment if the lesion can be biopsied with acceptable clinical risk (as judged by the investigator).
• ECOG performance status 0 or 1.
• Life expectancy of greater than 3 months.
• Patients must have adequate organ and marrow function defined by study-specified laboratory tests.
• Must use acceptable form of birth control while on study.
• Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

• known history or evidence of brain metastases.
• Had surgery within the last 28 days
• Have received any non-oncology vaccine therapy used for prevention of infectious diseases including seasonal vaccinations within 28 days of study treatment.
• Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4, GVAX or CRS-207
• Systemic steroids within the last 14 days
• Use more than 3 g/day of acetaminophen.
• Patients on immunosuppressive agents.
• Patients receiving growth factors within the last 14 days
• Known allergy to both penicillin and sulfa.
• Severe hypersensitivity reaction to any monoclonal antibody.
• Have artificial joints or implants that cannot be easily removed
• Have any evidence of hepatic cirrhosis or clinical or radiographic ascites.
• Have significant and/or malignant pleural effusion
• Infection with HIV or hepatitis B or C at screening
• Significant heart disease
• Conditions, including alcohol or drug dependence, intercurrent illness, or lack of sufficient peripheral venous access, that would affect the patient's ability to comply with study visits and procedures
• Unable to avoid intimate contact with another individual known to be at high risk of listeriosis (e.g., newborn infant, pregnant woman, HIV-positive individual) during the course of CRS-207 treatment until completion of antibiotic regimen.
• Are pregnant or breastfeeding.
• Have rapidly progressing disease

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02243371
• Other Study ID Numbers: J14113; ADU-CL-06; IRB00043936 ( Other Identifier: JHMIRB )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Study 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

Investigators

• Principal Investigator: Dung Le, MD; Johns Hopkins University

• PRS Account: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Verification Date: February 2020