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

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

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).

Study Overview

• Status: Completed
• Conditions: Previously Treated Metastatic Adenocarcinoma of the Pancreas
• Intervention / Treatment: Biological: CRS-207; Biological: CRS-207; Drug: nivolumab; Biological: GVAX; Drug: CY

• Study Type: Interventional
• Enrollment (Actual): 93
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
    • Stanford, California, United States, 94305
      • Stanford University
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Sidney kimmel comprehensive cancer center at johns hopkins
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: CY/ GVAX/ CRS-207/ nivolumab	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 Names: 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 Names: 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 Names: Cytoxan, Cyclophosphamide
Experimental: Arm B: CY/ GVAX/ CRS-207	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; Biological: GVAX; 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2; Other Names: 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 Names: Cytoxan, Cyclophosphamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	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).	2 years and 7 months

Secondary Outcome Measures

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

Collaborators and Investigators

• 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

Publications and helpful links

General 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):e122092. doi: 10.1172/jci.insight.122092.

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2015
• Primary Completion (Actual): July 21, 2017
• Study Completion (Actual): July 21, 2017

Study Registration Dates

• First Submitted: September 15, 2014
• First Submitted That Met QC Criteria: September 16, 2014
• First Posted (Estimate): September 17, 2014

Study Record Updates

• Last Update Posted (Actual): April 6, 2021
• Last Update Submitted That Met QC Criteria: March 17, 2021
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Cyclophosphamide; Nivolumab
• Other Study ID Numbers: J14113; ADU-CL-06; IRB00043936 (Other Identifier: JHMIRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No