Platform Study Of Neoadjuvant And Adjuvant Immunotherapy For Patients With Resectable Adenocarcinoma Of The Pancreas

Study Overview

Platform Study of Neoadjuvant and Adjuvant Immunotherapy for Patients With Resectable Adenocarcinoma of the Pancreas

This platform trial will evaluate various immunotherapy combinations given in the neo-adjuvant and adjuvant setting in patients with surgically resectable pancreatic ductal adenocarcinoma.

Immunotherapy is an innovative approach being developed for the treatment of pancreatic cancer, a lethal and relatively chemotherapy-resistant disease. However, the tumor and its environment have developed a number of ways in which they inhibit the function of the immune system preventing it from recognizing and killing the cancer. In addition, the investigators still do not understand how T cells, the cells in the immune system that have the potential to recognize cancer as different and kill cancer cells, traffic into the tumor to accomplish their task. The investigators are currently testing an immune system activating pancreatic cancer vaccine (known as GVAX) in combination with immune boosting doses of the chemotherapy agent, cyclophosphamide, as preoperative and postoperative treatments for pancreatic cancer. The investigators have discovered tertiary lymphoid aggregates, a unique lymph node-like structure formed within resected tumors from the patients who received the vaccine two weeks prior to the surgery. This discovery demonstrates that the immune system can get into the tumor and provides the investigators with the opportunity to better understand how these immune cells traffic into the tumor and function once they arrive. The investigators also found that the vaccine causes an increase in signals that would suppress the immune system's ability to fight off cancer cells, including signals involving PD-1. In this novel study, the investigators will test the effects of blocking PD-1 in combination with the vaccine in patients with pancreatic cancer. The investigators will specifically isolate these immune cells and evaluate at both the genetic and protein level, the types of signals expressed by these aggregates. The investigators will compare aggregates from patients with long term survival versus patients who succumb to their cancer early. In this way, the investigators will be able to determine how safe this novel treatment is, how effective it is at changing the immune system in pancreatic cancer, and how it impacts the health and survival of pancreatic cancer patients who undergo surgery to remove the cancer.

Pancreatic Cancer

DRUG: Cyclophosphamide
BIOLOGICAL: GVAX pancreatic cancer
DRUG: Nivolumab
DRUG: Urelumab
DRUG: BMS-986253

J1568
IRB00050517 (OTHER Identifier) (OTHER: JHMIRB)
R01CA197296 (U.S. NIH Grant/Contract)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2015-05-20	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-04-08
First Submitted that Met QC Criteria 2015-05-20	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-04-11
First Posted (ACTUAL) 2015-05-22	Results First Posted N/A	Last Verified 2025-04

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Arm A: CY/GVAX alone Patients receive low-dose cyclophosphamide IV on day 0 and GVAX pancreatic cancer vaccine ID on day 1. Patients undergo pancreaticoduodenectomy on day 15. Approximately 6-10 weeks after surgery, patients receive low-dose cyclophosphamide IV on day 0 and t	DRUG: Cyclophosphamide 200 mg/m2 IV BIOLOGICAL: GVAX pancreatic cancer 5x10^8 cells intradermal injection
EXPERIMENTAL: Arm B: CY/GVAX with nivolumab Patients receive low-dose cyclophosphamide and nivolumab IV on day 0 and GVAX pancreatic cancer vaccine ID on day 1. Patients undergo pancreaticoduodenectomy on day 15. Approximately 6-10 weeks after surgery, patients receive low-dose cyclophosphamide and	DRUG: Cyclophosphamide 200 mg/m2 IV BIOLOGICAL: GVAX pancreatic cancer 5x10^8 cells intradermal injection DRUG: Nivolumab 480 mg IV
EXPERIMENTAL: Arm C: CY/GVAX with nivolumab and urelumab Patients receive low-dose cyclophosphamide, nivolumab, and urelumab on day 0 and GVAX pancreatic cancer vaccine on day 1. Patients undergo pancreaticoduodenectomy on day 15. Approximately 6-10 weeks after surgery, patients receive low-dose cyclophosphamid	DRUG: Cyclophosphamide 200 mg/m2 IV BIOLOGICAL: GVAX pancreatic cancer 5x10^8 cells intradermal injection DRUG: Nivolumab 480 mg IV DRUG: Urelumab 8 mg IV
EXPERIMENTAL: Arm D: BMS-986253 and Nivolumab Patients receive BMS-986253 and nivolumab on day 0 (Cycle 1), 15 days prior to surgery. 6-10 weeks after surgery, patients receive Cycle 2, with nivolumab on day 0 and BMS-986253 on days 0 and 14. Patients then receive standard adjuvant chemoradiotherapy.	DRUG: Nivolumab 480 mg IV DRUG: BMS-986253 2400 mg IV

Primary Outcome Measures	Measure Description	Time Frame
IL17A expression	median IL17A expression in lymphoid aggregates from resected tumor (Arms A and B only)	4 years
Intratumoral CD8+CD137+cells	Fold change of intratumoral CD8+CD137+cells before and after neoadjuvant therapy (Arms B and C only)	4 years
Intratumoral granzyme B+PD-1+CD137+ cells	Percent change of intratumoral granzyme B+PD-1+CD137+ cells in surgical (post-treatment) tissue compared to baseline (pre-treatment) biopsy (Arm D only)	4 years
Pathologic Response	Percent of patients with a response grade of 0-2 (0=complete response 1=marked response, 2=moderate response) at time of surgery	4 years

Secondary Outcome Measures	Measure Description	Time Frame
Drug-Related Adverse Events	Number of participants experiencing study drug-related toxicities	4 years
Overall Survival	Overall Survival is defined as the time from surgery to death from any cause	4 years
Disease Free Survival	Disease Free Survival is defined as the time from surgery until evidence of disease recurrence or death from any cause	4 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Colleen Apostol, RN

Phone Number: 410-614-3644

Email: GIClinicalTrials@jhmi.edu

Study Contact Backup

Name: Joann Santmyer, RN

Phone Number: 410-614-3644

Email: GIClinicalTrials@jhmi.edu

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Newly diagnosed or clinically-suspected adenocarcinoma of the head, neck, or uncinate process of the pancreas
Tumor must be surgically resectable
ECOG Performance Status of 0 to 1
Adequate organ function as defined by study-specified laboratory tests
Must agree to use acceptable form of birth control

Received any type of anti-cancer treatment or immunotherapy for pancreas cancer
History of autoimmune disease (Graves or Hashimoto's disease, vitiligo, and type I diabetes are allowed)
Systemically steroid use within 14 days
Evidence of active infection
Pregnant or lactating
Diagnosed with another cancer or myeloproliferative disorder (some exceptions)
History of severe hypersensitivity reaction to any monoclonal antibody or known component of the study drugs
Known history of infection with HIV, hepatitis B, or hepatitis C
Oxygen saturation of <92% on room air by pulse oximetry
On home oxygen

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)
Bristol-Myers Squibb

Investigators

PRINCIPAL_INVESTIGATOR: Ana De Jesus-Acosta, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

Learn

Resources

PatientS

Caregivers

Clinical Trial Record