Comparing Neoadjuvant/Adjuvant GVAX Vs A MKRASvax Given With Anti-PD-1 And Anti-CD137 For Surgically Resectable Pancreatic Cancer

Study Overview

Comparing Neoadjuvant/Adjuvant GVAX vs a mKRASvax Given With Anti-PD-1 and Anti-CD137 for Surgically Resectable Pancreatic Cancer

The purpose of this study is to determine the optimal dose of AGEN2373 that is safe when given in combination with balstilimab and Pancreatic GVAX Whole Cell Vaccine and evaluate the safety and clinical activity of balstilimab and AGEN2373 in combination with GVAX (Arm 1) or mKRASvax (Arm 2) in surgically resectable pancreatic adenocarcinoma.

N/A

Pancreatic Cancer

DRUG: AGEN2373
DRUG: Balstilimab
DRUG: Cyclophosphamide
DRUG: GVAX
DRUG: AGEN2373 (RP2D)
DRUG: Balstilimab
DRUG: mKRASvax

J24146
IRB00465956 (OTHER Identifier) (OTHER: Johns Hopkins Medicine Internal Review Board)

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 2025-01-14	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-06-17
First Submitted that Met QC Criteria 2025-01-14	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-06-24
First Posted (ACTUAL) 2025-01-20	Results First Posted N/A	Last Verified 2025-06

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:
Non Randomized

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Arm 1 - AGEN2373/Balstilimab/Cyclophosphamide/GVAX	DRUG: AGEN2373 1. Up to 3 doses (1 mg/kg, 3 mg/kg, and 10 mg/kg) will be tested in Phase I to determine the dose to be used in Phase II. AGEN2373 will be administered as a 60 minute IV infusion (-5/+15 min) on Day 1 of each cycle for a total of 6 cycles of treatment. Cy DRUG: Balstilimab 1. 450 mg will be administered as a 30 minute IV Infusion (-5/+15 min) on day 1 of each cycle for a total of 6 cycles of treatment. Cycle 1 (14 days) is prior to surgical resection, Cycle 2 (14 days) is after surgery and prior to standard of care chemothe DRUG: Cyclophosphamide 1. 200 mg/m2 will be administered as a 30 minute IV infusion (-5/+15 min) on day 1 of each cycle for a total of 6 cycles of treatment. Cycle 1 (14 days) is prior to surgical resection, Cycle 2 (14 days) is after surgery and prior to standard of care chemo DRUG: GVAX 1. Vaccine (5 × 108 cells) will be administered on Day 2 of each cycle for a total of 6 cycles of treatment. Six intradermal injections will be given in the upper thighs and non-dominant arms. Cycle 1 (14 days) is prior to surgical resection, Cycle 2 (14
EXPERIMENTAL: Arm 2 - AGEN2373/Balstilimab/mKRASvax (1.8mg total peptides +0.5mg each poly-ICLC)	DRUG: AGEN2373 (RP2D) 1. Drug: Up to 3 doses (1 mg/kg, 3 mg/kg, and 10 mg/kg) will be administered as a 60 minute IV. Infusion (-5/+15 min) on Day 1 of each cycle for a total of 6 cycles of treatment. Cycle 1 (14 days) is prior to surgical resection, Cycle 2 (14 days) is after DRUG: Balstilimab 1. 450 mg will be administered as a 30 minute IV. Infusion (-5/+15 min) on day 1 of each cycle for a total of 6 cycles of treatment. Cycle 1 (14 days) is prior to surgical resection, Cycle 2 (14 days) is after surgery and prior to standard of care chemoth DRUG: mKRASvax 1. mKRASvax will be administered on Day 1 of each cycle and on Day 8 of Cycle 1 only. mKRASvax is given as 5 subcutaneous injections administered in the upper thighs and arms. Cycle 1 (14 days) is prior to surgical resection, Cycle 2 (14 days) is after su

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Arm 1 - AGEN2373/Balstilimab/Cyclophosphamide/GVAX

DRUG: AGEN2373

1. Up to 3 doses (1 mg/kg, 3 mg/kg, and 10 mg/kg) will be tested in Phase I to determine the dose to be used in Phase II. AGEN2373 will be administered as a 60 minute IV infusion (-5/+15 min) on Day 1 of each cycle for a total of 6 cycles of treatment. Cy

DRUG: Balstilimab

1. 450 mg will be administered as a 30 minute IV Infusion (-5/+15 min) on day 1 of each cycle for a total of 6 cycles of treatment. Cycle 1 (14 days) is prior to surgical resection, Cycle 2 (14 days) is after surgery and prior to standard of care chemothe

DRUG: Cyclophosphamide

1. 200 mg/m2 will be administered as a 30 minute IV infusion (-5/+15 min) on day 1 of each cycle for a total of 6 cycles of treatment. Cycle 1 (14 days) is prior to surgical resection, Cycle 2 (14 days) is after surgery and prior to standard of care chemo

DRUG: GVAX

1. Vaccine (5 × 108 cells) will be administered on Day 2 of each cycle for a total of 6 cycles of treatment. Six intradermal injections will be given in the upper thighs and non-dominant arms. Cycle 1 (14 days) is prior to surgical resection, Cycle 2 (14

EXPERIMENTAL: Arm 2 - AGEN2373/Balstilimab/mKRASvax (1.8mg total peptides +0.5mg each poly-ICLC)

DRUG: AGEN2373 (RP2D)

1. Drug: Up to 3 doses (1 mg/kg, 3 mg/kg, and 10 mg/kg) will be administered as a 60 minute IV. Infusion (-5/+15 min) on Day 1 of each cycle for a total of 6 cycles of treatment. Cycle 1 (14 days) is prior to surgical resection, Cycle 2 (14 days) is after

DRUG: Balstilimab

1. 450 mg will be administered as a 30 minute IV. Infusion (-5/+15 min) on day 1 of each cycle for a total of 6 cycles of treatment. Cycle 1 (14 days) is prior to surgical resection, Cycle 2 (14 days) is after surgery and prior to standard of care chemoth

DRUG: mKRASvax

1. mKRASvax will be administered on Day 1 of each cycle and on Day 8 of Cycle 1 only. mKRASvax is given as 5 subcutaneous injections administered in the upper thighs and arms. Cycle 1 (14 days) is prior to surgical resection, Cycle 2 (14 days) is after su

Primary Outcome Measures	Measure Description	Time Frame
Dose Limiting Toxicities in Phase I participants	Phase I participants will be evaluated for dose limiting toxicities (DLTs) during the first 14 day cycle and 14 days post-operatively for the purpose of determining the recommended phase II dose of AGEN2373 when given concurrently with balstilimab and cancer vaccination.	1 month
Number of participants experiencing Grade 3 or Higher study drug-related toxicities	Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0	2 years
Number of participants who form Intratumoral tertiary lymphoid structures (TLS)	Number of participants who form at least one tertiary lymphoid structure (TLS) following one cycle of study drugs. The presence of at least 50 CD20+ B cells and 50 CD3+ T cells in a ≥50 µM area of surgical tissue is considered "positive" for TLS.	2 weeks

Secondary Outcome Measures	Measure Description	Time Frame
Pathologic overall response rate (pORR)	Number of participants who have a pathologic response to the first dose of study drug as determined using surgically resected tissue and the College of American Pathologists (CAP) scoring system. A pathologic response is defined as CAP grade of 0-2. Possible CAP grades include grade 0: Complete Response/ No viable residual tumor; grade 1: Marked Response/ minimal residual cancer with single cells or small groups of cancer cells; grade 2: Moderate Response/ residual cancer outgrown by fibrosis; and grade 3: Poor or No response/ extensive residual cancer.	evaluated at time of surgery, approximately 2 weeks from first dose of study drug
CD3+CD8+CD137+ T cell density in Tumor Tissue	Number of CD3+CD8+CD137+ T cells found in resected surgical tissue by Immunohistochemistry (IHC).	evaluated at time of surgery, approximately 2 weeks from first dose of study drug
Change in peripheral interferon-gamma (IFNγ) producing mutant KRAS-specific T cells	Percent change in the number of IFNγ producing T cells at Cycle 2 Day 14 when compared with baseline. Number of IFNγ T cells will be assessed by ELISPOT.	13 weeks

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 Santmeyer, 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:

Have a newly diagnosed, biopsy-proven adenocarcinoma of the pancreas.
Tumor must be deemed resectable by the study team
Patient's acceptance to have a tumor biopsy.
Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1.
Patients must have adequate organ and marrow function defined by study-specified laboratory tests and procedures.
Women of childbearing potential (WOCBP) must have a negative serum pregnancy test.
For both Women and Men, must use acceptable form of birth control while on study.

Received any anti-pancreatic cancer therapy (symptomatic therapies are allowed), or any prior anti-cancer immunotherapy.
Diagnosed with another cancer whose natural history or treatment could interfere with safety or efficacy assessments on this study.
Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements.
Active autoimmune disease.
Systemic steroid therapy (> 10mg daily prednisone equivalent) or immunosuppressive therapy within 14 days of first dose of study drug administration.
Active infection requiring systemic therapy.
Known history of human immunodeficiency virus (HIV).
Active or chronic hepatitis B or hepatitis C.
Known active tuberculosis.
History of interstitial lung disease, non-infectious pneumonitis or uncontrolled lung diseases including pulmonary fibrosis, acute lung diseases, chronic obstructive pulmonary disease (COPD), asthma requiring medication, etc.
Prior allogeneic stem cell transplantation or organ transplantation.
Any major surgical procedure requiring general anesthesia ≤ 28 days before first dose of study drug.
Received a live vaccine ≤ 28 days before first dose of study drug.
History of severe hypersensitivity reaction to any monoclonal antibody
Concurrent participation in another therapeutic clinical study
Pregnant or breastfeeding

Collaborators and Investigators

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

Agenus Inc.
Lustgarten Foundation
Oncovir, Inc.

Investigators

PRINCIPAL_INVESTIGATOR: Eric Christenson, MD, SKCCC • Johns Hopkins Medical Institution

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

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