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

A Pilot Study Comparing Neoadjuvant and Adjuvant GVAX vs a Mutated KRAS Peptide Vaccine Given With Anti-PD-1 and Anti-CD137 for the Treatment of Surgically Resectable Pancreatic Adenocarcinoma

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.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: AGEN2373; Drug: Balstilimab; Drug: Cyclophosphamide; Drug: GVAX; Drug: Balstilimab; Drug: AGEN2373 (RP2D); Drug: mKRASvax

• Study Type: Interventional
• Enrollment (Estimated): 38
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Colleen Apostol, RN; Phone Number: 410-614-3644; Email: GIClinicalTrials@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
      • Principal Investigator: Eric Christenson, MD
      • Contact: Colleen Apostol, RN; Phone Number: 410-614-3644; Email: GIClinicalTrials@jhmi.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1 - AGEN2373/Balstilimab/Cyclophosphamide/GVAX	Drug: AGEN2373; 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. Cycle 1 (14 days) is prior to surgical resection, Cycle 2 (14 days) is after surgery and prior to standard of care chemotherapy, and Cycles 3-6 (21 days) are given after completion of chemotherapy.; Drug: 1 mg/kg, 3 mg/kg, and 10 mg/kg IV; Drug: Balstilimab; 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 chemotherapy, and Cycles 3-6 (21 days) are given after completion of chemotherapy.; Drug: 450 mg IV; Other Names: AGEN2034, anti-PD-1 antibody; Drug: Cyclophosphamide; 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 chemotherapy, and Cycles 3-6 (21 days) are given after completion of chemotherapy.; Drug: 200 mg/m2 IV; Other Names: Cy; Drug: GVAX; 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 days) is after surgery and prior to standard of care chemotherapy, and Cycles 3-6 (21 days) are given after completion of chemotherapy.; Drug: GVAX; Other Names: PANC 10.05 pcDNA-1/GM-Neo vaccine and PANC 6.03 pcDNA-1/GM-Neo vaccine; Drug: Balstilimab; 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 chemotherapy, and Cycles 3-6 (21 days) are given after completion of chemotherapy.; Drug: 450 mg IV; Other Names: AGEN2034, anti-PD-1 antibody
Experimental: Arm 2 - AGEN2373/Balstilimab/mKRASvax (1.8mg total peptides +0.5mg each poly-ICLC)	Drug: Balstilimab; 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 chemotherapy, and Cycles 3-6 (21 days) are given after completion of chemotherapy.; Drug: 450 mg IV; Other Names: AGEN2034, anti-PD-1 antibody; Drug: Balstilimab; 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 chemotherapy, and Cycles 3-6 (21 days) are given after completion of chemotherapy.; Drug: 450 mg IV; Other Names: AGEN2034, anti-PD-1 antibody; Drug: AGEN2373 (RP2D); 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 surgery and prior to standard of care chemotherapy, and Cycles 3-6 (21 days) are given after completion of chemotherapy.; Drug: 1 mg/kg, 3 mg/kg, and 10 mg/kg IV; Drug: mKRASvax; 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 surgery and prior to standard of care chemotherapy, and Cycles 3-6 (21 days) are given after completion of chemotherapy.; 0.3 mg per peptide vaccine + 0.5mg Poly-ICLC; Other Names: mutant KRAS peptide vaccine with Hiltonol® (Poly-ICLC)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Lustgarten Foundation; Agenus Inc.; Oncovir, Inc.
• Investigators: Principal Investigator: Eric Christenson, MD, SKCCC • Johns Hopkins Medical Institution

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: January 14, 2025
• First Submitted That Met QC Criteria: January 14, 2025
• First Posted (Actual): January 20, 2025

Study Record Updates

• Last Update Posted (Estimated): December 3, 2025
• Last Update Submitted That Met QC Criteria: December 1, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Carcinoma; Immunotherapy; Adenocarcinoma; Pancreatic Cancer; Poly-ICLC; Cyclophosphamide; Pancreas; Cancer vaccine; Balstilimab; GVAX; peptide vaccine; Anti-CD137; Pancreatic Ductal Adenocarcinoma (PDAC); Anti-PD-1 (anti-check point inhibitor); PD-L1 (check point inhibitor); AGEN2373; KRAS peptide vaccine; mKRASvax
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Neoplasms, Glandular and Epithelial; Carcinoma; Pancreatic Neoplasms; Adenocarcinoma; Organic Chemicals; Hydrocarbons; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cyclophosphamide; balstilimab; poly ICLC
• Other Study ID Numbers: J24146; IRB00465956 (Other Identifier: Johns Hopkins Medicine Internal Review Board)

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: Yes
• Studies a U.S. FDA-regulated device product: No