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

NCT06782932 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: J24146IRB00465956
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pancreatic Cancer

Keywords

Balstilimab; AGEN2373; KRAS peptide vaccine; peptide vaccine; Poly-ICLC; GVAX; Cyclophosphamide; Immunotherapy; Anti-PD-1 (anti-check point inhibitor); PD-L1 (check point inhibitor); Anti-CD137; Cancer vaccine; Pancreatic Cancer; Pancreatic Ductal Adenocarcinoma (PDAC); Adenocarcinoma; Carcinoma; Pancreas; mKRASvax

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (3)

• Pathologic overall response rate (pORR)

  evaluated at time of surgery, approximately 2 weeks from first dose of study drug

• CD3+CD8+CD137+ T cell density in Tumor Tissue

  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

  13 weeks

Study Arms (2)

Arm 1 - AGEN2373/Balstilimab/Cyclophosphamide/GVAX

EXPERIMENTAL

Drug: AGEN2373; Drug: Balstilimab; Drug: Cyclophosphamide; Drug: GVAX

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

EXPERIMENTAL

Drug: AGEN2373 (RP2D); Drug: Balstilimab; Drug: mKRASvax

Interventions

AGEN2373 DRUG

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. 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. 2. Drug: 1 mg/kg, 3 mg/kg, and 10 mg/kg IV

Arm 1 - AGEN2373/Balstilimab/Cyclophosphamide/GVAX

Balstilimab DRUG

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 chemotherapy, and Cycles 3-6 (21 days) are given after completion of chemotherapy. 2. Drug: 450 mg IV

Also known as: AGEN2034, anti-PD-1 antibody

Arm 1 - AGEN2373/Balstilimab/Cyclophosphamide/GVAX

Cyclophosphamide DRUG

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 chemotherapy, and Cycles 3-6 (21 days) are given after completion of chemotherapy. 2. Drug: 200 mg/m2 IV

Also known as: Cy

Arm 1 - AGEN2373/Balstilimab/Cyclophosphamide/GVAX

GVAX DRUG

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 days) is after surgery and prior to standard of care chemotherapy, and Cycles 3-6 (21 days) are given after completion of chemotherapy. 2. Drug: GVAX

Also known as: PANC 10.05 pcDNA-1/GM-Neo vaccine and PANC 6.03 pcDNA-1/GM-Neo vaccine

Arm 1 - AGEN2373/Balstilimab/Cyclophosphamide/GVAX

AGEN2373 (RP2D) DRUG

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 surgery and prior to standard of care chemotherapy, and Cycles 3-6 (21 days) are given after completion of chemotherapy. 2. Drug: 1 mg/kg, 3 mg/kg, and 10 mg/kg IV

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

mKRASvax DRUG

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 surgery and prior to standard of care chemotherapy, and Cycles 3-6 (21 days) are given after completion of chemotherapy. 2. 0.3 mg per peptide vaccine + 0.5mg Poly-ICLC

Also known as: mutant KRAS peptide vaccine with Hiltonol® (Poly-ICLC)

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Agenus Inc.: collaborator
• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Lustgarten Foundation: collaborator
• Oncovir, Inc.: collaborator

Study Sites (1)

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms; Adenocarcinoma; Carcinoma

Interventions

balstilimab; Cyclophosphamide; poly ICLC

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Eric Christenson, MD

  SKCCC • Johns Hopkins Medical Institution

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Colleen Apostol, RN

CONTACT

410-614-3644; GIClinicalTrials@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2025
• First Posted: January 20, 2025
• Study Start: May 27, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: December 3, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)