Trial of Neoadjuvant and Adjuvant Nivolumab and BMS-813160 With or Without GVAX for Locally Advanced Pancreatic Ductal Adenocarcinomas.

NCT03767582 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: J18163IRB00190660
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate if the combination of nivolumab and a CCR2/CCR5 dual antagonist (BMS-813160) with GVAX is safe in patients with locally advanced pancreatic cancer (LAPC) who have received chemotherapy and radiotherapy, and to see if this combination therapy enhances the infiltration of CD8+CD137+ cells in PDACs .

Conditions

Pancreatic Ductal Adenocarcinoma; Locally Advanced Pancreatic Ductal Adenocarcinoma (PDAC)

Keywords

GVAX; Nivolumab; CCR2/CCR5 dual antagonist; Anti-PD-1; Cancer vaccine; Monoclonal antibody; Checkpoint inhibitor; Myeloid modulating agent; Immunotherapy; Neoadjuvant chemotherapy; Stereotactic body radiation therapy; SBRT; Pancreatic cancer; Pancreatic Ductal Adenocarcinoma; PDAC; Locally advanced pancreatic ductal adenocarcinoma; LAPC

Outcome Measures

Primary Outcomes (2)

• Number of Participants experiencing study drug-related toxicities

  Number of participants who experienced study drug-related toxicities as defined by CTCAE v5.0

  3 years

• Percentage of participants treated with immunotherapy who achieve an immune response

  Percentage of participants who have \>80% increase of infiltration of CD8+CD137+ T cells into the pancreatic ductal adenocarcinoma after treatment with immunotherapy compared to baseline before treatment.

  3 years

Secondary Outcomes (6)

• Overall survival (OS)

  3 years

• Metastasis free survival (MFS)

  3 years

• Local progression free survival (LPFS) Time

  3 years

• Surgical Resectability Rate

  3 years

• Pathological Response Rate

  3 years

Study Arms (3)

Phase I - GVAX/Nivolumab/CCR2/CCR5 dual antagonist

EXPERIMENTAL

Radiation: Stereotactic Body Radiation (SBRT); Drug: Nivolumab; Drug: CCR2/CCR5 dual antagonist; Drug: GVAX

Phase II - Arm A: Nivolumab/CCR2/CCR5 dual antagonist

EXPERIMENTAL

Radiation: Stereotactic Body Radiation (SBRT); Drug: Nivolumab; Drug: CCR2/CCR5 dual antagonist

Phase II - Arm B: Nivolumab/GVAX/CCR2/CCR5 dual antagonist

EXPERIMENTAL

Radiation: Stereotactic Body Radiation (SBRT); Drug: Nivolumab; Drug: CCR2/CCR5 dual antagonist; Drug: GVAX

Interventions

Stereotactic Body Radiation (SBRT) RADIATION

SBRT (6.6 Gy over 5 days) will be administered between 2 to 4 weeks after chemotherapy. (Prior to surgery)

Phase I - GVAX/Nivolumab/CCR2/CCR5 dual antagonist; Phase II - Arm A: Nivolumab/CCR2/CCR5 dual antagonist; Phase II - Arm B: Nivolumab/GVAX/CCR2/CCR5 dual antagonist

Nivolumab DRUG

Nivolumab (480 mg) will be administered IV over 30 minutes, on day 1 of cycle 1 (within 1 to 2 weeks after SBRT prior to surgery). Post - surgery Nivolumab will be given on Day 1 of cycles 2-5. Cycles are 4 weeks long.

Also known as: OPDIVO

Phase I - GVAX/Nivolumab/CCR2/CCR5 dual antagonist; Phase II - Arm A: Nivolumab/CCR2/CCR5 dual antagonist; Phase II - Arm B: Nivolumab/GVAX/CCR2/CCR5 dual antagonist

CCR2/CCR5 dual antagonist DRUG

CCR2/CCR5 dual antagonist (150 mg capsules) will be administered orally twice a day, on days 1-28 of cycle 1 (within 1 to 2 weeks after SBRT prior to surgery). Post - surgery CCR2/CCR5 dual antagonist will be given daily on cycles 2-5. Cycles are 4 weeks long.

Also known as: BMS-813160

Phase I - GVAX/Nivolumab/CCR2/CCR5 dual antagonist; Phase II - Arm A: Nivolumab/CCR2/CCR5 dual antagonist; Phase II - Arm B: Nivolumab/GVAX/CCR2/CCR5 dual antagonist

GVAX DRUG

Vaccine (5x10\^8 cells) will be administered on day 2 of cycle 1 (within 1 to 2 weeks after SBRT prior to surgery). Post - surgery GVAX will be given on Day 2 of cycles 2-5. Cycles are 4 weeks long. Six intradermal injections every 4 weeks.

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

Phase I - GVAX/Nivolumab/CCR2/CCR5 dual antagonist; Phase II - Arm B: Nivolumab/GVAX/CCR2/CCR5 dual antagonist

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years.
• Patients with histologically- or cytologically-proven, surgically unresectable, locally advanced pancreatic adenocarcinoma.
• If the patient does not have a diagnostic biopsy that is adequate for review at our institution, the patient must agree to a research core biopsy to be performed at Johns Hopkins.
• If the patient's available imaging is not adequate for review by our institution, the patient must agree to a repeat imaging to be performed at Johns Hopkins.
• Patients cannot have had any prior therapy for the locally advanced pancreatic adenocarcinoma.
• ECOG performance status 0 or 1
• Life expectancy greater than 3 months.
• Able to swallow pills or capsules.
• Patient must have adequate organ function defined by the study-specified laboratory tests.
• Patients must be eligible to receive FOLFIRINOX-based chemotherapy.
• Patients must be willing to be treated with stereotactic body radiation therapy (SBRT) only at Johns Hopkins Hospital.
• Patients must be willing to undergo a core biopsy of the pancreatic cancer.
• Patients must be willing to undergo a biopsy of the pancreatic cancer if the patient is not deemed a surgical candidate during the pre-surgical evaluation.
• Must use acceptable form of birth control while on study.
• Ability to understand and willingness to sign a written informed consent document.

You may not qualify if:

• Have had non-FOLFIRINOX-based chemotherapy for the pancreatic cancer.
• Have received any anti-neoplastic biologics, vaccines or hormonal treatment, including investigational drugs, within 28 days of the first dose of study.
• History of past treatment with immunotherapy agents prior to initial enrollment into this study (including, but not limited to: IL-2, interferon, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, anti-CTLA-4 or anti-CCR2/5 drugs).
• Have had prior organ or tissue allograft or allogeneic bone marrow transplantation, including corneal transplants.
• Is currently participating or has participated in a study of an investigational agent or using an investigational device for the treatment of cancer.
• Current use of immunosuppressive medications within 14 days prior to study medications.
• Have received any vaccine within 14 days prior to study medications.
• Receiving growth factors including, but not limited to, granulocyte-colony stimulating factor (G-CSF), GM-CSF, erythropoietin, within 14 days of the first dose of study medication.
• History of any autoimmune disease. Patients with thyroid disease will be allowed.
• Has a history of (non-infectious) pneumonitis or current pneumonitis.
• Has a pulse oximetry \< 92% on room air.
• Requires the use of home oxygen.
• Patients with uncontrolled intercurrent illness including, but not limited to, myocardial infarction or stroke/transient ischemic attack within the past 6 months, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• lead electrocardiogram with QRS ≥ 120 msec, except right bundle branch block ; QTcF (QT corrected for heart rate using Fridericia's method) ≥ 480 msec, except right bundle branch block
• Has an active infection requiring systemic therapy.

Sponsors & Collaborators

• Bristol-Myers Squibb: collaborator
• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Radiosurgery; Nivolumab; BMS-813160

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Amol Narang, MD

  Johns Hopkins Medical Institution

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 5, 2018
• First Posted: December 6, 2018
• Study Start: December 12, 2019
• Primary Completion: February 1, 2025
• Study Completion: February 1, 2025
• Last Updated: December 3, 2025

Record last verified: 2025-12

Locations

US (1)