Trial Of Neoadjuvant And Adjuvant Nivolumab And BMS-813160 With Or Without GVAX For Locally Advanced Pancreatic Ductal Adenocarcinomas.

Study Overview

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

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 .

N/A

Locally Advanced Pancreatic Ductal Adenocarcinoma (PDAC)
Pancreatic Ductal Adenocarcinoma

RADIATION: Stereotactic Body Radiation (SBRT)
DRUG: Nivolumab
DRUG: CCR2/CCR5 dual antagonist
DRUG: GVAX

J18163
IRB00190660 (OTHER Identifier) (OTHER: JHMI IRB)

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 2018-12-05	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2024-12-05
First Submitted that Met QC Criteria 2018-12-05	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2024-12-10
First Posted (ACTUAL) 2018-12-06	Results First Posted N/A	Last Verified 2024-12

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:
Sequential

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Phase I - GVAX/Nivolumab/CCR2/CCR5 dual antagonist	RADIATION: Stereotactic Body Radiation (SBRT) SBRT (6.6 Gy over 5 days) will be administered between 2 to 4 weeks after chemotherapy. (Prior to surgery) DRUG: Nivolumab 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. DRUG: CCR2/CCR5 dual antagonist 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 DRUG: GVAX 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.
EXPERIMENTAL: Phase II - Arm A: Nivolumab/CCR2/CCR5 dual antagonist	RADIATION: Stereotactic Body Radiation (SBRT) SBRT (6.6 Gy over 5 days) will be administered between 2 to 4 weeks after chemotherapy. (Prior to surgery) DRUG: Nivolumab 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. DRUG: CCR2/CCR5 dual antagonist 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
EXPERIMENTAL: Phase II - Arm B: Nivolumab/GVAX/CCR2/CCR5 dual antagonist	RADIATION: Stereotactic Body Radiation (SBRT) SBRT (6.6 Gy over 5 days) will be administered between 2 to 4 weeks after chemotherapy. (Prior to surgery) DRUG: Nivolumab 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. DRUG: CCR2/CCR5 dual antagonist 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 DRUG: GVAX 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.

Participant Group/Arm

Intervention/Treatment

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

RADIATION: Stereotactic Body Radiation (SBRT)

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

DRUG: Nivolumab

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.

DRUG: CCR2/CCR5 dual antagonist

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

DRUG: GVAX

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.

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

RADIATION: Stereotactic Body Radiation (SBRT)

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

DRUG: Nivolumab

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.

DRUG: CCR2/CCR5 dual antagonist

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

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

RADIATION: Stereotactic Body Radiation (SBRT)

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

DRUG: Nivolumab

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.

DRUG: CCR2/CCR5 dual antagonist

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

DRUG: GVAX

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.

Primary Outcome Measures	Measure Description	Time Frame
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 Outcome Measures	Measure Description	Time Frame
Overall survival (OS)	Number of months from the time of Cycle 1, Day 1 of immunotherapy until death from any cause	3 years
Metastasis free survival (MFS)	Number of months from the time of Cycle 1, Day 1 of immunotherapy until first documented distant metastases on imaging per RECIST 1.1 or death from any cause, whichever occurs first.	3 years
Local progression free survival (LPFS) Time	Number of months from the time of Cycle 1, Day 1 of immunotherapy until first documented local progression or relapse from complete response on imaging (using RECIST 1.1 criteria and irRECIST criteria) or death from any cause, whichever occurs first.	3 years
Surgical Resectability Rate	Number of participants who are able to undergo successful tumor resection (as defined by R0 and R1 resection).	3 years
Pathological Response Rate	Number of participants who have a pathologic complete response as determined by surgical margins and residual disease.	3 years
Change in Quality of life score based on EORTC QLQ-C30/Pan26	Change in quality of life from baseline will be evaluated using the European Organization for Research and Treatment of Cancer core questionnaire, pancreatic cancer module (EORTC QLQ-C30/Pan26). The QLQ-C30 includes 30 questions assessing global health status/quality of life, function, and symptoms. The PAN26 module comprises of an additional 26 questions assessing pain, dietary changes, jaundice, altered bowel habit, emotional problems related to pancreatic cancer, and other symptoms (cachexia, indigestion, flatulence, dry mouth, taste changes). The score for each item ranges from 0-100, with a higher score reflecting a better level of functioning, a better quality of life, or a worse level of symptoms.	Baseline, 3 years

Contacts and Locations

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

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:

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.

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.
12-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.
Infection with HIV or hepatitis B or C.
Any concurrent malignancy other than non-melanoma skin cancer, non-invasive bladder cancer, early stage prostate cancer, or carcinoma in situ of the cervix.
Current or recent (within 3 months of study treatment administration) gastrointestinal disease that could impact the absorption of study treatment.
Any gastrointestinal surgery that is likely impact upon the absorption of study treatment.
Inability to tolerate oral medication.
Unable to have blood drawn.
Have had surgery within 28 days of the first dose of study medication.
Prior use of strong/moderate CYP3A4 inhibitors or inducers within 28 days of the first dose of BMS-813160.
Prior use of Class I antiarrhythmics within 28 days of first dose of study medication.
Has ascites requiring medical management.
Presence of duodenal or gastric invasion by the tumor.
Hypersensitivity reaction to any monoclonal antibody.
Known allergy or hypersensitivity to study drugs or any of their components of the study arm that participant is enrolling.
Woman who are pregnant or breastfeeding.
Patient is unwilling or unable to follow the study schedule for any reason.

Collaborators and Investigators

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

Bristol-Myers Squibb

Investigators

PRINCIPAL_INVESTIGATOR: Amol Narang, MD, Johns Hopkins Medical Institution

Publications

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