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 .
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
22
SBRT (6.6 Gy over 5 days) will be administered between 2 to 4 weeks after chemotherapy. (Prior to surgery)
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.
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.
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.
Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States
Study Drug-related Adverse Events
Number of participants who experienced study drug-related toxicities as defined by CTCAE v5.0
Time frame: Up to 18 months
Tumor Immune Response (CD8+ CD137+ Tumor Infiltration)
Number of participants who had \>80% increase of infiltration of CD8+CD137+ T cells into their tumors after treatment with SBRT and immunotherapy. Baseline biopsies were collected at time of fiducial placement for SBRT (after completion of chemotherapy) and post-treatment tumor was collected at time of surgical resection
Time frame: 7 months
Overall Survival (OS)
Number of months from start of immunotherapy until death from any cause
Time frame: 3 years
Metastasis Free Survival (MFS)
Number of months from the start of immunotherapy until first documented distant metastases on radiographic imaging or death from any cause, whichever occurs first.
Time frame: 3 years
Local Progression Free Survival (LPFS)
Number of months from the start of immunotherapy until first documented local progression on radiographic imaging or death from any cause, whichever occurs first. Local progression is defined as appearance of new lesions in the pancreas or surgical resection bed (for surgically resected patients) or clinically meaningful tumor growth in the primary pancreas tumor (for patients that were not surgically resectable).
Time frame: 3 years
Surgical Resectability Rate
Number of participants who are able to undergo successful tumor resection (as defined by R0 and R1 resection).
Time frame: 7 months
Pathological Response Rate
Number of participants who with a moderate, marked, or complete pathologic response after chemotherapy, SBRT, and one cycle of immunotherapy as determined by surgical margins and residual disease. Tumor response grading Complete response (grade 0): no viable residual cancer cells Marked response (grade 1): single cells or rare small groups of cancer cells Moderate response (grade 2): residual cancer outgrown by fibrosis Poor or no response (grade 3): extensive residual cancer
Time frame: 7 months
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