Modulation of the Gut Microbiome With Pembrolizumab Following Chemotherapy in Resectable Pancreatic Cancer

Pre-treatment tumor biopsy

"Patients will receive FOLFIRINOX chemotherapy every 2 weeks for 5 cycles. One cycle of mFOLFIRINOX = 14 days.~Cycles of mFOLFIRINOX are delivered as follows\*:~* Oxaliplatin: 85 mg/m2 IV over 2 hours on Day 1, followed by,~* Irinotecan: 150 mg/m2 IV over 90 minutes on Day 1, followed by,~* Leucovorin\*\*: 400 mg/m2 IV over 2 hours on Day 1, followed by,~* 5FU: 2400 mg/m2 IV over 46-48 hours on Days 1-3"

Ciprofloxacin and metronidazole will be initiated 7 days following 5th dose of FOLFIRINOX. Subjects will self-administer ciprofloxacin 500mg PO BID on days 1-21. Participants will be instructed to take the antibiotics with food to minimize stomach upset and to administer at the same time each day. Treatment with antibiotics will continue for 21 days unless there is unacceptable toxicity or disease progression. Subjects will record date, time and number of tablets they take on provided drug diaries.

Ciprofloxacin and metronidazole will be initiated 7 days following 5th dose of FOLFIRINOX. Subjects will self-administer metronidazole 500mg PO every 8 hours on days 1-21. Participants will be instructed to take the antibiotics with food to minimize stomach upset and to administer at the same time each day. Treatment with antibiotics will continue for 21 days unless there is unacceptable toxicity or disease progression. Subjects will record date, time and number of tablets they take on provided drug diaries.

Pembrolizumab will be initiated 7 days post initiation of antibiotics. Subjects will receive a flat dose of pembrolizumab 200mg IV over 30 minutes.

Following completion of 21 days of antibiotics, participant will undergo repeat imaging studies. If there is no progressive disease which renders participant surgically unresectable (based on NCCN guidelines 2.2021), subject will undergo definitive surgical resection.