This phase I/II study tests how well zimberelimab and quemliclustat work in combination with chemotherapy (mFOLFIRINOX) in treating patients pancreatic adenocarcinoma that may or may not be able to be removed by surgery (borderline resectable) or that has spread to nearby tissue or lymph nodes (locally advanced). Immunotherapy with monoclonal antibodies, such as zimberelimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Quemliclustat acts as a blocker for adenosine. Adenosine is a chemical produced in the body that can lead to a decrease in the immune system's response towards cancer. Quemliclustat has the potential to decrease the amount of adenosine, allowing the immune system to recognize and act against the cancer. Chemotherapy drugs, such as oxaliplatin, irinotecan, leucovorin, and fluorouracil, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy in combination with zimberelimab and quemliclustat may kill more cancer cells than chemotherapy alone.
Male or female >= 18 years of age and willing and able to provide informed consent
Borderline resectable disease. There are multiple definitions of borderline resectable PDAC including the MD Anderson definition and the criteria developed during the Consensus Conference sponsored by the American Hepato-Pancreato-Biliary Association, Society of Surgical Oncology, and Society for Surgery of the Alimentary Tract. Borderline resectable PDAC cases will be identified per the definition developed in the currently running inter-group pilot trial for borderline resectable pancreatic cancer (NCT01821612). Per this trial, borderline resectable PDAC is defined as the presence of any one or more of the following on CT;
An interface between the primary tumor and the superior mesenteric vein or portal vein (SMV-PV) measuring >= 180 degrees of the circumference of the vessel wall
Short-segment occlusion of the SMV-PV with normal vein above and below the level of obstruction that is amenable to resection and venous reconstruction
Recurrent or metastatic pancreatic adenocarcinoma
Peripheral neuropathy > grade 2
Known status of human immunodeficiency virus (HIV) which is not well-controlled (CD4 <300) at the time of study eligibility. Patients with controlled and treated HIV/Hepatitis C virus (HCV) and an undetectable viral load are allowed
Untreated Hepatitis B infection: Patient has known active hepatitis B virus (HBV) or hepatitis C virus (HCV), or Human immunodeficiency virus (HIV) infection (testing is not mandatory, unless required by local regulation)
Single group
Biospecimen Collection
Procedure/SurgeryUndergo collection of blood and tissue samples
Computed Tomography
Procedure/SurgeryUndergo a CT scan
Core Biopsy
Procedure/SurgeryUndergo core biopsy
Fluorouracil
DrugGiven IV
Irinotecan
DrugGiven IV
Leucovorin
DrugGiven IV
Leucovorin Calcium
DrugGiven IV
Oxaliplatin
DrugGiven IV
Quemliclustat
DrugGiven intravenously (IV)
Zimberelimab
DrugGiven IV
Incidence of adverse events (BPRC Cohort)
All safety summaries and analyses will be based upon the Safety Population, as defined in this study protocol, will include all randomized participants who receive at least 1 dose of any study drug. Overall exposure to study drug, the numbers of participants completing each cycle, and the dose intensity will be summarized using descriptive statistics. The number of participants with any dose adjustment will be presented for entire treatment period as well as for each cycle. The number of participants with dose reductions, dose delays, or dose omissions will also be summarized, as will the reasons for dose adjustments. Adverse events (AEs) and serious adverse events (SAEs) will be reported using Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 terminology and severity.
Resection rate (BPRC Cohort)
Simon's two-stage design will be used to demonstrate the resection rate is greater than 50%.
Progression free survival (PFS) (LAPC Cohort)
Descriptive statistics with frequency and proportion will be used to summarize R0 resection rate and PFS. Kaplan-Meier methods will be used to analyze PFS and to generate 95% confidence interval (CI).
Number of participants who develop clinically relevant pancreatic fistula (BPRC Cohort)
Change in CA 19-9 levels
Objective response rate (ORR)
Descriptive statistics with frequency and proportion used to analyze. Assessed by imaging.
Pathologic complete response rate (pCR) (BPRC Cohort)
Overall survival (OS)
Descriptive statistics with frequency and proportion will be used to analyze.
Click on the lead sponsor to view all of their trials.
Jonsson Comprehensive Cancer Center
Lead sponsor
Arcus Biosciences, Inc.
Collaborator
