NCT05688215

Zimberelimab and Quemliclustat in Combination With Chemotherapy for the Treatment of Patients With Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma

A Pilot Study of Zimberelimab and Quemliclustat Combination With Chemotherapy in Patients With Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 56 (estimated)
• Sponsor: Jonsson Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

PRIMARY OBJECTIVES: I. To evaluate the safety, tolerability and resection rate (for borderline resectable pancreatic cancer \[BRPC\] cohort) or progression free survival (PFS) (for locally advanced pancreatic cancer \[LAPC\] cohort) in patients with borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC) treated with modified fluorouracil, irinotecan, leucovorin and oxaliplatin (mFOLFIRINOX), quemliclustat, and zimberelimab. II. To evaluate development of clinically relevant pancreatic fistula (for BRPC cohort) in the post-operative period after neoadjuvant treatment with mFOLFIRINOX, quemliclustat, and zimberelimab. SECONDARY OBJECTIVES: I. To estimate efficacy as measured by decreases in CA 19-9 and objective response rate (ORR) by imaging (unconfirmed complete and partial responses). II. To estimate the pathologic complete response rate (pCR) (for BRPC cohort) and overall survival (OS). EXPLORATORY OBJECTIVES: I. To evaluate the effects of zimberelimab, quemliclustat, and modified FOLFIRINOX (mFFX) on the tumor-stromal cells comparing pre-treatment core biopsies with operative specimens and on the effects on T cell infiltration, PD1 expression and the tumor microenvironment (TME). II. To investigate potential serum and tumor predictive biomarkers to predict response to experimental therapy. OUTLINE: Patients receive zimberelimab intravenously (IV), quemliclustat IV, oxaliplatin IV, leucovorin calcium IV, and inrinotecan IV on study. Patients undergo collection of blood samples and computed tomography (CT) throughout the trial. Patients with borderline-resectable pancreatic cancer undergo collection of tissue samples. Patients with locally advanced pancreatic cancer undergo core biopsy.

Conditions

• Borderline Resectable Pancreatic Adenocarcinoma
• Locally Advanced Pancreatic Ductal Adenocarcinoma

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo collection of blood and tissue samples
PROCEDURE	Computed Tomography	Undergo a CT scan
PROCEDURE	Core Biopsy	Undergo core biopsy
DRUG	Fluorouracil	Given IV
DRUG	Irinotecan	Given IV
DRUG	Leucovorin	Given IV
DRUG	Leucovorin Calcium	Given IV
DRUG	Oxaliplatin	Given IV
DRUG	Quemliclustat	Given intravenously (IV)
DRUG	Zimberelimab	Given IV

Timeline

• Start date: 2023-03-07
• Primary completion: 2026-12-01
• Completion: 2027-03-02
• First posted: 2023-01-18
• Last updated: 2026-01-15

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study