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

NCT05688215 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 22-001565NCI-2022-10208
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Borderline Resectable Pancreatic Adenocarcinoma; Locally Advanced Pancreatic Ductal Adenocarcinoma

Outcome Measures

Primary Outcomes (4)

• 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.

  From baseline measurement to 90 days after the last dose of study treatment.

• Resection rate (BPRC Cohort)

  Simon's two-stage design will be used to demonstrate the resection rate is greater than 50%.

  Up to 2 years

• 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).

  Up to 2 years

• Number of participants who develop clinically relevant pancreatic fistula (BPRC Cohort)

  Up to 2 years

Secondary Outcomes (4)

• Change in CA 19-9 levels

  Up to 30 days after last study drug administration

• Objective response rate (ORR)

  Up to 2 years

• Pathologic complete response rate (pCR) (BPRC Cohort)

  Up to 2 years

• Overall survival (OS)

  Up to 2 years

Study Arms (1)

Treatment (zimberelimab, quemliclustat, chemotherapy)

EXPERIMENTAL

Patients receive zimberelimab IV, quemliclustat IV, oxaliplatin IV, leucovorin calcium IV, and inrinotecan IV on study. Patients undergo collection of blood samples and CT throughout the trial. Patients with borderline-resectable pancreatic cancer undergo collection of tissue samples. Patients with locally advanced pancreatic cancer undergo core biopsy.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Core Biopsy; Drug: Fluorouracil; Drug: Irinotecan; Drug: Leucovorin; Drug: Leucovorin Calcium; Drug: Oxaliplatin; Drug: Quemliclustat; Drug: Zimberelimab

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of blood and tissue samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (zimberelimab, quemliclustat, chemotherapy)

Computed Tomography PROCEDURE

Undergo a CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan, tomography

Treatment (zimberelimab, quemliclustat, chemotherapy)

Core Biopsy PROCEDURE

Undergo core biopsy

Also known as: BIOPSY, CORE, CNB, Core Needle, Core Needle Biopsy, Needle Biopsy

Treatment (zimberelimab, quemliclustat, chemotherapy)

Fluorouracil DRUG

Given IV

Also known as: 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-Fu, 5FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757

Treatment (zimberelimab, quemliclustat, chemotherapy)

Irinotecan DRUG

Given IV

Treatment (zimberelimab, quemliclustat, chemotherapy)

Leucovorin DRUG

Given IV

Also known as: Folinic acid

Treatment (zimberelimab, quemliclustat, chemotherapy)

Leucovorin Calcium DRUG

Given IV

Also known as: Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate, Calcium Leucovorin, Calfolex, Calinat, Cehafolin, Citofolin, Citrec, Citrovorum Factor, Cromatonbic Folinico, Dalisol, Disintox, Divical, Ecofol, Emovis, Factor, Citrovorum, Flynoken A, Folaren, Folaxin, FOLI-cell, Foliben, Folidan, Folidar, Folinac, Folinate Calcium, folinic acid, Folinic Acid Calcium Salt Pentahydrate, Folinoral, Folinvit, Foliplus, Folix, Imo, Lederfolat, Lederfolin, Leucosar, leucovorin, Rescufolin, Rescuvolin, Tonofolin, Wellcovorin

Treatment (zimberelimab, quemliclustat, chemotherapy)

Oxaliplatin DRUG

Given IV

Also known as: 1-OHP, Ai Heng, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, SR-96669

Treatment (zimberelimab, quemliclustat, chemotherapy)

Quemliclustat DRUG

Given intravenously (IV)

Also known as: AB 680, AB-680, AB680, CD73 Inhibitor AB680

Treatment (zimberelimab, quemliclustat, chemotherapy)

Zimberelimab DRUG

Given IV

Also known as: AB 122, AB-122, AB122, Anti-PD-1 Monoclonal Antibody GLS-010, GLS 010, GLS-010, GLS010, WBP-3055

Treatment (zimberelimab, quemliclustat, chemotherapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female \>= 18 years of age and willing and able to provide informed consent
• Previously untreated cytologically or histologically confirmed pancreatic adenocarcinoma with one of the following:
• 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
• Short segment interface (of any degree) between tumor and hepatic artery with normal artery proximal and distal to the interface that is amenable to resection and reconstruction
• An interface between the tumor and SMA measuring \< 180 degrees of the circumference of the vessel wall
• Locally advanced disease. Multiple guidelines defining locally advanced PDAC have been developed, including the MD Anderson definition, the National Comprehensive Cancer Network (NCCN) definition, as well as 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. Locally advanced PDAC cases will be identified per the definition developed by the Alliance for Clinical Trials in Oncology. Per this definition, locally advanced PDAC is defined as presence of any one or more of the following on CT;
• Occlusion of the SMV-PV that is not amenable to resection and venous reconstruction
• Interface between tumor and hepatic artery that is not amenable to resection and reconstruction
• Interface between the tumor and SMA measuring \> 180 degrees of the circumference of the vessel wall
• Interface between the tumor and celiac axis measuring \> 180 degrees of the circumference of the vessel wall
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
• Platelets \>= 100 x 10\^9/L

You may not qualify if:

• 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)
• Participants with resolved or treated HCV (ie, HCV antibody positive but undetectable HCV ribonucleic acid \[RNA\]) will not be excluded from this study
• Underlying medical conditions that, in the Investigator's or Sponsor's opinion, will make the administration of Investigational products (IPs) hazardous, including but not limited to:
• Interstitial lung disease, including history of interstitial lung disease or non-infectious pneumonitis (lymphangitic spread of non-small cell lung cancer (NSCLC) is not disqualifying)
• Active viral, bacterial, or fungal infections requiring parenteral treatment within 14 days of the initiation of the IP
• Active infection or antibiotics within 48 hours prior to study screening
• Clinically significant cardiovascular disease
• A condition or unresolved adverse event (AE) from a prior investigational drug that may obscure the interpretation of toxicity determination or AEs
• History of prior solid-organ transplantation
• Currently active second primary malignancy or history of malignancy less than 5 years prior to the time of study eligibility (Patients with history of skin cancers excluding melanoma will be eligible for participation)
• Serious medical comorbidities such as New York Heart Association Class III/IV cardiac disease, uncontrolled cardiac arrhythmias, myocardial infarction over the past 12 months
• Known, existing uncontrolled coagulopathy. Patients who have had a venous thromboembolic event (e.g., pulmonary embolism or deep vein thrombosis) requiring anticoagulation are eligible IF: they are appropriately anticoagulated and have not had a Grade 2 or greater bleeding episode in the 3 weeks before Day 1

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• Arcus Biosciences, Inc.: collaborator

Study Sites (1)

Yonemoto,Lisa

Los Angeles, California, 90095, United States

RECRUITING

MeSH Terms

Interventions

Specimen Handling; Biopsy, Needle; Biopsy, Large-Core Needle; Fluorouracil; dehydroftorafur; Irinotecan; Leucovorin; Oxaliplatin; quemliclustat; zimberelimab

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Biopsy; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Punctures; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Study Officials

• Zev A Wainberg

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lisa Yonemoto

CONTACT

3105824069; LYonemoto@mednet.ucla.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2023
• First Posted: January 18, 2023
• Study Start: March 7, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): March 2, 2027
• Last Updated: January 15, 2026

Record last verified: 2025-04

Locations

US (1)