Trial Title:
Zimberelimab and Quemliclustat in Combination with Chemotherapy for the Treatment of Patients with Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma
NCT ID:
NCT05688215
Condition:
Borderline Resectable Pancreatic Adenocarcinoma
Locally Advanced Pancreatic Ductal Adenocarcinoma
Conditions: Official terms:
Adenocarcinoma
Calcium, Dietary
Leucovorin
Folic Acid
Oxaliplatin
Fluorouracil
Irinotecan
Quemliclustat
Calcium
Levoleucovorin
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo collection of blood and tissue samples
Arm group label:
Treatment (zimberelimab, quemliclustat, chemotherapy)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo a CT scan
Arm group label:
Treatment (zimberelimab, quemliclustat, chemotherapy)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Procedure
Intervention name:
Core Biopsy
Description:
Undergo core biopsy
Arm group label:
Treatment (zimberelimab, quemliclustat, chemotherapy)
Other name:
BIOPSY, CORE
Other name:
CNB
Other name:
Core Needle
Other name:
Core Needle Biopsy
Other name:
Needle Biopsy
Intervention type:
Drug
Intervention name:
Fluorouracil
Description:
Given IV
Arm group label:
Treatment (zimberelimab, quemliclustat, chemotherapy)
Other name:
5 Fluorouracil
Other name:
5 Fluorouracilum
Other name:
5 FU
Other name:
5-Fluoro-2,4(1H, 3H)-pyrimidinedione
Other name:
5-Fluorouracil
Other name:
5-Fluracil
Other name:
5-Fu
Other name:
5FU
Other name:
AccuSite
Other name:
Carac
Other name:
Fluoro Uracil
Other name:
Fluouracil
Other name:
Flurablastin
Other name:
Fluracedyl
Other name:
Fluracil
Other name:
Fluril
Other name:
Fluroblastin
Other name:
Ribofluor
Other name:
Ro 2-9757
Other name:
Ro-2-9757
Intervention type:
Drug
Intervention name:
Irinotecan
Description:
Given IV
Arm group label:
Treatment (zimberelimab, quemliclustat, chemotherapy)
Intervention type:
Drug
Intervention name:
Leucovorin
Description:
Given IV
Arm group label:
Treatment (zimberelimab, quemliclustat, chemotherapy)
Other name:
Folinic acid
Intervention type:
Drug
Intervention name:
Leucovorin Calcium
Description:
Given IV
Arm group label:
Treatment (zimberelimab, quemliclustat, chemotherapy)
Other name:
Adinepar
Other name:
Calcifolin
Other name:
Calcium (6S)-Folinate
Other name:
Calcium Folinate
Other name:
Calcium Leucovorin
Other name:
Calfolex
Other name:
Calinat
Other name:
Cehafolin
Other name:
Citofolin
Other name:
Citrec
Other name:
Citrovorum Factor
Other name:
Cromatonbic Folinico
Other name:
Dalisol
Other name:
Disintox
Other name:
Divical
Other name:
Ecofol
Other name:
Emovis
Other name:
Factor, Citrovorum
Other name:
Flynoken A
Other name:
Folaren
Other name:
Folaxin
Other name:
FOLI-cell
Other name:
Foliben
Other name:
Folidan
Other name:
Folidar
Other name:
Folinac
Other name:
Folinate Calcium
Other name:
folinic acid
Other name:
Folinic Acid Calcium Salt Pentahydrate
Other name:
Folinoral
Other name:
Folinvit
Other name:
Foliplus
Other name:
Folix
Other name:
Imo
Other name:
Lederfolat
Other name:
Lederfolin
Other name:
Leucosar
Other name:
leucovorin
Other name:
Rescufolin
Other name:
Rescuvolin
Other name:
Tonofolin
Other name:
Wellcovorin
Intervention type:
Drug
Intervention name:
Oxaliplatin
Description:
Given IV
Arm group label:
Treatment (zimberelimab, quemliclustat, chemotherapy)
Other name:
1-OHP
Other name:
Ai Heng
Other name:
Aiheng
Other name:
Dacotin
Other name:
Dacplat
Other name:
Diaminocyclohexane Oxalatoplatinum
Other name:
Eloxatin
Other name:
Eloxatine
Other name:
JM-83
Other name:
Oxalatoplatin
Other name:
Oxalatoplatinum
Other name:
RP 54780
Other name:
RP-54780
Other name:
SR-96669
Intervention type:
Drug
Intervention name:
Quemliclustat
Description:
Given intravenously (IV)
Arm group label:
Treatment (zimberelimab, quemliclustat, chemotherapy)
Other name:
AB 680
Other name:
AB-680
Other name:
AB680
Other name:
CD73 Inhibitor AB680
Intervention type:
Drug
Intervention name:
Zimberelimab
Description:
Given IV
Arm group label:
Treatment (zimberelimab, quemliclustat, chemotherapy)
Other name:
AB 122
Other name:
AB-122
Other name:
AB122
Other name:
Anti-PD-1 Monoclonal Antibody GLS-010
Other name:
GLS 010
Other name:
GLS-010
Other name:
GLS010
Other name:
WBP-3055
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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
- Hemoglobin >= 9 g/dL
- Serum creatinine (sCr) =< 1.5 x upper limit of normal (ULN) or Creatinine clearance
(Ccr) >= 40 mL/min (as calculated by Modified Cockcroft-Gault formula)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
(AST/[SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate
transaminase [SGPT]) =< 2.5 X ULN
- Women with no childbearing potential because of surgery or who are at least 1 year
postmenopausal (ie, 12 months post last menstrual period) or with menopause
confirmed by follicle-stimulating hormone testing
- Women of childbearing potential must use an effective nonhormonal method of
contraception (intrauterine device or intrauterine system; condom or occlusive cap
[diaphragm or cervical or vault caps] with spermicidal foam or gel or film or cream
or suppository; or vasectomized male partner if he is the sole partner of that
participant) for the duration of the study and for up to 6 months after the last
dose of zimberelimab or quemliclustat
- Male participants must use an effective method of contraception (condom or occlusive
cap [diaphragm or cervical or vault caps] with spermicidal foam or gel or film or
cream or suppository, or vasectomy) throughout the study and for up to 6 months
after the last dose of zimberelimab or quemliclustat
- Immunosuppressive doses of systemic medications, such as corticosteroids or absorbed
topical corticosteroids (doses > 10 mg/day prednisone or equivalent) must be
discontinued at least 2 weeks (14 days) before study treatment administration.
Physiologic doses of corticosteroids (=< 10 mg/day of prednisone or its equivalent)
or short pulses of corticosteroids (=< 3 days) may be permitted
- Prior surgery that required general anesthesia or other major surgery as defined by
the Investigator must be completed at least 4 weeks before study treatment
administration. Surgery requiring regional/epidural anesthesia must be completed at
least 72 hours before study treatment administration. Participants should have
recovered from the surgical procedure prior to the first dose being administered
Exclusion Criteria:
- 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
- Known pregnancy, nursing women or positive pregnancy test. Requirement for women of
child-bearing potential (WOCBP): Negative serum pregnancy test at screening and
prior to dosing on Cycle 1 Day 1, within 24 hours prior to the start of treatment
(minimum sensitivity 25 IU/L or equivalent units of HCG). WOCBP must also have a
negative serum or urine pregnancy test every 4 weeks, within 24 hours prior to the
start of treatment
- Any condition (concurrent disease, infection, or comorbidity) that interferes with
ability to participate in the study, causes undue risk, or complicates the
interpretation of safety data, in the opinion of the investigator
- History of trauma or major surgery within 28 days prior to the first dose of IP
- Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial
- Any active or documented history of autoimmune disease, including but not limited to
inflammatory bowel disease, celiac disease, Wegner syndrome, Hashimoto syndrome,
systemic lupus erythematosus, scleroderma, sarcoidosis, or autoimmune hepatitis,
within 3 years of the first dose of study treatment, except for the following:
- Type I diabetes mellitus, hypothyroidism only requiring hormone replacement,
skin disorders such as vitiligo, or alopecia not requiring systemic therapy, or
conditions not expected to recur in the absence of an external trigger
- Endocrinopathies where the participant is stable on hormone replacement therapy
- History of Hashimoto syndrome within 3 years of the first of study treatment
that resolved to hypothyroidism alone
- History of a syndrome that required systemic steroids or immunosuppressive
medications, except for vitiligo or resolved childhood asthma/atopy. Participants
with asthma who require intermittent use of bronchodilators (such as albuterol) will
not be excluded from this study
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Yonemoto,Lisa
Address:
City:
Los Angeles
Zip:
90095
Country:
United States
Status:
Recruiting
Contact:
Last name:
Lisa A. Yonemoto
Phone:
3105824069
Email:
LYonemoto@mednet.ucla.edu
Contact backup:
Last name:
Zev A. Wainberg, MD
Start date:
March 7, 2023
Completion date:
May 1, 2026
Lead sponsor:
Agency:
Jonsson Comprehensive Cancer Center
Agency class:
Other
Collaborator:
Agency:
Arcus Biosciences, Inc.
Agency class:
Industry
Source:
Jonsson Comprehensive Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05688215
