| Eligibility |
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
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