This is a Phase 3, randomized, double-blind trial to evaluate the efficacy and safety of
neoadjuvant treatment with pamrevlumab or placebo in combination with either gemcitabine plus
nab-paclitaxel (G/NP) or FOLFIRINOX in the treatment of locally advanced, unresectable
pancreatic cancer subjects.
Subjects will be randomized in a 1:1 ratio to one of the two study treatment arms;
pamrevlumab with either G/NP or FOLFIRINOX, placebo with G/NP or FOLFIRINOX.
Each subject may receive up to six cycles of treatment (each treatment cycle is 28 days).
Tumor tissue will be collected during resection to determine surgical outcome and for
biomarker analysis. Tumor response will be evaluated by changes in CT scan, FDG-PET, CA 19-9,
and NCCN® guidelines.
All subjects randomized will have a safety follow-up visit approximately 28 days after the
last dose of study treatment and a final safety follow-up phone call at approximately 60 days
after the last dose.
Subjects who complete 6 cycles of treatment will be evaluated for surgical exploration for
possible R0 or R1 resection. Surgery will occur at least 4 weeks after the last dose
(allowing for a wash-out period from treatment) and only after receipt of the recommendation
from the central review board with regards to surgical eligibility. Surgery will occur no
longer than 8 weeks after the last dose. Subjects who undergo surgery will be evaluated for
surgical complications for at least an additional 90 days following discharge from surgery.
Subjects who are ineligible for surgical exploration (i.e. subjects who did not complete 6
cycles of treatment or do not meet any of the protocol defined criteria or had a
contraindication to surgery) will continue in the Follow-up period and receive treatment as
per standard of care (SOC) for each institution.
All subjects will be followed for disease progression (if not previously detected) or
recurrence following resection (local progression or metastatic disease). Subjects will also
be followed for any additional anti-cancer therapy received for their pancreatic cancer. All
subjects will be followed for survival (until death) or until the last subject to complete
treatment reaches 18 months post-treatment.
Inclusion Criteria:
1. Understand and sign informed consent; be willing to comply with study procedures,
including surgery
2. Age ≥ 18 years
3. Be a male, or non-pregnant and non-lactating female
4. Negative serum B-hCG pregnancy test at screening for women of childbearing potential
5. Male subjects with partners of childbearing potential and female subjects of
childbearing potential are required to use highly effective contraception methods
during the conduct of the study and for 6 months after the last dose of study drug
6. Histologically or cytologically proven diagnosis of pancreatic ductal adenocarcinoma
(PDAC)
7. Locally advanced pancreatic cancer considered unresectable according to NCCN
Guidelines® Version 2.2018 as determined by central imaging
8. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors RECIST
1.1 criteria as determined by central imaging
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
10. Adequate liver function: aspartate aminotransferase (AST) and alanine aminotransferase
(ALT) <2.5 x upper limit of normal (ULN), alkaline phosphatase <2.5 x ULN, and
bilirubin ≤1.5 x ULN or in subjects with biliary stenting ≤2.0 x ULN
11. Adequate bone marrow function: platelets >100,000 cells/mm3, hemoglobin >9.0 g/dl and
absolute neutrophil count (ANC) >1,500 cells/mm3
12. Adequate renal function: creatinine < 1.5 x ULN, creatinine clearance ≥ 30 mL/min
13. Less than grade 2 pre-existing peripheral neuropathy (per CTCAE)
Exclusion Criteria:
1. Prior chemotherapy or radiation for pancreatic cancer
2. Previous (within the past 3 years) or concurrent malignancy diagnosis except
non-melanoma skin cancer and in situ carcinomas (excluding in situ breast cancer)
3. Major surgery within 4 weeks prior to signing informed consent form. Biliary stents
are permitted.
4. History of allergy or hypersensitivity to human, humanized or chimeric monoclonal
antibodies
5. History of allergy or hypersensitivity to any of the chemotherapy agents being
prescribed or their excipients
6. Any medical or surgical condition that may place the subject at increased risk while
on study
7. Any condition potentially decreasing compliance to study procedures
8. Exposure to another investigational drug within 28 days of first dosing visit, or 5
half-lives of the investigational drug (whichever is longer)
9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
systemic infections, symptomatic congestive heart failure, unstable angina pectoris,
clinically significant cardiac arrhythmia, or psychiatric illness/social situations
that would limit compliance with study requirements
10. Documented history of drug or alcohol abuse within 6 months of signing informed
consent
11. Any medical condition that, in the opinion of the investigator, may pose a safety risk
to a subject in this trial, may confound the assessment of safety and efficacy, or may
interfere with study participation
12. Subjects with a history of; interstitial pulmonary disease, HCV, HBV or HIV infection
13. Subjects who have been administered a live vaccine within four weeks prior to the
first administration of therapy
14. Subjects who cannot stop chronic medications that inhibit or induce CYP2C8 or CYP3A4
15. Subjects with poorly controlled comorbid conditions, including; congestive heart
failure (CHF), chronic obstructive pulmonary disease (COPD), uncontrolled diabetes
mellitus (DM) or neurologic disorders (not acutely related to pancreatic cancer) or
limited function
