A randomized pilot phase I study of modified carcinoembryonic antigen (CEA) peptide (CAP1-6D)/montanide/GM-CSF-vaccine in patients with pancreatic adenocarcinoma.
BACKGROUND
CEA is expressed in >90% of pancreatic cancers (PC) and may be an appropriate immunotherapy target. CEA is poorly immunogenic due to immune tolerance; CAP1-6D, an altered peptide ligand can help bypass tolerance. We conducted a pilot randomized phase I trial in PC patients to determine the peptide dose required to induce an optimal CD8(+) T cell response.


METHODS
Patients with a PS 0-1, HLA-A2+ and CEA-expressing, previously-treated PC were randomized to receive 10 μg (arm A), 100 μg (arm B) or 1000 μg (arm C) of CEA peptide emulsified in Montanide and GM-CSF, given every 2 weeks until disease progression.


RESULTS
Sixty-six patients were screened and 19 enrolled of whom 14 received at least 3 doses of the vaccine and thus evaluated for the primary immunologic endpoint. A median of 4 cycles (range 1-81) was delivered. Median and mean peak IFN-γ T cell response by ELISPOT (spots per 10(4) CD8(+) cells, Arm A/B/C) was 11/52/271 (A vs. C, p = 0.028) for medians and 37/148/248 (A vs. C, p = 0.032) for means. T cell responses developed or increased in 20%/60%/100% of pts in Arms A/B/C. Seven of the 19 patients remain alive at a minimum 32 months from trial initiation, including three with unresectable disease.


CONCLUSIONS
The T cell response in this randomized phase I trial was dose-dependent with the 1 mg CEA peptide dose eliciting the most robust T cell responses. A signal of clinical benefit was observed and no significant toxicity was noted. Further evaluation of 1 mg CEA peptide with stronger adjuvants, and/or combined with agents to overcome immune inhibitory pathways, may be warranted in PC pts.


BACKGROUND
ClinicalTrials.gov NCT00203892.
Section of Hematology/Oncology, University of Chicago, Chicago, IL, USA.|University of Chicago Cancer Research Center, Chicago, IL, USA.
Daniel M
DM
Geynisman
University of Chicago Cancer Research Center, Chicago, IL, USA.
Yuanyuan
Y
Zha
Department of Health Studies, University of Chicago, Chicago, IL, USA.
Rangesh
R
Kunnavakkam
Section of Hematology/Oncology, University of Chicago, Chicago, IL, USA.
Mebea
M
Aklilu
Section of Hematology/Oncology, University of Chicago, Chicago, IL, USA.|University of Chicago Cancer Research Center, Chicago, IL, USA.
Daniel Vt
DV
Catenacci
Section of Hematology/Oncology, University of Chicago, Chicago, IL, USA.|University of Chicago Cancer Research Center, Chicago, IL, USA.
Blase N
BN
Polite
Section of Hematology/Oncology, University of Chicago, Chicago, IL, USA.|University of Chicago Cancer Research Center, Chicago, IL, USA.
Cara
C
Rosenbaum
Section of Hematology/Oncology, University of Chicago, Chicago, IL, USA.
Azadeh
A
Namakydoust
Department of Health Studies, University of Chicago, Chicago, IL, USA.
Theodore
T
Karrison
Section of Hematology/Oncology, University of Chicago, Chicago, IL, USA.|University of Chicago Cancer Research Center, Chicago, IL, USA.
Thomas F
TF
Gajewski
Section of Hematology/Oncology, University of Chicago, Chicago, IL, USA.|University of Chicago Cancer Research Center, Chicago, IL, USA.|Section of Hematology/Oncology, Department of Medicine, University of Chicago, 5841 South Maryland Avenue, MC 2115, Chicago, IL 60637, USA.
Hedy L
HL
Kindler
CEA; Immunization; Pancreatic Cancer; Vaccine