Review
Copyright ©The Author(s) 2015.
World J Gastroenterol. Aug 21, 2015; 21(31): 9297-9316
Published online Aug 21, 2015. doi: 10.3748/wjg.v21.i31.9297
Table 1 Controlled trials in adjuvant chemoradiotherapy for pancreatic ductal adenocarcinoma
Study nameNo. of patients enrolledRegimenSurvival rateP valueRef.
EORTC2075-FU + radiotherapy34% (2 yr)0.099[72]
Observation26% (2 yr)
ESPAC-12895-FU + radiotherapy10% (5 yr)-[73]
Observation or 5-FU only20% (5 yr)
RTOG 9704451Gemcitabine + radiotherapy18% (5 yr)0.120[147]
5-FU + radiotherapy22% (5 yr)
Table 2 Controlled trials in adjuvant chemotherapy for pancreatic ductal adenocarcinoma
Study nameNo. of patients enrolledRegimenSurvival rateP valueRef.
CONKO-001368Gemcitabine20.7% (5 yr)0.01[145]
Observation10.4% (5 yr)
ESPAC-31088Gemcitabine23.6 mo0.39[146]
5-FU + Leucovorin23.0 mo
JASPAC 01385Gemcitabine53%0.0001[64]
S-170%
Table 3 Summary of major ongoing clinical trials evaluating immunotherapy approaches in patients with solid tumors including advanced or metastatic pancreatic adenocarcinoma
Study IDSponsor(s)Therapeutic productsPhaseClinicalTrials.gov Identifier
Monoclonal antibodies as checkpoint immunomodulators
CD-ON-MEDI4736-1108MedImmune LLCMEDI4736 (monoclonal antibody anti-B7 homolog1; PD-L1)I/IINCT01693562
GO27831Genentech Inc.MPDL3280A (human, Fc optimized monoclonal anti-PD-L1 antibody)INCT01375842
3475-028Merck Sharp and Dohme CorpPembrolizumab (humanized monoclonal anti-PD-1 antibody)IBNCT02054806
GP28328Genentech, Inc.MPDL3280A (human, Fc optimized monoclonal anti-PD-L1 antibody) plus bevacizumab (anti-VEGF antibody) and/or chemotherapyINCT01633970
11-C-0100Georgia Regents University Cancer CenterCT-011 (pidilizumab, humanized monoclonal antibody anti-PD-1) plus gemcitabineIINCT01313416
CA209-032Bristol-Myers SquibbNivolumab (fully human monoclonal anti-PD-1 antibody) plus ipilimumab (anti-CTLA-4 monoclonal antibody)I/IINCT01928394
CA223-001Bristol-Myers SquibbLirilumab (fully humanized monoclonal anti-KIR2DL1/2L3 antibody) plus nivolumab (anti-PD-1 antibody)INCT01714739
NU 10I02Northwestern University and Robert H. Lurie Cancer CenterIpilimumab (anti-CTLA-4 monoclonal antibody) plus gemcitabineINCT01473940
NCI-2013-00030M.D. Anderson Cancer CenterIpilimumab (anti-CTLA-4 monoclonal antibody) plus imatinibINCT01738139
CA224-020Bristol-Myers SquibbBMS-986016 (anti-LAG-3 antibody) with or without nivolumab (anti-PD-1 antibody)INCT01968109
CA186-011Bristol-Myers SquibbUrelumab (BMS-663513, humanized agonistic monoclonal anti-4-1BB/CD137)INCT01471210
B1641001PfizerPF-05082566 (4-1BB humanized agonist monoclonal antibody) plus rituximab (anti-CD20)INCT01307267
Monoclonal antibodies as signaling pathway inhibitors
59R5-002OncoMed Pharmaceuticals, Inc.OMP-59R5 (anti-Notch2/3) plus chemotherapyI/IINCT01647828
52M51-002OncoMed Pharmaceuticals, Inc. and GlaxoSmithKlineOMP-52M51 (anti-Notch 1 monoclonal antibody)INCT01778439
MORAb-066-001Morphotek and SCRI Development Innovations, LLCMORAb-066: anti-human TF (tissue factor, CD142) monoclonal antibodyINCT01761240
NCI-2012-01702Morphotek and National Cancer Institute (NCI)Ontuxizumab (MORAb-004): monoclonal antibody anti-endosialin/TEM1 (CD248)INCT01748721
R1400-ST-1113Regeneron PharmaceuticalsREGN1400 (anti-ErbB3) with or without erlotinib or cetuximabINCT01727869
MM-151-01-01-01Merrimack PharmaceuticalsMM-151 [oligoclonal antibody composed of three fully human monoclonal antibodies anti-EGFR (ErbB1)] alone and with irinotecanINCT01520389
M12-375AbbVie (prior sponsor, Abbott)ABT-700 [monoclonal antibody anti-c-Met human growth factor receptor (HGFR) as monotherapy, or with chemotherapy (FOLFIR/cetuximab) or with erlotinibINCT01472016
UPCC-04206University of Pennsylvania and NCIGemcitabine, oxaliplatin and bevacizumab followed by 5-fluorouracil, oxaliplatin, bevacizumab and radiotherapy in patients with locally advanced pancreatic cancerIINCT00602602
Monoclonal antibodies as cytotoxicity inducers
Neogenix 0901Precision Biologics, IncEnsituximab (NPC-1C/NEO-102) (anti-MUC5AC-related antigen)I/IINCT01040000
CEP-37250/KHK2804-001Kyowa Hakko Kirin Pharma, Inc.CEP-37250/KHK2804 (monoclonal antibody targeting glycolipids on the surface of tumor cells)INCT01447732
IMMU-107-04Immunomedics, Inc.IMMU-107: radioimmunoconjugate of the humanized monoclonal antibody HuPAM4 (anti-MUC1), plus a chelating agent (DOTA) and radiolabeled with Yttrium Y90IIINCT01956812
Therapeutic vaccines
NLG0505NewLink Genetics CorporationAlgenpantucel-L Immunotherapy: 2 pancreatic cancer cell lines (HAPa-1 and HAPa-2) expressing murine alpha-gal carbohydrates on cell surface molecules, in combination with standard therapy, compared with standard therapy.IIINCT01836432
11-C-0148NCIEpigenetically modified autologous tumor cells with ISCOMATRIX Adjuvant plus chemotherapyINCT01341496
ADU-CL-04Aduro BioTech, Inc.GVAX (allogeneic GM-CSF transfected pancreatic tumor vaccine) plus CRS-207 (attenuated L. monocytogenes expressing mesothelin)IINCT02004262
J13108Sidney Kimmel CCCGVAX (allogeneic GM-CSF transfected pancreatic tumor vaccine) plus ipilimumab compared with FOLFIRINOXIINCT01896869
JHOC-J0810Sidney Kimmel CCC and NCIGVAX (allogeneic GM-CSF transfected pancreatic tumor vaccine) plus cyclophosphamideNPNCT00727441
NCI-2012-01548Jonsson Comprehensive Cancer CenterNY-ESO-1 (cancer-testis antigen) reactive TCR retroviral vector transduced autologous PBLIINCT01697527
NWBio 050012Northwest BiotherapeuticsDCVax-Direct (autologous activated dendritic cells)I/IINCT01882946
ONT-10-001Oncothyreon Inc.ONT-10 (liposomal MUC1 cancer vaccine)INCT01556789
J1179Sidney Kimmel Comprehensive Cancer CenterPANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1/GM-Neo vaccine, plus cyclophosphamide followed by SBRT (fractionated stereotactic body radiation therapy) and FOLFIRINOX chemotherapyNPNCT01595321
101778Medical University of South CarolinaPoly-ICLC (ligand for toll like receptor) and dendritic cells, plus standard chemotherapy0NCT01677962
I 191511Roswell Park Cancer InstituteDEC-205-NY-ESO-1 (cancer-testis antigen) fusion protein vaccineINCT01522820
Adoptive T cell therapy
UPCC 08212Abramson Cancer Center of the University of PennsylvaniaAutologous T cells transfected with chimeric anti-mesothelin immunoreceptor SS1, plus chemotherapyINCT01897415
UPCC 31213Abramson Cancer Center of the University of PennsylvaniaCART-meso (autologous T cells lentivirally transduced with chimeric anti-mesothelin immunoreceptor SS1 fused to the 4-1BB and CD3ζ signaling domains)INCT02159716
12-C-0111NCIAnti-mesothelin CAR plus chemotherapy and aldesleukinI/IINCT01583686
10-C-0166NCIYoung tumor infiltrating lymphocytes (TILs), plus chemotherapy and aldesleukinIINCT01174121
13-C-0214NCIAnti-NY ESO-1 mTCR PBL (autologous white blood cells genetically modified with a retrovirus expressing the gene for anti-ESO-1), plus chemotherapy and aldesleukinIINCT01967823
14-C-0052NCIAnti-MAGE-A3-DP4 TCR (autologous T cells genetically modified with a retrovirus expressing the gene for anti-MAGE-A3-DP0401/0402), plus chemotherapy and aldesleukinI/IINCT02111850
11-C-0013NCIAnti-VEGFR2 CAR: Autologous CD8+ T cells genetically modified with a retrovirus expressing the gene for anti-VEGFR2, plus chemotherapy and aldesleukinI/IINCT01218867
RWH 111-32Roger Williams Medical CenterEGFRBi-armed autologous activated T cells, loaded with a bispecific antibody produced by heteroconjugation of anti-CD3 and anti-EGFR monoclonal antibodiesINCT01081808
Adjuvant immunotherapies and cytokines
NCI-2011-03565Roswell Park Cancer Institute, NCI and Cleveland BioLabs Inc.Entolimod (CBLB502, recombinant Toll-like receptor 5 agonist)INCT01527136
AM0010-001ARMO BioSciencesAM0010 (pegylated recombinant human interleukin-10) in combination with chemotherapyINCT02009449