Perspectives in the treatment of pancreatic adenocarcinoma

Table 1 Controlled trials in adjuvant chemoradiotherapy for pancreatic ductal adenocarcinoma

Study name	No. of patients enrolled	Regimen	Survival rate	P value	Ref.
EORTC	207	5-FU + radiotherapy	34% (2 yr)	0.099	[72]
		Observation	26% (2 yr)
ESPAC-1	289	5-FU + radiotherapy	10% (5 yr)	-	[73]
		Observation or 5-FU only	20% (5 yr)
RTOG 9704	451	Gemcitabine + radiotherapy	18% (5 yr)	0.120	[147]
		5-FU + radiotherapy	22% (5 yr)

EORTC: European Organization for Research and Treatment of Cancer; ESPAC-1: European Study Group for Pancreatic Cancer 1; RTOG 9704: Radiation Therapy Oncology Group 9704; 5-FU: 5-fluoruracil.

Table 2 Controlled trials in adjuvant chemotherapy for pancreatic ductal adenocarcinoma

Study name	No. of patients enrolled	Regimen	Survival rate	P value	Ref.
CONKO-001	368	Gemcitabine	20.7% (5 yr)	0.01	[145]
		Observation	10.4% (5 yr)
ESPAC-3	1088	Gemcitabine	23.6 mo	0.39	[146]
		5-FU + Leucovorin	23.0 mo
JASPAC 01	385	Gemcitabine	53%	0.0001	[64]
		S-1	70%

CONKO-001: Charité Onkologie 001; ESPAC-3: European Study Group for Pancreatic Cancer 3; JASPAC 01: Japan Adjuvant Study Group of Pancreatic Cancer 01; 5-FU: 5-fluoruracil.

Table 3 Summary of major ongoing clinical trials evaluating immunotherapy approaches in patients with solid tumors including advanced or metastatic pancreatic adenocarcinoma

Study ID	Sponsor(s)	Therapeutic products	Phase	ClinicalTrials.gov Identifier
Monoclonal antibodies as checkpoint immunomodulators
CD-ON-MEDI4736-1108	MedImmune LLC	MEDI4736 (monoclonal antibody anti-B7 homolog1; PD-L1)	I/II	NCT01693562
GO27831	Genentech Inc.	MPDL3280A (human, Fc optimized monoclonal anti-PD-L1 antibody)	I	NCT01375842
3475-028	Merck Sharp and Dohme Corp	Pembrolizumab (humanized monoclonal anti-PD-1 antibody)	IB	NCT02054806
GP28328	Genentech, Inc.	MPDL3280A (human, Fc optimized monoclonal anti-PD-L1 antibody) plus bevacizumab (anti-VEGF antibody) and/or chemotherapy	I	NCT01633970
11-C-0100	Georgia Regents University Cancer Center	CT-011 (pidilizumab, humanized monoclonal antibody anti-PD-1) plus gemcitabine	II	NCT01313416
CA209-032	Bristol-Myers Squibb	Nivolumab (fully human monoclonal anti-PD-1 antibody) plus ipilimumab (anti-CTLA-4 monoclonal antibody)	I/II	NCT01928394
CA223-001	Bristol-Myers Squibb	Lirilumab (fully humanized monoclonal anti-KIR2DL1/2L3 antibody) plus nivolumab (anti-PD-1 antibody)	I	NCT01714739
NU 10I02	Northwestern University and Robert H. Lurie Cancer Center	Ipilimumab (anti-CTLA-4 monoclonal antibody) plus gemcitabine	I	NCT01473940
NCI-2013-00030	M.D. Anderson Cancer Center	Ipilimumab (anti-CTLA-4 monoclonal antibody) plus imatinib	I	NCT01738139
CA224-020	Bristol-Myers Squibb	BMS-986016 (anti-LAG-3 antibody) with or without nivolumab (anti-PD-1 antibody)	I	NCT01968109
CA186-011	Bristol-Myers Squibb	Urelumab (BMS-663513, humanized agonistic monoclonal anti-4-1BB/CD137)	I	NCT01471210
B1641001	Pfizer	PF-05082566 (4-1BB humanized agonist monoclonal antibody) plus rituximab (anti-CD20)	I	NCT01307267
Monoclonal antibodies as signaling pathway inhibitors
59R5-002	OncoMed Pharmaceuticals, Inc.	OMP-59R5 (anti-Notch2/3) plus chemotherapy	I/II	NCT01647828
52M51-002	OncoMed Pharmaceuticals, Inc. and GlaxoSmithKline	OMP-52M51 (anti-Notch 1 monoclonal antibody)	I	NCT01778439
MORAb-066-001	Morphotek and SCRI Development Innovations, LLC	MORAb-066: anti-human TF (tissue factor, CD142) monoclonal antibody	I	NCT01761240
NCI-2012-01702	Morphotek and National Cancer Institute (NCI)	Ontuxizumab (MORAb-004): monoclonal antibody anti-endosialin/TEM1 (CD248)	I	NCT01748721
R1400-ST-1113	Regeneron Pharmaceuticals	REGN1400 (anti-ErbB3) with or without erlotinib or cetuximab	I	NCT01727869
MM-151-01-01-01	Merrimack Pharmaceuticals	MM-151 [oligoclonal antibody composed of three fully human monoclonal antibodies anti-EGFR (ErbB1)] alone and with irinotecan	I	NCT01520389
M12-375	AbbVie (prior sponsor, Abbott)	ABT-700 [monoclonal antibody anti-c-Met human growth factor receptor (HGFR) as monotherapy, or with chemotherapy (FOLFIR/cetuximab) or with erlotinib	I	NCT01472016
UPCC-04206	University of Pennsylvania and NCI	Gemcitabine, oxaliplatin and bevacizumab followed by 5-fluorouracil, oxaliplatin, bevacizumab and radiotherapy in patients with locally advanced pancreatic cancer	II	NCT00602602
Monoclonal antibodies as cytotoxicity inducers
Neogenix 0901	Precision Biologics, Inc	Ensituximab (NPC-1C/NEO-102) (anti-MUC5AC-related antigen)	I/II	NCT01040000
CEP-37250/KHK2804-001	Kyowa Hakko Kirin Pharma, Inc.	CEP-37250/KHK2804 (monoclonal antibody targeting glycolipids on the surface of tumor cells)	I	NCT01447732
IMMU-107-04	Immunomedics, Inc.	IMMU-107: radioimmunoconjugate of the humanized monoclonal antibody HuPAM4 (anti-MUC1), plus a chelating agent (DOTA) and radiolabeled with Yttrium Y90	III	NCT01956812
Therapeutic vaccines
NLG0505	NewLink Genetics Corporation	Algenpantucel-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.	III	NCT01836432
11-C-0148	NCI	Epigenetically modified autologous tumor cells with ISCOMATRIX Adjuvant plus chemotherapy	I	NCT01341496
ADU-CL-04	Aduro BioTech, Inc.	GVAX (allogeneic GM-CSF transfected pancreatic tumor vaccine) plus CRS-207 (attenuated L. monocytogenes expressing mesothelin)	II	NCT02004262
J13108	Sidney Kimmel CCC	GVAX (allogeneic GM-CSF transfected pancreatic tumor vaccine) plus ipilimumab compared with FOLFIRINOX	II	NCT01896869
JHOC-J0810	Sidney Kimmel CCC and NCI	GVAX (allogeneic GM-CSF transfected pancreatic tumor vaccine) plus cyclophosphamide	NP	NCT00727441
NCI-2012-01548	Jonsson Comprehensive Cancer Center	NY-ESO-1 (cancer-testis antigen) reactive TCR retroviral vector transduced autologous PBL	II	NCT01697527
NWBio 050012	Northwest Biotherapeutics	DCVax-Direct (autologous activated dendritic cells)	I/II	NCT01882946
ONT-10-001	Oncothyreon Inc.	ONT-10 (liposomal MUC1 cancer vaccine)	I	NCT01556789
J1179	Sidney Kimmel Comprehensive Cancer Center	PANC 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 chemotherapy	NP	NCT01595321
101778	Medical University of South Carolina	Poly-ICLC (ligand for toll like receptor) and dendritic cells, plus standard chemotherapy	0	NCT01677962
I 191511	Roswell Park Cancer Institute	DEC-205-NY-ESO-1 (cancer-testis antigen) fusion protein vaccine	I	NCT01522820
Adoptive T cell therapy
UPCC 08212	Abramson Cancer Center of the University of Pennsylvania	Autologous T cells transfected with chimeric anti-mesothelin immunoreceptor SS1, plus chemotherapy	I	NCT01897415
UPCC 31213	Abramson Cancer Center of the University of Pennsylvania	CART-meso (autologous T cells lentivirally transduced with chimeric anti-mesothelin immunoreceptor SS1 fused to the 4-1BB and CD3ζ signaling domains)	I	NCT02159716
12-C-0111	NCI	Anti-mesothelin CAR plus chemotherapy and aldesleukin	I/II	NCT01583686
10-C-0166	NCI	Young tumor infiltrating lymphocytes (TILs), plus chemotherapy and aldesleukin	II	NCT01174121
13-C-0214	NCI	Anti-NY ESO-1 mTCR PBL (autologous white blood cells genetically modified with a retrovirus expressing the gene for anti-ESO-1), plus chemotherapy and aldesleukin	II	NCT01967823
14-C-0052	NCI	Anti-MAGE-A3-DP4 TCR (autologous T cells genetically modified with a retrovirus expressing the gene for anti-MAGE-A3-DP0401/0402), plus chemotherapy and aldesleukin	I/II	NCT02111850
11-C-0013	NCI	Anti-VEGFR2 CAR: Autologous CD8+ T cells genetically modified with a retrovirus expressing the gene for anti-VEGFR2, plus chemotherapy and aldesleukin	I/II	NCT01218867
RWH 111-32	Roger Williams Medical Center	EGFRBi-armed autologous activated T cells, loaded with a bispecific antibody produced by heteroconjugation of anti-CD3 and anti-EGFR monoclonal antibodies	I	NCT01081808
Adjuvant immunotherapies and cytokines
NCI-2011-03565	Roswell Park Cancer Institute, NCI and Cleveland BioLabs Inc.	Entolimod (CBLB502, recombinant Toll-like receptor 5 agonist)	I	NCT01527136
AM0010-001	ARMO BioSciences	AM0010 (pegylated recombinant human interleukin-10) in combination with chemotherapy	I	NCT02009449