Supplementary Table 1. Active immunotherapies in phase II development
Adjuvants/
immune
modulators
Study population
PSA
GM-CSF + costimulators
Metastatic, castrationresistant prostate cancer
125
Viral vector
(adenovirus)
PSA
Vector
Recurrent/hormonerefractory prostate cancer
44
mRNA:
CV9103/9104,
CureVac®
PSA + PSCA
+
PSMA +
STEAP1
mRNA
Metastatic, castrationresistant prostate cancer
38
HER2
GM-CSF
High-risk breast cancer, in
remission after standard
treatment
182
HER2
GM-CSF
High-risk breast cancer, in
remission after standard
treatment
172
EGFR
Montanide
ISA51 + CYC
Stage IIIB/IV NSCLC,
after chemotherapy
80
Telomerase
GM-CSF
Unresectable stage III
NSCLC; after
chemoradiotherapy
23
Type of
immunotherapy
Antigens
Prostate cancer
Viral vector (vaccinia/
fowlpox prime/boost):
Prostvac®-VF
Breast cancer
Peptide:
nelipepimut-S (E75),
NeuVax™
Peptide:
GP2
Lung cancer
Peptide:
CIMAvax EGF
Peptide:
GV1001
Patients(N)
Efficacy results*
Citation
Clinical
OS: 25.1 mo vs. 16.6 mo (HR 0.56; P=0.0061)
PFS: 3.8 mo vs. 3.7 mo (HR 0.88; P=0.60)
Immunologic
No detectable antibody responses to PSA
Clinical
Increase in PSA doubling time in 64% of patients
Immunologic
T cell response: 100% (recurrent disease) and 67% (hormone-refractory
disease) of patients
Clinical
Prolonged stabilization of PSA levels for individual patients
Immunologic
T cell response: 79% of patients, 58% with multiepitope responses
Kantoff, P. W. et al. J. Clin.
Oncol. 28, 1099-1105 (2010).
NCT01322490
Clinical
2-yr DFS:
Overall: 94.3% vs. 86.8% (P=0.08)
Low HER2-expressing tumours: 94.0% vs. 79.4% (P=0.04)
High HER2-expressing tumours: 90.3% vs. 83.3% (P=0.44)
Clinical
Recurrence rate: 4.3% vs. 11.6% (P=0.41)
Immunologic
DTH: 21.5 vs. 6.0 mm (P<0.01)
Mittendorf, E. A. et al. Cancer.
118, 2594-2602 (2012).
NCT01479244
Clinical
OS:
Overall (vaccine vs. control): 6.5 mo vs. 5.3 mo (P=0.098)
Good vs. poor immune responders: 11.7 mo vs. 3.6 mo (P=0.002)
Good immune responders vs. control: 11.7 mo vs. 5.3 mo (P=0.0024)
Immunologic
Good antibody response in 51% of patients
Clinical
OS: 28.8 mo
PFS:
Overall: 11.7 mo;
Immune responders vs. non-responders: 12.2 mo vs. 6.0 mo (P=0.20)
Immunologic
T cell response: 16/23 patients (69.6%)
Neninger Vinageras E. et al. J
Clin Oncol. 26, 1452-1458
(2008). NCT01444118
Lubaroff, D. M. et al. Cancer
Res. 72, Abstr 2692 (2012).
Kübler, H. et al. J. Clin. Oncol.
29 suppl., Abstr 4535 (2011).
Trappey, F. et al. J. Clin.
Oncol. 31, Abstr 3005 (2013).
Brunsvig, P. F. et al. Clin.
Cancer Res. 17, 6847-6857
(2011). NCT01579188
Viral vector (vaccinia):
TG4010
MUC1
Adjuvants/
immune
modulators
Vector + IL-2
Allogeneic tumour cell:
belagenpumatucel-L,
Lucanix™
Allogeneic tumour cell:
tergenpumatucel-L,
HyperAcute® Lung
Tumour cell
Anti-idiotype:
racotumomab
Type of
immunotherapy
Antigens
Study population
Patients(N)
Stage IV NSCLC, with
chemotherapy
148
Anti-TGF-β
Stage II–IV NSCLC; after
front-line chemotherapy
75
Tumour cell
αGT
Stage IIIB/IV NSCLC;
progressive or relapsed
after chemotherapy
28
Idiotype
Alum
Stage IIIB/IV NSCLC;
after primary treatment
176
survivin
Montanide
ISA51 + CYC
Metastatic, treatmentrefractory stage IV
melanoma
61
Peptide
gp100 +
MART-1 +
tyrosinase
GM-CSF +
Montanide
ISA51
Metastatic melanoma
22
Dendritic cell
gp100 +
MAGE-A1,
A2, A3 +
MART-1 +
tyrosinase
KLH
Metastatic melanoma
24
Dendritic cell
gp100 +
tyrosinase
(MHC-I/II)
KLH
Stage III/IV melanoma
33
Dendritic cell
survivin +
telomerase +
p53
IL-2 + CYC
+celecoxib
Metastatic melanoma
28
Melanoma
Peptide
Efficacy results*
Citation
Clinical
6-mo PFS: 43.2% vs. 35.1% (P=0.307)
OS: 10.7 mo vs. 10.3 mo (P=0.59)
TTP: 5.9 mo vs. 5.2 mo (P=0.070)
ORR: 41.9% vs. 28.4% (P=0.082)
Outcomes worse than control in subset of patients with high levels of activated
natural killer cells.
Immunologic
No significant differences between study arms in cellular responses to MUC1
Clinical
OS: 14.4 mo; longer survival with higher (19.1 mo) vs. low (8.3 mo; P=0.0186)
dose immunization
Clinical
OS:
Overall: 11.3 mo
IFN responders vs. non-responders: 21.9 mo vs. 5.5 mo (P<0.001)
Immunologic
Increased IFN responses in 61% of patients
Clinical
OS: 8.3 mo vs. 6.3 mo (P=0.02)
Quoix, E. et al. Lancet Oncol.
12, 1125-1133 (2011).
NCT01383148
Clinical
OS:
Overall: 9.1 mo
Immune responders vs. non-responders: 19.6 mo vs. 8.6 mo; P=0.0077)
PFS:
Overall: 2.8 mo
Immunologic
T cell responses in 13/41 (32%) patients
Clinical
OS: 13.4 mo
PFS: 1.9 mo
Immunologic
T cell responses in 9/20 (45%) patients
Clinical
OS:
Overall: 13.6 mo (vs. 7.3 mo matched controls)
Immune responders vs. non-responders: 21.9 mo vs. 8.1 mo
Immunologic
T cell responses in 18/24 (75%) patients; multiepitope responses in 13/24
(54%) patients
Clinical
OS: 15.0 mo (vs. 8.3 mo with matched controls; P=0.089)
PFS: 5.0 (vs. 2.8 mo with matched controls; P=0.0089)
Immunologic
T cell responses in 5/29 (17%) patients
Clinical
OS: 9.4 mo
Immunologic
Antigen-specific responses in 9/15 (60%) patients
Becker, J. C. et al. Cancer
Immunol. Immunother. 61,
2091-2103 (2012).
Nemunaitis, J. et al. J. Clin.
Oncol. 24, 4721-4730 (2006).
NCT00676507
Morris, J. C. et al. J. Clin.
Oncol. 30 suppl, Abstr 2571
(2012). NCT01774578
Macías, A. et al. Ann. Oncol.
23 suppl 9, Abstr 1238PD
(2012). NCT014604722
Tarhini, A. A. et al. J.
Immunother. 35, 359-366
(2012).
Oshita, C. et al. Oncol. Rep.
28, 1131-1138 (2012).
Aarntzen, E. H. et al. Cancer
Res. 73, 19-29 (2013).
Ellebaek, E. et al. Cancer
Immunol. Immunother. 61,
1791-1804 (2012).
Type of
immunotherapy
Antigens
Autologous tumour
cell:
MVax
Haptenmodified
tumour cells
Allogeneic tumour cell
Shed-antigens
Allogeneic tumour cell
Viral vector (vaccinia/
fowlpox prime/boost):
Prostvac®-VF
Pancreatic cancer
Peptide
Allogeneic tumour cell:
algenputacel-L
HyperAcute® Pancreas
Colorectal cancer
Viral vector
(adenovirus)
Dendritic cell
Modified with CEA +
MUC1-encoding
poxvector (PANVAC)
Renal cell carcinoma
Peptide:
IMA901
Adjuvants/
immune
modulators
BCG + IL2 +
CYC
Study population
Patients(N)
Efficacy results*
Citation
Clinical
OS:
With vs. without DTH to unmodified tumour cells: 16.5 vs 8.4 mo
(P=0.023)
Immunologic
DTH to unmodified tumour cells in 42% of patients
Clinical
OS: 45.6 mo vs.32.4 mo (P=NS)
Recurrence-free survival: 19.2 mo vs. 7.2 mo (P=0.03)
–
Berd, D. et al. Int. J. Cancer.
94, 531-539 (2001).
NCT00477906
25
Clinical
OS:
Overall: 48 mo
Immune responders vs. non responders: 82 mo vs. 15 mo (P=0.007)
PFS:
Overall: 9 mo
Immune responders vs. non-responders: 9 mo vs. 7 mo (P=0.16)
Immunologic
CD8+ T cell responses in 22/25 (88%) patients
Odunsi, K. et al. Proc. Natl.
Acad. Sci. USA. 109, 57975802 (2012).
Clinical
OS
Immune responders vs. non-responders: 4.8 mo vs. 2.0 mo (P=0.0002)
Immunologic
T cell responses in 17/43 (40%) patients
Clinical
1, 2 and 3-yr survival of 86%, 51% and 42%, respectively
Gjertsen, M. K. et al. Int. J.
Cancer. 92, 441-450 (2001).
Clinical
1-yr survival of 48%
Immunologic
T cell responses in 15/32 (47%) patients
Clinical
2-yr survival
DC modified with PANVAC vs. PANVAC alone: 47% vs. 55%; P=0.48).
Death
2/37 with DC-PANVAC vs. 5/37 with PANVAC alone
Morse, M. A. et al. Cancer
Immunol. Immunother. 62,
1293-1301 (2013).
Clinical
OS:
IMA901 + CYC vs. IMA alone: 23.5 mo vs. 14.8 mo (P=0.09)
Improved survival in patients with multiepitope responses (P=0.023)
Immunologic
T cell responses in 20/27 (74%) patients; multiepitope responses in 8/27
(30%) patients
Walter, S. et al. Nat. Med. 18,
1254-1261 (2012).
NCT01265901
Metastatic melanoma
97
Alum
Stage IIB/C or III
melanoma; post-surgery
38
Tumour cell
BCG + GM-CSF
≈108
NY-ESO-1
Vector
Stage IIB/C or III
melanoma; post-surgery
Stage III/IV melanoma
ras peptides
GM-CSF
Advanced/surgically
resected pancreatic
cancer
48
Tumour cell
α-GT
Surgically resected
pancreatic cancer, with
chemoradiotherapy
70
CEA
Vector
Metastatic colorectal
cancer
32
CEA +
MUC1/GMCSF
PLIN2 +
APOL1 +
CCND1 +
GUCY1A3 +
PRUNE2 +
MET + MUC1
+ RGS5 +
MMP7 +
HBcAg
Resected metastatic
colorectal cancer; after
resection (N=74)
GM-CSF ± CYC
Metastatic RCC
68
Bystryn, J. C. et al. Clin.
Cancer Res. 7, 1882-1887
(2001). NCT01546571
NCT01729663
Hardacre, J. M. et al. J.
Gastrointest. Surg. 17, 94-100
(2013). NCT01836432,
NCT01072981
Morse, M. A. et al. Ann. Surg.
258, 879-886 (2013).
Type of
immunotherapy
Antigens
Dendritic cell:
AGS-003
Tumour cell
RNA
Adjuvants/
immune
modulators
CD40L
Study population
Patients(N)
Efficacy results*
Citation
Metastatic RCC
21
Clinical
OS: 30.2 mo
PFS: 11.2 mo
Amin, A. et al. J. Clin. Oncol.
31 suppl, Abstr 357 (2013).
NCT01582672
19
Clinical
PFS: 1.6 mo (patients with AML and prior chemotherapy)
Objective response in 10/17 patients with AML, and stable disease after initial
progression in a further 4 patients
Immunologic
T cell responses in 8/18 (44%) patients
–
Keilholz, U. et al. Blood. 113,
6541-6548 (2009).
34
Clinical
Reduction in slope of paraprotein concentration in 13/29 patients
Immunologic
T cell responses in 15/32 (47%) of patients
Rossmann, E. et al. American
Society of Hematology Annual
Meeting. Abstr 2927 (2011).
10
Clinical
Normalization of WT1 mRNA levels in 5/10 patients, including 2 patients
converted from partial to full remission. Three long-term (≥3 yr) clinical
responders. Clinical responses correlated with innate and adaptive immune
responses
Van Tendeloo, V. F. et al.
Proc. Natl. Acad. Sci. USA.
107, 13824-13829 (2010).
Haematologic malignancies
Peptide
WT1
GM-CSF + KLH
Acute myeloid leukaemia
(N=17) or myelodysplastic
syndrome (N=2)
Peptide
MAGE-A3 or
NY-ESO-1
GM-CSF
Peptide
MUC1
Liposomal MPL
+CYC
Dendritic cell
WT1
High-risk multiple
myeloma, in combination
with chemotherapy and
ASCT
Previously untreated
asymptomatic stage I/II
multiple myeloma or
stage II/III disease in
stable response/plateau
phase
Acute myeloid leukaemia,
in remission following
chemotherapy
NCT00090493
Trials listed on clinicaltrials.gov; accessed September 19 2013. †Adjuvant components are shown in italics. * Phase III study results in shading, otherwise Phase II results; survival data are medians
and comparisons are for active treatment vs. placebo/control, unless otherwise stated.
ASCT: autologous stem cell transplantation; BCG: bacillus Calmette-Guérin; CYC: cyclophosphamide; DC: dendritic cells; DFS: disease-free survival; DTH = delayed type hypersensitivity; GM-CSF:
granulocyte-macrophage colony-stimulating factor; gp100: glycoprotein 100; GST: glutathione-S-transferase; GT: 1,3-galactosyltransferase; HER2: human epidermal growth factor receptor 2);
HPV: human papillomavirus; ICAM-1: intercellular adhesion molecule 1; IMP-3: insulin-like growth factor-II mRNA binding protein 3; IFN-: interferon-; KLH: keyhole limpet hemocyanin; L-BLP25:
BLP25 liposome vaccine; LFA-3: lymphocyte function-associated antigen-3; LY6K: lymphocyte antigen 6 complex locus K; MAGE: melanoma antigen-encoding gene; mCRPC: metastatic, castrateresistant prostate cancer; MPL: monophosphoryl lipid A; MUC1: mucin-1; NHL: non-Hodgkin lymphoma; NS: not significant; NSLC: non-small cell lung cancer; OS: overall survival; PAP: prostatic
acid phosphatase; PBMC: peripheral blood mononuclear cells; PSA: prostate specific antigen; PSCA: prostate stem cell antigen; PSMA: prostate specific membrane antigen; STEAP1: six
transmembrane epithelial antigen of the prostate 1; TGF-β2: transforming growth factor β2; TTK: TTK protein kinase