Supplementary Table 1. Active Immunotherapies in Phase II Development

Supplementary Table 1. Active immunotherapies in phase II development

Type of immunotherapy / Antigens / Adjuvants/
immune modulators / Study population / Patients(N) / Efficacy results* / Citation
Prostate cancer
Viral vector (vaccinia/ fowlpox prime/boost): Prostvac®-VF / PSA / GM-CSF + co-stimulators / Metastatic, castration-resistant prostate cancer / 125 / 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 / Kantoff, P. W. et al. J. Clin. Oncol.28, 1099-1105 (2010).NCT01322490
Viral vector (adenovirus) / PSA / Vector / Recurrent/hormone-refractory prostate cancer / 44 / Clinical
Increase in PSA doubling time in 64% of patients
Immunologic
Tcell response: 100% (recurrent disease) and 67% (hormone-refractory disease) of patients / Lubaroff, D. M. et al. Cancer Res. 72, Abstr 2692 (2012).
mRNA:
CV9103/9104, CureVac® / PSA + PSCA +
PSMA + STEAP1 / mRNA / Metastatic, castration-resistant prostate cancer / 38 / Clinical
Prolonged stabilization of PSA levels for individual patients
Immunologic
Tcell response: 79% of patients, 58% with multiepitope responses / Kübler, H. et al. J. Clin. Oncol.29 suppl., Abstr 4535 (2011).
Breast cancer
Peptide:
nelipepimut-S (E75), NeuVax™ / HER2 / GM-CSF / High-risk breast cancer, in remission after standard treatment / 182 / 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) / Mittendorf, E. A. et al. Cancer. 118, 2594-2602(2012).NCT01479244
Peptide:
GP2 / HER2 / GM-CSF / High-risk breast cancer, in remission after standard treatment / 172 / Clinical
Recurrence rate: 4.3% vs. 11.6% (P=0.41)
Immunologic
DTH: 21.5 vs. 6.0 mm (P<0.01) / Trappey, F. et al. J. Clin. Oncol.31, Abstr 3005 (2013).
Lung cancer
Peptide:
CIMAvax EGF / EGFR / Montanide ISA51 + CYC / Stage IIIB/IV NSCLC, after chemotherapy / 80 / 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 / NeningerVinageras E. et al. J ClinOncol.26, 1452-1458 (2008).NCT01444118
Peptide:
GV1001 / Telomerase / GM-CSF / Unresectable stage III NSCLC; after chemoradiotherapy / 23 / 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
Tcell response: 16/23 patients (69.6%) / Brunsvig, P. F. et al. Clin. Cancer Res.17, 6847-6857 (2011).NCT01579188
Viral vector (vaccinia):
TG4010 / MUC1 / Vector + IL-2 / Stage IV NSCLC, with chemotherapy / 148 / 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 / Quoix, E. et al. Lancet Oncol. 12, 1125-1133 (2011).NCT01383148
Allogeneic tumour cell:
belagenpumatucel-L, Lucanix™ / Tumour cell / Anti-TGF-β / Stage II–IV NSCLC; after front-line chemotherapy / 75 / Clinical
OS: 14.4 mo; longer survival with higher (19.1 mo) vs. low (8.3 mo; P=0.0186) dose immunization / Nemunaitis, J. et al. J. Clin. Oncol.24, 4721-4730 (2006).NCT00676507
Allogeneic tumour cell: tergenpumatucel-L, HyperAcute® Lung / Tumour cell / αGT / Stage IIIB/IV NSCLC; progressive or relapsed after chemotherapy / 28 / 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 / Morris, J. C. et al. J. Clin. Oncol.30suppl, Abstr 2571 (2012).NCT01774578
Anti-idiotype: racotumomab / Idiotype / Alum / Stage IIIB/IV NSCLC; after primary treatment / 176 / Clinical
OS: 8.3 mo vs. 6.3 mo (P=0.02) / Macías, A. et al. Ann. Oncol.23suppl 9, Abstr 1238PD (2012). NCT014604722
Melanoma
Peptide / survivin / Montanide ISA51 + CYC / Metastatic, treatment-refractory stage IV melanoma / 61 / 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
Tcell responses in 13/41 (32%) patients / Becker, J. C. et al. Cancer Immunol. Immunother.61, 2091-2103 (2012).
Peptide / gp100 + MART-1 + tyrosinase / GM-CSF + Montanide ISA51 / Metastatic melanoma / 22 / Clinical
OS: 13.4 mo
PFS: 1.9 mo
Immunologic
Tcell responses in 9/20 (45%) patients / Tarhini, A. A. et al. J. Immunother.35, 359-366 (2012).
Dendritic cell / gp100 + MAGE-A1, A2, A3 + MART-1 + tyrosinase / KLH / Metastatic melanoma / 24 / 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
Tcell responses in 18/24 (75%) patients; multiepitope responses in 13/24 (54%) patients / Oshita, C. et al. Oncol. Rep.28, 1131-1138 (2012).
Dendritic cell / gp100 + tyrosinase (MHC-I/II) / KLH / Stage III/IV melanoma / 33 / 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
Tcell responses in 5/29 (17%) patients / Aarntzen, E. H. et al. Cancer Res.73, 19-29 (2013).
Dendritic cell / survivin + telomerase + p53 / IL-2 + CYC +celecoxib / Metastatic melanoma / 28 / Clinical
OS: 9.4 mo
Immunologic
Antigen-specific responses in 9/15 (60%) patients / Ellebaek, E. et al. Cancer Immunol. Immunother.61, 1791-1804 (2012).
Autologous tumour cell:
MVax / Hapten-modified tumour cells / BCG + IL2 + CYC / Metastatic melanoma / 97 / 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 / Berd, D. et al. Int. J. Cancer. 94, 531-539 (2001).NCT00477906
Allogeneic tumour cell / Shed-antigens / Alum / Stage IIB/C or III melanoma; post-surgery / 38 / Clinical
OS: 45.6 mo vs.32.4 mo (P=NS)
Recurrence-free survival: 19.2 mo vs. 7.2 mo (P=0.03) / Bystryn, J. C. et al. Clin. Cancer Res.7, 1882-1887 (2001).NCT01546571
Allogeneic tumour cell / Tumour cell / BCG + GM-CSF / Stage IIB/C or III melanoma; post-surgery / ≈108 / – / NCT01729663
Viral vector (vaccinia/ fowlpox prime/boost): Prostvac®-VF / NY-ESO-1 / Vector / Stage III/IV melanoma / 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+ Tcell responses in 22/25 (88%) patients / Odunsi, K. et al. Proc. Natl. Acad. Sci. USA.109, 5797-5802 (2012).
Pancreatic cancer
Peptide / ras peptides / GM-CSF / Advanced/surgically resected pancreatic cancer / 48 / Clinical
OS
Immune responders vs. non-responders: 4.8 mo vs. 2.0 mo (P=0.0002)
Immunologic
Tcell responses in 17/43 (40%) patients / Gjertsen, M. K. et al. Int. J. Cancer. 92, 441-450 (2001).
Allogeneic tumour cell:
algenputacel-L HyperAcute® Pancreas / Tumour cell / α-GT / Surgically resected pancreatic cancer, with chemoradiotherapy / 70 / Clinical
1, 2 and 3-yr survival of 86%, 51% and 42%, respectively / Hardacre, J. M. et al. J. Gastrointest. Surg.17, 94-100 (2013).NCT01836432, NCT01072981
Colorectal cancer
Viral vector (adenovirus) / CEA / Vector / Metastatic colorectal cancer / 32 / Clinical
1-yr survival of 48%
Immunologic
Tcell responses in 15/32 (47%) patients / Morse, M. A. et al. Cancer Immunol. Immunother.62, 1293-1301 (2013).
Dendritic cell
Modified with CEA + MUC1-encoding poxvector (PANVAC) / CEA + MUC1/GM-CSF / Resected metastatic colorectal cancer; after resection (N=74) / 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. Ann. Surg.258, 879-886 (2013).
Renal cell carcinoma
Peptide:
IMA901 / PLIN2 + APOL1 + CCND1 + GUCY1A3 + PRUNE2 + MET + MUC1 + RGS5 + MMP7 + HBcAg / GM-CSF ± CYC / Metastatic RCC / 68 / 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
Tcell responses in 20/27 (74%) patients; multiepitope responses in 8/27 (30%) patients / Walter, S. et al. Nat. Med.18, 1254-1261 (2012).NCT01265901
Dendritic cell:
AGS-003 / Tumour cell RNA / CD40L / Metastatic RCC / 21 / Clinical
OS: 30.2 mo
PFS: 11.2 mo / Amin, A. et al. J. Clin. Oncol.31suppl, Abstr 357 (2013).NCT01582672
Haematologic malignancies
Peptide / WT1 / GM-CSF + KLH / Acute myeloid leukaemia (N=17) or myelodysplastic syndrome (N=2) / 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
Tcell responses in 8/18 (44%) patients / Keilholz, U. et al. Blood. 113, 6541-6548 (2009).
Peptide / MAGE-A3 or NY-ESO-1 / GM-CSF / High-risk multiple myeloma, in combination with chemotherapy and ASCT / – / NCT00090493
Peptide / MUC1 / Liposomal MPL +CYC / Previously untreated asymptomatic stage I/II multiple myeloma or stage II/III disease in stable response/plateau phase / 34 / Clinical
Reduction in slope of paraprotein concentration in 13/29 patients
Immunologic
Tcell responses in 15/32 (47%) of patients / Rossmann, E. et al. American Society of Hematology Annual Meeting. Abstr 2927 (2011).
Dendritic cell / WT1 / Acute myeloid leukaemia, in remission following chemotherapy / 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).

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, castrate-resistant 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