Clinical evaluation of therapeutic cancer vaccines

Figures & data

Table 1. Approved therapeutic cancer vaccines

Formulation	Product	Company (Country)	Cancer	Status	Completed/Terminated Phase III	Result	References
Dendritic cell	Provenge®	Dendreon Corp. (US)	Prostate cancer	Approval (2010 US), Submission (2011 EU), III ongoing	III D9901	F (Efficacy)	1
					III D9902A	F (Efficacy)	1
					III D9902B, IMPACT	S	30
Dendritic cell	DCVax®-Brain	Northwest Biotherapeutics, Inc. (US)	Glioblastoma	Approval (2007 Switzerland), III ongoing	Not completed	NA	2
Dendritic cell	HybriCell	Genoa Biotechnologia S.A. (Brazil)	Renal cell carcinoma, Melanoma	Approval (2005 Brazil)	Not completed	NA	3
Tumor cell	M-Vax^TM	AVAX Technologies, Inc. (US)	Melanoma	Approval (2005 Switzerland), Approval withdrawal (2002 Australia), III ongoing	III (immunopharmacology)	NA	4,8
Protein	CIMAVax EGF®	Center of Molecular Immunology (Cuba)	Non-small cell lung cancer	Approval (2008 Cuba, Peru), III ongoing	Not completed	Not applicable	6
Peptide	Oncophage® (vitespen)	Agenus, Inc. (US)	Renal cell carcinoma	Approval (2008 Russia), Submission failure (2009 EU)	III C-100–12	F (Efficacy)	5,15

S, success; F, failure

Table 2. Discontinued therapeutic cancer vaccines after Phase III study

Formulation	Product	Company (Country)	Cancer	Status	Completed/Terminated Phase III	Result	References
Tumor cell	CANVAXIN®	Amgen, Inc. (US)	Melanoma	Discontinued	III MMAIT-III	F (Efficacy)	9
					III MMAIT-IV	F (Efficacy)	9
Gene	PANVAC^TM-VF (falimarev)	Therion Biologics Corp. (US)	Pancreatic cancer	Discontinued	III	F (Efficacy)	10
Protein	Theratope®	Oncothyreon Inc. (US)	Breast cancer	Discontinued	III	F (Efficacy)	13
Peptide	Stimuvax® (BLP25)	Oncothyreon, Inc. (US)	Breast cancer	Discontinued	III STRIDE	F (Safety)	18
Anti-idiotypic antibody	Specifid^TM (mitumprotimut-T)	MMRGlobal, Inc. (US)	Non-Hodgkin's lymphoma	Discontinued	III	F (Efficacy)	20
Anti-idiotypic antibody	MyVax®	Genitope Corp. (US)	Non-Hodgkin's lymphoma	Discontinued	III	F (Efficacy)	21
Anti-idiotypic antibody	GM2-KLH vaccine	Progenics Pharmaceuticals, Inc. (US)	Melanoma	Discontinued	III	F (Efficacy)	22
Anti-idiotypic antibody	BEC2	Eli Lilly and Company (US)	Small cell lung cancer	Discontinued	III SILVA	F (Efficacy)	23
Protein	Insegia^TM (G17DT immunogen)	Receptor BioLogix, Inc. (US)	Pancreatic cancer	Unknown	III (single agent)	S	12
					III (combination)	F (Efficacy)	12
Peptide	OTS-102	OncoTherapy Science, Inc. (Japan)	Pancreatic cancer	Unknown	II/III PEGASUS-PC	F (Efficacy)	17
Peptide	Oncophage® (vitespen)	Agenus, Inc. (US)	Melanoma	Unknown	III C-100–21	F (Efficacy)	14

S, success; F, failure

Table 3. Ongoing therapeutic cancer vaccines in Phase III

Formulation	Product	Company (Country)	Cancer	Status	Completed/Terminated Phase III	Result	References
Tumor cell	OncoVAX®	Vaccinogen, Inc. (US)	Colorectal cancer	III ongoing	IIIa 8701	S	7
Tumor cell	Lucanix®	NovaRx Corp. (US)	Non-small cell lung cancer	III ongoing	Not completed	NA	*
Tumor cell	Hyperacute-Pancreatic Cancer Vaccine® (algenpantucel-L)	NewLink Genetics Corp. (US)	Pancreatic cancer	III ongoing	Not completed	NA	*
Gene	Allovectin-7®	Vical Inc. (US)	Melanoma	III (high-dose) ongoing	III (low-dose)	F (Efficacy)	11
Gene	ProstAtak^TM	Advantagene, Inc. (US)	Prostate cancer	III ongoing	Not completed	NA	*
Protein	astuprotimut-γ (MAGE-A3)	GlaxoSmithKline plc (UK)	Non-small cell lung cancer	III ongoing	Not completed	NA	*
			Melanoma	III ongoing	Not completed	NA	*
Peptide	GV1001	KAEL-GemVax Co., Ltd. (South Korea)	Pancreatic cancer	III ongoing	III PriomoVax	F (Efficacy)	16
			Non-small cell lung cancer	III ongoing	Not completed	NA	*
Peptide	Stimuvax® (BLP25)	Oncothyreon, Inc. (US)	Non-small cell lung cancer	III ongoing	III START	F (Efficacy)	*
Peptide	PR1	MD Anderson Cancer Center	Acute myeloid leukemia	III ongoing	Not completed	NA	*
Peptide	NeuVax®	Galena Biopharma, Inc. (US)	Breast cancer	III ongoing	Not completed	NA	*
Peptide	PAS	Cancer Advances Inc. (US)	Pancreatic cancer	III ongoing	Not completed	NA	*
			GIST	III ongoing	Not completed	NA	*
Peptide	IMA901	Immatics biotechnologies GmbH (Germany)	Renal cell carcinoma	III ongoing	Not completed	NA	*
Anti-idiotypic antibody	BiovaxID®	Biovest International, Inc. (US)	Non-Hodgkin's lymphoma	III ongoing	III	S	24,36,37
Anti-idiotypic antibody	racotumomab	Racombio (Spain)	Non-small cell lung cancer	III ongoing	Not completed	NA	*

S, success; F, failure; *Company homepage and / or ClinicalTrials.gov.

Table 4. Reasons of the Phase III failure to primary endpoint with therapeutic cancer vaccine

Product	Cancer	Treatment Position	Regimen	Immune response	Phase III Subset Analysis/Consideration	Suggested Reasons of Phase III Failure	References
Oncophage®	Renal cell carcinoma (Stage I, II, III, IV)	Post-surgical adjuvant 1st line	Single agent	NA	Tumor stage: Subset analysis indicated that intermediate risk patients based on AJCC stage in Oncophage arm might improve RFS and OS. Recurrence events was 19 (15.2%) in stage I or II vs. 31 (27.0%) in observation group. (HR = 0.576; p = 0.056)	Population heterogeneity (Tumor burden)	13,15,25
Oncophage®	Melanoma (Stage IV)	Post-surgical adjuvant 1st line	Single agent	NA	Tumor substage: Exploratory landmark analysis indicated that M1a and M1b, but not M1c, substage patients showed a trend toward increased survival. Combined data from M1a and M1b vs. control was HR = 0.45; 95% CI, 0.21 to 0.96; p = 0.03.	Population heterogeneity (Tumor metastasis)	14,25
PANVAC-VF	Advanced pancreatic cancer (Stage IV)	2nd line (Gemcitabine failure)	Combination with GM-CSF	NA	Study population: OS for 2nd line therapy of pancreatic cancer is less than 3 mo.	Population heterogeneity (Tumor burden)	13,38
Canvaxin®	Melanoma (Stage III)	Post-surgical adjuvant	Combination with BCG	NA	Tumor substage: No stratified data available	Population heterogeneity (Tumor burden, Immunological response)	9,13
					HLA expression: No stratified data available, though potential correlation between HLA and clinical benefit was identified.
Canvaxin®	Melanoma (Stage IV)	Post-surgical adjuvant	Combination with BCG	NA	Tumor substage: No stratified data available	Population heterogeneity (Tumor burden, Immunological response)	9,13
					HLA expression: No stratified data available
GM2-KLH vaccine (GMK)	Melanoma (Stage II)	Post-surgical adjuvant	Combination with QS21	NA	NA	Lack of adjuvant power	26
Theratope®	Metastatic breast cancer	2nd line, CR/PR/SD to chemotherapy	Pre-treatment with cyclophosphamide. Combination with Enhanzyn^TM	NA	Concomitant therapy: Patients received concomitant hormonal therapy showed a trend toward longer OS and TTP. OS was longer in Theratope + hormone therapy and high IgG titers of anti-OSM compared with low IgG titers. (41.1 vs. 25.4 mo ; p = 0.01)	Population heterogeneity (Concomitant therapy)	13,39
BEC2	Small cell lung cancer	2nd line, CR/PR to chemoradiotherapy	Combination with BCG	(Ph III) anti-GD3 response	Humoral response to GD3: The survival of responders was better than that of non-responders.(19.2 mo for responders and 13.9 mo for non-responders; p = 0.0851)	Population heterogeneity (Immunological response)	13,23,33
				(humoral: E) 33%
Allovectin-7®	Metastatic melanoma (Stage III, IV)	1st line combo.	Combination with decarbazine	NA	NA	Lack of dose (Low-dose)	11
Insegia^TM (G17DT immunogen)	Pancreatic cancer	Unsuitable or unwilling to chemotherapy	Single agent	(Ph III) anti-G17 response	Humoral response to G17DT: Patients who developed an anti-G17DT response had significantly improved survival compared with non-responders. (p = 0.003)	Population heterogeneity (Immunological response)	12
				(humoral: E) 73%
	Pancreatic cancer (Stage II, III, IV)	1st line combo.	Combination with gemcitabine	NA	Humoral reponse to G17DT: No data available	Population heterogeneity (Immunological response)	12
Specifid^TM	Non-Hodgkin's lymphoma (WHO grade 1, 2, 3)	CR/PR/SD to rituximab	Combination with GM-CSF	(Ph II) anti-Id response	Tumor stage: No stratified data available, though imbalance in FLIPI was identified.	Population heterogeneity (Tumor burden)	20,21,31,32
				(humoral: E) 20%
				(cellular: I) 72%
MyVax®	Non-Hodgkin's lymphoma (Stage III, IV)	CR/PR to chemotherapy (CVP)	Combination with GM-CSF	(Ph I/II) anti-Id response	MyVax® arm showed a statistically significant difference in PFS between patients who mounted a positive immune response to the tumor-specific target and those who did not.	Population heterogeneity (Immunological response)	21,42,47
				(overall) 62%
				(humoral: E) 48%
				(cellular: T) 44%

NA, not applicable, includes not performed and unknown; E, enzyme-linked immunosorbent assay (ELISA); I, intracellular cytokine staining (ICS); T, T cell proliferation assay

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