Therapeutic tumor vaccines — a rising star to benefit cancer patients

Table 1 Selected list of tumor vaccine under recruitment in clinical trials

Vaccine type		Disease	Combination	Phase	NCT ID
Tumor cell vaccine	GVAX	Neuroblastoma. Pediatric Solid Tumor	Nivolumab. Ipilimumab	Phase I	NCT04239040
		Locally Advanced Pancreatic Ductal Adenocarcinoma	Nivolumab CCR2/CCR5 dual antagonist	Phase I; Phase II	NCT03767582
		Metastatic Pancreatic Adenocarcinoma	Epacadostat. Pembrolizumab CRS-207 CY	Phase II	NCT03006302
		Colorectal Cancer		Phase I	NCT01952730
	GVAX Pancreas Vaccine	Pancreatic Cancer	Cyclophosphamide Nivolumab	Phase II	NCT03161379
		Pancreatic Cancer	Cyclophosphamide Nivolumab Urelumab	Phase I; Phase II	NCT02451982
	GM-CSF vaccine	Multiple Myeloma	Lenalidomide Prevnar13	Phase II	NCT03376477
DC Vaccine	AST-VAC2	NSCLC in the Advanced and Adjuvant Settings		Phase I	NCT03371485
	MIDRIXNEO	NSCLC	Antigen-specific DTH. Control DTH	Phase I	NCT04078269
	Autologous Dendritic Cell-Adenovirus CCL21 Vaccine	NSCLC Stage IV, IVA, IVB Lung Cancer AJCC v8	Pembrolizumab	Phase I	NCT03546361
	Autologous DCs: MESOVAX	Mesothelioma. Malignant PD-L1 Negative Advanced Cancer Progressive Disease	Pembrolizumab. Interleukin-2	Phase I	NCT03546426
	PEP-DC vaccine	Pancreatic Adenocarcinoma		Phase I	NCT04627246
	ME TARP vaccine	Prostate Cancer		Phase II	NCT02362451
	DC/AML Fusion Vaccine	Acute Myelogenous Leukemia	Decitabine	Phase I	NCT03679650
		Acute Myelogenous Leukemia		Phase II	NCT03059485
	mDC3/8-KRAS Vaccine	Pancreatic Ductal Adenocarcinoma		Phase I	NCT03592888
	Autologous DC vaccine: RaC-Ad	Head Neck Tumors, Neuroendocrine Tumors, Soft Tissue Sarcoma Rare Cancer	Interleukin-2	Phase II	NCT04166006
	COREVAX-1	Stage IV Colorectal Cancer Curative Resection	Interleukin-2	Phase II	NCT02919644
	Autologous DCs + Prevnar 13	Stage III, IIIA, IIIB, IV, IVA, IVB Hepatocellular Carcinoma AJCC v8, Stage III, IIIA, IIIB, IV Intrahepatic Cholangiocarcinoma AJCC v8, Unresectable Hepatocellular Carcinoma, Unresectable Intrahepatic Cholangiocarcinoma	Radiation: External Beam Radiation Therapy	Early Phase I	NCT03942328
	DC Tumor Cell Lysate Vaccine: ATL-DC	Recurrent Glioblastoma	Pembrolizumab poly-ICLC	Phase I	NCT04201873
	Dendritic Cell/Tumor Fusion Vaccine	Glioblastoma, Neuroectodermal Tumors	Interleukin-12 Temozolomide	Phase I; Phase II	NCT04388033
	DC1 Vaccine+ WOKVAC Vaccine	Female Breast Cancer, Male Breast Cancer, Stage I, II, III Breast Cancer, HER2-positive Breast Cancer		Phase II	NCT03384914
	neoantigen-primed DC vaccine	Gastric Cancer, Hepatocellular Carcinoma, NSCLC, Colon Rectal Cancer		Phase I	NCT04147078
	MG-7-DC vaccine	Later stage of gastric cancer	Sintilimab	Phase I; Phase II	NCT04567069
	IKKb matured, RNA-loaded DC vaccine	Melanoma, Uveal Metastatic		Phase II	NCT04335890
Peptide vaccine	UCPVax: VolATIL	Squamous Cell Carcinoma of the Head and Neck, Anal Canal Cancer, Cervical Cancer	Atezolizumab	Phase II	NCT03946358
	UCPVax-Glio	Glioblastoma		Phase I; Phase II	NCT04280848
	UCPVax	Metastatic NSCLC		Phase I; Phase II	NCT02818426
	MUC1	NSCLC	PolyICLC	Phase I; Phase II	NCT01720836
	SVN53-67/M57-KLH	Lung Atypical Carcinoid Tumor, Lung Typical Carcinoid Tumor, Metastatic Pancreatic Neuroendocrine Tumor	Incomplete Freund's Adjuvant Octreotide Acetate Sargramostim	Phase I	NCT03879694
	NSABP FB-14/AE37	Triple-negative Breast Cancer	Pembrolizumab	Phase II	NCT04024800
	KRAS peptide vaccine	Colorectal Cancer, Pancreatic Cancer	Nivolumab Ipilimumab	Phase I	NCT04117087
	da VINc/OTSGC-A24	Gastric Cancer	Nivolumab Ipilimumab	Phase I	NCT03784040
	ARG1-18, 19, 20	NSCLC, Urothelial Carcinoma, Malignant Melanoma, Ovarian Cancer, Colorectal Cancer, Breast Cancer, Squamous Cell Carcinoma of the Head and Neck, Metastatic Cancer		Phase I	NCT03689192
	Personalized peptide vaccine	Stage IV, IVA, IVB Colorectal Cancer AJCC v7, Stage IV Pancreatic Cancer AJCC v6 and v7	Imiquimod Pembrolizumab	Phase I	NCT02600949
	WT1/NY-ESO-1	Ovarian Cancer, Fallopian Tube Primary Peritoneal Cancer, Recurrent Ovarian Cancer	Nivolumab	Phase I	NCT02737787
	IMU-131/HER-Vaxx	Gastrointestinal Neoplasms, Adenocarcinoma	Cisplatin and either Fluorouracil (5-FU) or Capecitabine or Oxaliplatin and capecitabine	Phase I; Phase II	NCT02795988
	ESR1	Breast Cancer		Phase I	NCT04270149
	DNAJB1-PRKACA	Fibrolamellar, Hepatocellular Carcinoma	Nivolumab Ipilimumab	Phase I	NCT04248569
	H3.3K27M	Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, H3 K27M-Mutant	Nivolumab	Phase I; Phase II	NCT02960230
	H2NVAC	Ductal Breast Carcinoma In Situ	Granulocyte Macrophage Colony Stimulating Fator	Phase I	NCT04144023
	IDH1R132H/AMPLIFY-NEOVAC	Malignant Glioma	Avelumab	Phase I	NCT03893903
DNA Vaccine	pTVG-HP/pTVG-AR	CRPC, Metastatic Cancer	Pembrolizumab rhGM-CSF	Phase II	NCT04090528
	Mammaglobin-A	Breast Cancer		Phase I	NCT02204098
	pTVG-HP	Prostate Cancer	Nivolumab GM-CSF	Phase II	NCT03600350
	pNGVL4a-Sig/E7(detox)/HSP70	Cervical Cancer, Precancerous Condition, HPV Disease, Human Papilom-virus	Imiquimod	Phase I	NCT00788164
	Salmonella oral vaccine	Relapsed Neuroblastoma	Lenalidomide	Early Phase I	NCT04049864

NSCLC: Non-small cell lung cancer; CRPC: Castration-resistant prostate cancer; AJCC: American Joint Committee on Cancer; GM-CSF: Granulocyte-macrophage colony stimulating factor.

Table 2 Typical mRNA-based tumor vaccines

Vaccine	mRNA-encoded antigen	Formulation type	Disease	NCT ID	Phases	Status	Sponsor/collaborator	Results
mRNA-2416	OX40L	LNP	Relapsed/Refractory Solid Tumor Malignancies or Lymphoma Ovarian Cancer	NCT03323398	Phase I/II	Recruiting	ModernaTX, Inc.	Any dose of intratumoral injection is tolerable when mRNA-2416 is administered alone. Results indicate increased OX40L protein expression, elevated PD-L1 levels and pro-inflammatory activity after mRNA-2416 injection
mRNA-2572	OX40L, IL-23, IL-36γ	LNP	Dose Escalation: Relapsed/Refractory Solid Tumor Malignancies or Lymphoma Dose Expansion: Triple Negative Breast Cancer, Head and Neck Squamous Cell Carcinoma, Non-Hodgkin Lymphoma, and Urothelial Cancer	NCT03739931	Phase I	Recruiting	ModernaTX, Inc., AstraZeneca	Any dose of intratumoral injection is tolerable when mRNA-2572 is administered alone or in combination with PD-L1 inhibitor. IFN-γ, TNF-α, and PD-L1 levels increased
mRNA-4157 KEYNOTE-603	Neo-Ag	LNP	Solid Tumors	NCT03313778	Phase I	Recruiting	ModernaTX, Inc., Merck Sharp & Dohme Corp.	All tested doses is tolerated, and clinical responses were observed when mRNA-4157 is combined with Pembrolizumab
KEYNOTE-942	Neo-Ag	LNP	Melanoma	NCT03897881	Phase II	Recruiting	ModernaTX, Inc., Merck Sharp & Dohme Corp.	Not available
mRNA-5671/Merck V941	KRAS mutations: G12D, G12V, G13D, G12C	LNP	NSCLC, Pancreatic cancer, Colorectal cancer	NCT03948763	Phase I	Recruiting	Merck Sharp & Dohme Corp.	Not available
FixVac (BNT111); Lipo-MERIT	NY-ESO-1, MAGEC3, tyrosinase, TPTE	Lipo-MERIT, LNP	Melanoma	NCT02410733	Phase I	Active, not recruiting	BioNTech SE	BNT111 alone or in combination with PD1, mediates durable objective responses in CPI-experienced patients with unresectable melanoma. Durable clinical responses in both monotherapy and combination with CPI are accompanied by the induction of strong CD4+ and CD8+ T cell immunity. BNT111 vaccination was safe and well tolerated with no dose limiting toxicity
RO7198457 (BNT122)	Neo-Ag	Lipo-MERIT, LNP	Melanoma, NSCLC, Bladder Cancer, CRC, Breast Cancer etc.	NCT03289962	Phase I	Recruiting	BioNTech, Genentech	The combination of RO7198457 and atezolizumab is generally well tolerated. RO7198457 combined with atezolizumab can induce pro-inflammatory cytokine release and peripheral T cell response in most patients
	Neo-Ag	Lipo-MERIT, LNP	Advanced Melanoma	NCT03815058	Phase II	Recruiting	Genentech, Inc., BioNTech SE	Not available
	Neo-Ag	Lipo-MERIT, LNP	Stage II and III CRC (surgically resected)	NCT04486378	Phase II	Recruiting	BioNTech SE	Not available
	Neo-Ag	Lipo-MERIT, LNP	Pancreatic Cancer (surgically resected)	NCT04161755	Phase I	Recruiting	Memorial Sloan Kettering Cancer Center, Genentech, Inc.	Not available
	Neo-Ag	Lipo-MERIT, LNP	NSCLC	NCT04267237	Phase II	Withdrawn	Hoffmann-La Roche	Not available
SAR441000 (BNT131)	IL-12sc, IL-15sushi, IFNα and GM-CSF	Various formulations	advanced melanoma	NCT03871348	Phase I	Recruiting	Sanofi, BioNTech RNA Pharmaceuticals GmbH	Not available
RiboMab (BNT141)	mRNA encoding secreted IgG antibodies that target multiple epithelial solid tumors	Various liver-targeting LNP formulations	CLDN18.2-positive Solid Tumors	NCT04683939	Phase I/II	Not yet recruiting	BioNTech SE	Not available
IVAC MUTANOME, RBL001/RBL002	Neo-Ag/TAA	naked mRNA	Advanced Melanoma	NCT02035956	Phase I	Completed	BioNTech RNA Pharmaceuticals GmbH, BioNTech SE
CV8102	TLR7/8/RIG-1 agonist based on noncoding single stranded RNA	RNActive, (Protamine)	Melanoma (Skin), Squamous Cell Carcinoma of the Skin Carcinoma, Squamous Cell of Head and Neck Carcinoma, Adenoid Cystic	NCT03291002	Phase I	Recruiting	CureVac AG, Syneos Health	Not available
	Peptide vaccine and mRNA	IMA970A plus CV8102 and Cyclophosphamide	Hepatocellular carcinoma	NCT03203005	Phase I/II	Completed	National Cancer Institute, Naples, immatics Biotechnologies GmbH, CureVac AG, European Commission-FP7-Health-2013- Innovation-1	Not available
BI-1361849 (CV9202)	NY-ESO-1, MAGE-C2, MAGE-C1, survivin, 5 T4, MUC1	RNActive, Protamine	Metastatic NSCLC	NCT03164772	Phase I/II	Active, not recruiting	Ludwig Institute for Cancer Research, Cancer Research Institute, New York City; Boehringer Ingelheim, MedImmune LLC, CureVac AG, PharmaJet, Inc.	CV9202 was well-tolerated, and antigen specific immune responses were detected in majority of patients (84%)
CV9201	MAGE-C1, MAGE-C2, NY-SEO-1, survivin,5 T4	RNActive, Protamine	Stage IIIB/IV NSCLC	NCT00923312	Phase I/II	Completed	CureVac AG	CV9201 was well-tolerated and results indicated immune responses after vaccination. Median PFS and OS were 5 and 10.8 mo, respectively
CV9103	PSA, PSCA, PSMA, STEAP1	RNActive, Protamine	Prostate cancer	NCT00831467	Phase I/II	Completed	CureVac AG	CV9103 is well tolerated and immunogenic
CV9104	PSA, PSCA, PSMA, STEAP1, PAP, MUC1	RNActive, Protamine	Prostate cancer	NCT01817738	Phase I/II	Terminated	CureVac AG	Terminated due to insufficient activities

LNP: Lipid Nanoparticle; Neo-Ag: Neoantigen; IFN-γ: Interferon-γ; TNF-α: Tumor necrosis factor-α; PD-L1: Programmed death-ligand 1; IL: Interleukin; GM-CSF: Granulocyte-macrophage colony stimulating factor; NSCLC: Non-small cell lung cancer.

Table 3 Typical mRNA-based coronavirus disease 2019 vaccines have entered phase III or IV clinical trials

Vaccine	NCT ID	Title	Phase	Status	Estimated number of participants	Sponsor/collaborator
BNT162b2	NCT04816669	Study to Evaluate the Safety, Tolerability, and Immunogenicity of a Lyophilized Formulation of BNT162b2 Against COVID-19 in Healthy Adults	Phase III	Recruiting	550	BioNTech SE, Pfizer
	NCT04713553	A Phase 3 Study to Evaluate the Safety, Tolerability, and Immunogenicity of Multiple Production Lots and Dose Levels of BNT162b2 Against COVID-19 in Healthy Participants	Phase III	Recruiting	1530	BioNTech SE, Pfizer
	NCT04754594	Study to Evaluate the Safety, Tolerability, and Immunogenicity of SARS-CoV-2 RNA Vaccine Candidate (BNT162b2) Against COVID-19 in Healthy Pregnant Women 18 Years of Age and Older	Phase II/III	Recruiting	4000	BioNTech SE, Pfizer
	NCT04775069	Antibody Response to COVID-19 Vaccines in Liver Disease Patients	Phase IV	Not yet recruiting	900	Humanity & Health Medical Group Limited
mRNA-1273	NCT04860297	A Study to Evaluate Safety and Immunogenicity of mRNA-1273 Vaccine to Prevent COVID-19 in Adult Organ Transplant Recipients and in Healthy Adult Participants	Phase III	Recruiting	240	ModernaTX, Inc.
	NCT04796896	A Study to Evaluate Safety and Effectiveness of mRNA-1273 Vaccine in Healthy Children Between 6 Months of Age and Less Than 12 Years of Age	Phase II/III	Recruiting	6750	ModernaTX, Inc.
	NCT04470427	A Study to Evaluate Efficacy, Safety, and Immunogenicity of mRNA-1273 Vaccine in Adults Aged 18 Years and Older to Prevent COVID-19	Phase III	Active, not recruiting	30420	ModernaTX, Inc., Biomedical Advanced Research and Development Authority, National Institute of Allergy and Infectious Diseases (NIAID)
	NCT04649151	A Study to Evaluate the Safety, Reactogenicity, and Effectiveness of mRNA-1273 Vaccine in Adolescents 12 to <18 Years Old to Prevent COVID-19	Phase II/III	Active, not recruiting	3000	ModernaTX, Inc., Biomedical Advanced Research and Development Authority
CV-NCOV-011	NCT04848467	A Trial Studying the SARS-CoV-2 mRNA Vaccine CVnCoV to Learn About the Immune Response, the Safety, and the Degree of Typical Vaccination Reactions When CVnCoV is Given at the Same Time as a Flu Vaccine Compared to When the Vaccines Are Separately Given in Adults 60 Years of Age and Older (CV-NCOV-011)	Phase III	Not yet recruiting	1000	Bayer, CureVac AG
CVnCoV	NCT04860258	A Study to Evaluate Safety, Reactogenicity and Immunogenicity of the SARS-CoV-2 mRNA Vaccine CVnCoV in Adults With Co-morbidities for COVID-19	Phase III	Not yet recruiting	1200	CureVac AG
	NCT04838847	A Study to Evaluate the Immunogenicity and Safety of the SARS-CoV-2 mRNA Vaccine CVnCoV in Elderly Adults Compared to Younger Adults for COVID-19	Phase III	Not yet recruiting	180	CureVac AG
	NCT04652102	A Study to Determine the Safety and Efficacy of SARS-CoV-2 mRNA Vaccine CVnCoV in Adults for COVID-19	Phase II/III	Recruiting	36500	CureVac AG
	NCT04674189	A Study to Evaluate the Safety and Immunogenicity of Vaccine CVnCoV in Healthy Adults in Germany for COVID-19	Phase III	Recruiting	2520	CureVac AG
SARS-CoV-2 mRNA Vaccine	NCT04847102	A Phase III Clinical Study of a SARS-CoV-2 Messenger Ribonucleic Acid (mRNA) Vaccine Candidate Against COVID-19 in Population Aged 18 Years and Above	Phase III	Not yet recruiting	28000	Walvax Biotechnology Co., Ltd., Abogen Biosciences Co. Ltd., Yuxi Walvax Biotechnology Co., Ltd.,
CoVPN 3006	NCT04811664	A Study of SARS CoV-2 Infection and Potential Transmission in University Students Immunized With Moderna COVID-19 Vaccine (CoVPN 3006)	Phase III	Recruiting	37500	National Institute of Allergy and Infectious Diseases (NIAID)
KYRIOS	NCT04869358	Exploring the Immune Response to SARS-CoV-2/COVID-19 Vaccines in Patients With Relapsing Multiple Sclerosis (RMS) Treated With Ofatumumab (KYRIOS)	Phase IV	Not yet recruiting	40
ENFORCE	NCT04760132	National Cohort Study of Effectiveness and Safety of SARS-CoV-2/COVID-19 Vaccines (ENFORCE) (ENFORCE)	Phase IV	Recruiting	10000	Jens D Lundgren, MD, Ministry of the Interior and Health, Denmark; Rigshospitalet, Denmark
AMA-VACC	NCT04792567	Exploring the Immune Response to SARS-CoV-2 modRNA Vaccines in Patients With Secondary Progressive Multiple Sclerosis (AMA-VACC) (AMA-VACC)	Phase IV	Recruiting	60
COVAXID	NCT04780659	COVID-19 Vaccination of Immunodeficient Persons (COVAXID) (COVAXID)	Phase IV	Recruiting	540	Karolinska University Hospital, Karolinska Institutet
DemiVac	NCT04852861	Safety and Immunogenicity of Demi-dose of Two Covid-19 mRNA Vaccines in Healthy Population (DemiVac)	Phase IV	Not yet recruiting	200	Sciensano, Mensura EDPB, Institute of Tropical Medicine, Belgium; Erasme University Hospital

COVID-19: Coronavirus disease 2019; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2.