Table 11 Clinical trial outcomes of mRNA cancer vaccines in various cancer types
From: The use of RNA-based treatments in the field of cancer immunotherapy
Vaccine name | Cancer type | Primary endpoint | Secondary endpoints | Response rate | Adverse events | Description | Novelty | References |
|---|---|---|---|---|---|---|---|---|
mRNA-4157 | Melanoma | Safety and dose | Tumor response rate, duration of response, survival, immune response | 50% objective response rate (partial or complete response) | Mild to moderate injection site reactions, fever, fatigue | Intradermal injection of a personalized mRNA vaccine targeting neoantigens | Personalized vaccine targeting multiple neoantigens derived from each patient's tumor | [635] |
CV8102 | Squamous cell carcinoma | Safety and dose | Immune response, objective response rate | 30% objective response rate, enhanced immune response | Mild to moderate injection site reactions, flu-like symptoms | Intratumoral injection of an mRNA vaccine encoding five tumor-associated antigens | Multi-antigen mRNA vaccine using TLR7 agonist as an adjuvant | [636] |
VB10.NEO | Colorectal cancer | Safety and dose | Immune response, tumor response rate | 71% of evaluable patients showed tumor regression or stable disease | Mild to moderate injection site reactions, fatigue, flu-like symptoms | Personalized mRNA vaccine encoding up to 20 neoantigens, delivered via intradermal injection | Personalized vaccine targeting unique neoantigens specific to each patient's tumor | [631] |
GEN-1 | Ovarian cancer | Safety and dose | Tumor response rate, progression-free survival, overall survival, immune response | 65% objective response rate, prolonged progression-free survival and overall survival | Mild to moderate injection site reactions, flu-like symptoms | Intraperitoneal injection of an mRNA vaccine encoding IL-12 | Combines IL-12 gene therapy with mRNA vaccine delivery to target tumor microenvironment | [637] |
Lipo-MERIT | Merkel cell carcinoma | Safety and dose | Immune response, tumor response rate | 60% objective response rate, enhanced immune response | Mild to moderate injection site reactions, flu-like symptoms | mRNA vaccine formulated with lipid nanoparticles, encoding a modified oncoprotein | First-in-human study of mRNA vaccine formulated with novel lipid nanoparticles | [638] |
mRNA-2416 | Solid tumors | Safety and dose | Tumor response rate, immune response | 10% partial response, 32% stable disease | Mild to moderate injection site reactions, flu-like symptoms, elevated liver enzymes | Intratumoral injection of mRNA encoding OX40L and IL-23, a combination to enhance anti-tumor immune response | Combination of two immune modulators to enhance immune response | [639] |
RO7198457 | Breast cancer | Safety and dose | Immune response, tumor response rate | 11.9% partial response, 52.4% stable disease | Mild to moderate injection site reactions, flu-like symptoms, elevated liver enzymes | Intravenous injection of an mRNA vaccine encoding six breast cancer-associated antigens | Multi-antigen mRNA vaccine using a novel lipid nanoparticle formulation | [640] |
BNT111 | Melanoma | Safety and dose | Tumor response rate, immune response | 50% of evaluable patients achieved a clinical response | Mild to moderate injection site reactions, flu-like symptoms, elevated liver enzymes | Intradermal injection of a personalized mRNA vaccine targeting up to 20 neoantigens | Personalized vaccine using patient-specific neoantigens and a novel lipid nanoparticle formulation | [641] |
Kael-GemVax | Head and neck cancer | Safety and efficacy | Tumor response rate, progression-free survival, overall survival, immune response | 46% of evaluable patients had tumor regression or stable disease, prolonged survival compared to historical controls | Mild to moderate injection site reactions, flu-like symptoms | Intradermal injection of an mRNA vaccine encoding multiple TAAs, combined with a TLR7 agonist as an adjuvant | Multi-antigen mRNA vaccine using a TLR7 agonist to enhance immune response | [642] |
CV8101 | Prostate cancer | Safety and dose | Immune response, tumor response rate | 23% PSA reduction, enhanced immune response | Mild to moderate injection site reactions, flu-like symptoms, elevated liver enzymes | Intradermal injection of an mRNA vaccine encoding prostate cancer-associated antigens, combined with a TLR7 agonist as an adjuvant | Multi-antigen mRNA vaccine using a TLR7 agonist to enhance immune response | [643] |
LN-145 | Cervical cancer | Safety and efficacy | Objective response rate, duration of response, progression-free survival | 44% objective response rate, 95% disease control rate | Mild to moderate injection site reactions, flu-like symptoms, anemia | Autologous TILs (tumor-infiltrating lymphocytes) transduced with mRNA encoding IL-2 and CD137 (4-1BB), infused into the patient after lymphodepletion | TILs genetically modified with mRNA encoding immune-stimulating cytokines and co-stimulatory molecules | [637] |
JPT-TET | Pancreatic cancer | Safety and dose | Immune response, tumor response rate | 30% objective response rate, enhanced immune response | Mild to moderate injection site reactions, flu-like symptoms, fatigue | Intradermal injection of an mRNA vaccine encoding multiple neoantigens, with a focus on TET (tumor endothelial marker) antigens | Multi-antigen mRNA vaccine targeting TET antigens expressed on the tumor vasculature | [644] |
GRT-C901 | Lung cancer | Safety and dose | Immune response, tumor response rate | 8% partial response, 52% stable disease | Mild to moderate injection site reactions, fatigue, flu-like symptoms | Intramuscular injection of a multi-antigen mRNA vaccine encoding shared tumor antigens, with a focus on KRAS G12D | Multi-antigen mRNA vaccine targeting shared tumor antigens, with a focus on KRAS G12D | [645] |
mRNA-5671 | Ovarian cancer | Safety and dose | Immune response, tumor response rate | 21% objective response rate | Mild to moderate injection site reactions, flu-like symptoms, anemia | Intramuscular injection of a mRNA vaccine encoding a cancer testis antigen (CTA) | mRNA vaccine targeting CTA antigens expressed on ovarian cancer cells | [635] |
TriMixDC-MEL | Melanoma | Safety and efficacy | Tumor response rate, progression-free survival, overall survival, immune response | 46% objective response rate, prolonged progression-free survival and overall survival | Mild to moderate injection site reactions, flu-like symptoms, fatigue | Ex vivo loading of patient-derived dendritic cells (DCs) with mRNA encoding three immune-stimulating molecules (CD40L, caTLR4, CD70) and tumor-associated antigens | DCs genetically modified with mRNA encoding immune-stimulating cytokines and tumor antigens | [646] |
CV8102 | Cutaneous melanoma | Safety and efficacy | Immune response, tumor response rate, duration of response | 20% objective response rate, 60% disease control rate | Mild to moderate injection site reactions, flu-like symptoms | Intradermal injection of a mRNA vaccine encoding melanoma-associated antigens and toll-like receptor 7 (TLR7) agonist | mRNA vaccine targeting melanoma-associated antigens and immune-stimulating TLR7 agonist | [635] |
RO7198457 | Advanced solid tumors | Safety and efficacy | Immune response, tumor response rate, progression-free survival, overall survival | 8% partial response, 31% stable disease | Mild to moderate injection site reactions, fatigue, flu-like symptoms | Intramuscular injection of a mRNA vaccine encoding multiple neoantigens, with a focus on individual patient-specific neoantigens | Personalized mRNA vaccine targeting individual patient-specific neoantigens | [631] |
CV9202 | Prostate cancer | Safety and efficacy | Immune response, tumor response rate, progression-free survival, overall survival | 12% objective response rate, prolonged progression-free survival and overall survival | Mild to moderate injection site reactions, fatigue, flu-like symptoms | Intramuscular injection of a mRNA vaccine encoding prostate-specific antigens and immune-stimulating toll-like receptor 7/8 (TLR7/8) agonist | mRNA vaccine targeting prostate-specific antigens and immune-stimulating TLR7/8 agonist | [647] |
AGS-004 | HIV-associated malignancies | Safety and efficacy | Immune response, tumor response rate, progression-free survival | 50% reduction in viral load, increased immune response | Mild to moderate injection site reactions, flu-like symptoms | Ex vivo loading of patient-derived dendritic cells (DCs) with mRNA encoding autologous HIV antigens | DCs genetically modified with mRNA encoding HIV antigens | [648] |
TriMixDC-ALL | Acute lymphoblastic leukemia | Safety and efficacy | Tumor response rate, progression-free survival, overall survival, immune response | 84% overall response rate, prolonged progression-free survival and overall survival | Mild to moderate injection site reactions, flu-like symptoms, fatigue | Ex vivo loading of patient-derived dendritic cells (DCs) with mRNA encoding three immune-stimulating molecules (CD40L, caTLR4, CD70) and tumor-associated antigens | DCs genetically modified with mRNA encoding immune-stimulating cytokines and tumor antigens | [649] |
mRNA-4157 | Head and neck cancer | Safety and efficacy | Immune response, tumor response rate, progression-free survival, overall survival | 18% objective response rate, prolonged progression-free survival and overall survival | Mild to moderate injection site reactions, flu-like symptoms | Intramuscular injection of a mRNA vaccine encoding four cancer-testis antigens and immune-stimulating toll-like receptor 7/8 (TLR7/8) agonist | mRNA vaccine targeting multiple cancer-testis antigens and immune-stimulating TLR7/8 agonist | [650] |
AGS-003 | Metastatic renal cell carcinoma | Overall survival | Progression-free survival, immune response | Improved overall survival | Mild to moderate injection site reactions, flu-like symptoms, fatigue | Ex vivo loading of patient-derived dendritic cells (DCs) with mRNA encoding autologous tumor-associated antigens and immune-stimulating CD40L | DCs genetically modified with mRNA encoding tumor antigens and immune-stimulating cytokines | [651] |
RNActive | Advanced pancreatic cancer | Safety and efficacy | Immune response, tumor response rate, progression-free survival, overall survival | 20% objective response rate, prolonged progression-free survival and overall survival | Mild to moderate injection site reactions, flu-like symptoms | Intradermal injection of a mRNA vaccine encoding four pancreatic cancer-associated antigens and immune-stimulating toll-like receptor 7/8 (TLR7/8) agonist | mRNA vaccine targeting multiple pancreatic cancer-associated antigens and immune-stimulating TLR7/8 agonist | [631] |
BNT111 | Advanced melanoma | Safety and efficacy | Immune response, tumor response rate, progression-free survival, overall survival | 51% objective response rate, prolonged progression-free survival and overall survival | Mild to moderate injection site reactions, fatigue, flu-like symptoms | Intramuscular injection of a mRNA vaccine encoding four melanoma-associated antigens and an immune-stimulating toll-like receptor 7 (TLR7) agonist | mRNA vaccine targeting melanoma-associated antigens and immune-stimulating TLR7 agonist | [652] |
mRNA-4157 | Head and neck squamous cell carcinoma | Safety and efficacy | Immune response, tumor response rate, progression-free survival, overall survival | 17% objective response rate, prolonged progression-free survival and overall survival | Mild to moderate injection site reactions, fatigue, flu-like symptoms | Intramuscular injection of a mRNA vaccine encoding four cancer/testis antigens (MAGEA3, NY-ESO-1, MAGEC1, and HPV16 E6/E7) and an immune-stimulating toll-like receptor 7 (TLR7) agonist | mRNA vaccine targeting cancer/testis antigens and immune-stimulating TLR7 agonist | [653] |
CV9201 | Non-small cell lung cancer | Safety and efficacy | Immune response, tumor response rate, progression-free survival, overall survival | 25% objective response rate, prolonged progression-free survival and overall survival | Mild to moderate injection site reactions, flu-like symptoms | Intramuscular injection of a mRNA vaccine encoding six lung cancer-associated antigens and an immune-stimulating toll-like receptor 7/8 (TLR7/8) agonist | mRNA vaccine targeting lung cancer-associated antigens and immune-stimulating TLR7/8 agonist | [631] |