Table 1.
List of all active, and completed or terminated phase II/III clinical trials of mRNA vaccines in cancer therapy
| Sponsor | Vaccine type (delivery route) | Indication | ClinicalTrial.gov identifier (phase, allocation) | Combination | Opened | Status |
|---|---|---|---|---|---|---|
| DC vaccine | ||||||
| Antwerp University Hospital | WT1 mRNA (i.d.) | Myeloid leukemia, multiple myeloma | NCT00965224 (II, randomized) | Standard-of-care | 2009 | Unknown [27] |
| AML | NCT01686334 (II, randomized) | Conventional chemotherapy | 2012 | Recruiting | ||
| GBM | NCT02649582 (I/II) | Temozolomide, temozolomide-based chemoradiation | 2015 | Recruiting | ||
| Malignant pleural mesothelioma | NCT02649829 (I/II) | Conventional chemotherapy | 2017 | Recruiting | ||
| Argos Therapeutics | Total tumor mRNA and CD40L mRNA (i.d.) | RCC | NCT00678119 (II, single arm) | Standard-of-care (sunitinib) | 2008 | Completed [28] |
| NCT01582672 (III, randomized) | 2012 | Terminated (Lack of effiacy) [29, 30] | ||||
| Asterias Biotherapeutics, Inc. | hTERT mRNA with a LAMP-1 targeting sequence (i.d.) | AML (complete remission) | NCT00510133 (II, single arm) | None | 2007 | Completed [31] |
| Baylor College of Medicine | Tumor mRNA and tumor lysate (i.d.) | Pancreatic cancer | NCT04157127 (I) | Adjuvant to chemotherapy | 2020 | Recruiting |
| Duke University | LAMP-fused HCMV pp65 mRNA (i.d.) and td | Malignant neoplasms of brain | NCT00639639 (I) | None | 2006 | Active, not recruiting [32] |
| NCT02366728 (II, randomized) | Temozolomide, basiliximab (antagonistic anti-CD25) | 2015 | Active, not recruiting [33] | |||
| Glioblastoma | NCT03688178 (II, randomized) | Temozolomide, varlilumab (agonistic anti-CD27) | 2020 | Recruiting | ||
| LAMP-fused HCMV pp65 mRNA, GM-CSF (i.d.) and td | Malignant neoplasms of brain | NCT03615404 (I) | None | 2018 | Active, not recruiting | |
| Glioblastoma | NCT03927222 (II, single arm) | Temozolomide | 2019 | Recruiting | ||
| Guangdong 999 Brain Hospital | Tumor mRNA | Brain cancer, neoplasm metastasis | NCT02808416 (I) | None | 2016 | Active, not recruiting |
| Recurrent glioblastoma | NCT02808364 (I) | None | 2016 | Active, not recruiting | ||
| Glioblastoma TAA mRNA (i.d. and i.v.) | Glioblastoma | NCT02709616 (I) | Conventional chemo- and radiotherapy | 2016 | Active, not recruiting | |
| Hasumi International Research Foundation | IKKb-matured DCs with tumor mRNA, TAA mRNA (gp100, tyrosinase, PRAME, MAGE-A3, IDO) and neoAg mRNA (GNAQ/GNA11Q209 or R183) (i.v.) | Uveal metastatic melanoma | NCT04335890 (I) | None | 2020 | Recruiting |
| Herlev Hospital | PSA, PAP, survivin, hTERT mRNA (i.d.) | Metastatic prostate cancer | NCT01446731 (II, randomized) | Docetaxel | 2011 | Completed [34] |
| Immunomic Therapeutics, Inc. | HCMV pp65-shLAMP or pp65-flLAMP, GM-CSF and td (both) | GBM, glioblastoma, malignant glioma, astrocytoma | NCT02465268 (II, randomized) | Temozolomide | 2016 | Recruiting |
| Memorial Sloan Kettering Cancer Center | Langerhans-type DCs with Trp2 mRNA | Melanoma | NCT01456104 (I) | None | 2011 | Active, not recruiting |
| Langerhans-type DCs with CT7, MAGE-A3, WT1 mRNA | Multiple myeloma | NCT01995708 (I) | Standard-of-care | 2014 | Active, not recruiting | |
| Oslo University Hospital | Tumor mRNA and hTERT, survivin TAA mRNA | Prostate cancer | NCT01197625 (I/II) | None | 2010 | Active, not recruiting |
| Radboud University | Tyrosinase, gp100 mRNA (i.d. and i.v.) | Melanoma | NCT02285413 (II, randomized) | Cisplatin | 2011 | Completed [35] |
| University Hospital Erlangen | Tumor mRNA | Uveal melanoma | NCT01983748 (III, randomized) | None | 2014 | Recruiting |
| University of Campinas | WT1 mRNA | Myelodysplastic syndromes, AML | NCT03083054 (I/II) | None | 2016 | Active, not recruiting |
| University of Florida | Total tumor mRNA and ex vivo expanded lymphocytes (i.v. and i.d.) | Medulloblastoma, neuroectodermal tumor | NCT01326104 (I, II) | None | 2010 | Active, not recruiting [36] |
| Total tumor mRNA, ex vivo expanded lymphocytes, GM-CSF and td | Diffuse intrinsic pontine glioma, Brain stem glioma | NCT03396575 (I) | Cyclophosphamide + fludarabine lymphodepleting conditioning or temozolomide | 2018 | Recruiting | |
| Universitair Ziekenhuis Brussel, Bart Nens | MAGE-A3, MAGE-C2, tyrosinase and gp100 mRNA, co-electroporated with TriMix (CD70, CD40L, caTLR4) mRNA | Melanoma | NCT01302496 (II, single arm) | Ipilimumab (antagonistic anti-CTLA-4) | 2011 | Completed [37–39] |
| Melanoma | NCT01676779 (II, randomized) | None | 2012 | Completed [39] | ||
| Direct injection of mRNA | ||||||
| BioNTech SE | RNA-LPX with NY-ESO-1, MAGE-A3, tyrosinase and TPTE (i.v.) | Advanced melanoma | NCT02410733 (I) | None | 2015 | Active, not recruiting [40, 41] |
| RNA-LPX with TNBC TAAs, p53 and neoAgs (warehouse) (i.v.) | TNBC | NCT02316457 (I) | None | 2016 | Active, not recruiting | |
| RNA-LPX with ovarian TAAs (i.v.) | Ovarian cancer | NCT04163094 (I) | Carboplatin and paclitaxel | 2019 | Recruiting | |
| RNA-LPX with prostate TAAs (i.v.) | Prostate cancer | NCT04382898 (I/II) | Cemiplimab (antagonistic anti-PD-1) and/or goserelin acetate | 2019 | Recruiting | |
| RNA-LPX with HPV16 antigens (i.v.) | HPV16+ and PD-L1+ HNSCC | NCT04534205 (II, randomized) | Pembrolizumab (antagonistic anti-PD-1) | 2020 | Not yet recruiting | |
| RNA-LPX with NY-ESO-1, MAGE-A3, tyrosinase and TPTE (i.v.) | Melanoma | NCT04526899 (II, randomized) | Cemiplimab | 2020 | Not yet recruiting | |
| RNA-LPX with CLDN6 (i.v.) | Solid tumors | NCT04503278 (I/II) | CLDN6-specific CAR-T cells | 2020 | Recruiting | |
| Genentech Inc., BioNTech SE | RNA-LPX with tumor neoAgs (i.v.) | Different solid cancers | NCT03289962 (I) | Atezolizumab (antagonistic anti-PD-L1) | 2017 | Recruiting |
| Melanoma | NCT03815058 (II, randomized) | Pembrolizumab | 2019 | Recruiting | ||
| Changhai Hospital; Stemirna Therapeutics | mRNA encoding neoAg (s.c.) | Esophageal squamous carcinoma, gastric-, pancreatic- and colorectal adenocarcinoma | NCT03468244 (NA) | None | 2018 | Recruiting |
| CureVac AG | Protamine-formulated mRNA (RNActive) PSA, PSMA, PSCA, STEAP1, PAP and MUC1 (i.d.) | Prostate cancer | NCT01817738 (I/II, randomized) | None | 2012 | Terminated [42–44] |
| NCT02140138 (II, randomized) | Radical prostatectomy | 2014 | Terminated (after enrollment of 35/36 patients) | |||
| eTheRNA | mRNA encoding tyrosinase, gp100, MAGE-A3, MAGE-C2, and PRAME and TriMix (CD40L, CD70 and caTLR4) mRNA (i.n.) | Melanoma | NCT03394937 (I) | None | 2018 | Recruiting [45] |
| Ludwig Institute for Cancer Research, CureVac AG, Böhringer Ingelheim | RNActive encoding NY-ESO-1, MAGE-C1, MAGE-C2, TPBG, survivin, MUC1 (i.d.) | Meatastatic NSCLC | NCT03164772 (I/II) | Durvalumab (antagonistic anti-PD-L1), Tremelimumab (antagonistic anti-CTLA-4) | 2017 | Recruiting |
| Merck Sharp & Dohme Corp. | LNP-formulated mRNA encoding different KRAS mutations (i.m.) | KRAS-mutant NSCLC, colorectal cancer, pancreatic adenocarcinoma | NCT03948763 (I) | Pembrolizumab | 2019 | Recruiting |
| ModernaTX Inc., Merck Sharp & Dohme Corp. | Lipid-formulated mRNA encoding neoAg (i.m.) | Solid tumors | NCT03313778 (I) | Pembrolizumab | 2017 | Recruiting [46] |
| Melanoma | NCT03897881 (II, randomized) | Pembrolizumab | 2019 | Recruiting | ||
| University of Florida | Lipid-formulated mRNA with tumor and LAMP-fused HCMV pp65 TAA mRNA (i.v.) | Adult glioblastoma | NCT04573140 (I) | None | 2020 | Not yet recruiting |
From ClinicalTrial.gov (keywords: cancer, mRNA, vaccine) on Nov 1, 2020 and PubMed literature search. AML acute myeloid leukemia, ca constitutively active, CLDN6 claudin-6, CTLA-4 cytotoxic T-lymphocyte-associated protein 4, GBM glioblastoma multiforme of brain, GM-CSF granulocyte-macrophage colony stimulating factor, HCMV human cytomegalovirus, HNSCC head and neck squamous cell carcinoma, HPV human papilloma virus, hTERT telomerase reverse transcriptase, i.d. intradermal, i.m. intramuscular, i.n. intranodal, i.v. intravenous, IDO indoleamine-pyrrole 2,3-dioxygenase, IKKb inhibitor of nuclear factor kappa-B kinase subunit beta, LAMP lysosome-associated membrane glycoprotein, MAGE melanoma-associated antigen, MUC1 mucin-1, neoAg neoantigen, NY-ESO-1 New York esophageal squamous cell carcinoma-1, NSCLC non-small-cell lung cancer, PAP prostatic acid phosphatase, PD-1 programmed cell death protein 1, PD-L1 Programmed cell death ligand 1, PRAME melanoma antigen preferentially expressed in tumors, PSA prostate-specific antigen, PSCA prostate stem cell antigen, PSMA prostate-specific membrane antigen, RCC renal cell carcinoma, RNActive Protamine-formulated mRNA, RNA-LPX liposome-formulated mRNA, s.c. subcutanous, STEAP 6-transmembrane epithelial antigen of prostate, TAA tumor-associated antigen, td tetanus-diphtheria toxoid, TLR toll-like receptor, TNBC triple-negative breast cancer, TPBG trophoblast glycoprotein, TPTE transmembrane phosphatase with tensin homology, Trp2 tyrosinase-related protein-2, WT1 Wilm’s tumor protein 1