Table 2.
Selected ongoing clinical trials of therapeutic cancer vaccines
| Clinical trial | Target antigen | Platform | Adjuvant | Dose and schedule | Indication | Combination therapy | Administration route | Primary Endpoint | Enrollment | Investigators | Start year |
|---|---|---|---|---|---|---|---|---|---|---|---|
| mRNA cancer vaccine | |||||||||||
|
(phase 3) |
Neoantigen mRNA | LNP | / | 1000 μg,9 doses, q3w | High-risk melanoma | Pembrolizumab | Intramuscular injection | RFS | 1089 |
Merck Sharp & Dohme LLC, ModernaTX, Inc. |
2023 |
|
(phase 1b/2a) |
Neoantigen mRNA | Autologous DC | / | 4 priming followed by 3 boosters | Incurable lung cancer | Pembrolizumab or durvalumab | Not mentioned | DLT, AE | 40 | Chinese Academy of Medical Sciences | 2023 |
|
(phase 1) |
Neoantigen mRNA | Lipopolyplex | / | 50–150 μg, q3w | Multiple solid tumors | / | Subcutaneous injection | DLT | 30 | Stemirna Therapeutics | 2022 |
|
(phase 2) |
Neoantigen mRNA | LNP | / | qw, q8w, up to 12 months | Resected Stage II (High Risk) and Stage III Colorectal Cancer | Pembrolizumab | Intravenous injection | DFS | 201 | BioNTech SE | 2020 |
|
(phase 2) |
Neoantigen mRNA | LNP | / | qw, q8w, up to 12 months | Advanced melanoma | Pembrolizumab | Intravenous injection | PFS | 131 | BioNTech SE | 2019 |
|
(phase 1/2)114 |
Neoantigen mRNA | LNP | / | 0.13 mg,0.39 mg, W0, W2, W4, W8, | Multiple solid tumors | Intramuscular injection | ORR, AE | 15 | BioNTech RNA Pharmaceuticals GmbH | 2018 | |
|
(phase 1/2)232 |
Neoantigen samRNA | Venezuelan equine encephalitis virus | / |
ChAdV prime 1 × 10^12 vp SAM boosts 30–300 mg |
NSCLC, gastroesophageal adenocarcinoma, urothelial carcinoma |
Nivolumab Ipilimumab |
Intramuscular injection | AE, ORR, RP2D | 29 | Gritstone bio, Inc. | 2018 |
|
(phase 1) |
Neoantigen mRNA | LNP | / | q3w | Locally advanced or metastatic tumors | Atezolizumab | Intravenous injection | DLT, AE, RP2D | 272 |
Genentech, Inc., BioNTech SE |
2017 |
|
(phase 1) |
Neoantigen mRNA | LNP | / | 40–1000 μg, 9 doses, q3w | Unresectable Solid Tumors | Pembrolizumab | Intramuscular injection | AE | 108 |
ModernaTX, Inc., Merck Sharp & Dohme LLC |
2017 |
|
(phase 2) |
HPV 16 E6 and E7 mRNA | LNP | / | Not mentioned | HPV16+ Head and Neck Cancer | Pembrolizumab | Intravenous injection | AE, OS, ORR | 285 | BioNTech SE | 2021 |
|
(phase 1/2) |
KLK-2, KLK-3, PAP, HOXB13, and NKX3.1. | LNP | / | Not mentioned | Prostate cancer | Cemiplimab | Intravenous injection | DLT, ORR | 115 | BioNTech SE | 2020 |
|
(phase 1) |
KRAS | LNP | / | 9 doses, q3w | Metastasis NSCLC, Colorectal cancer and PDAC | Pembrolizumab | Intramuscular injection | DLT, AE | 70 | Merck Sharp & Dohme LLC | 2019 |
|
(phase 1/2) |
MUC1, surviving, NY-ESO-1, 5T4, MAGE-C2, MAGE-C1 | CVCM | / | 80 μg, 12doses, | NSCLC | Durvalumab | Intradermal injection | AE | 61 | Ludwig Institute for Cancer Research | 2017 |
|
(phase 1)22 |
NY-ESO-1, MAGE-A3 and TPTE | LNP | / | 7.2–400 μg, 7 doses, q3w | Advanced melanoma | PD-1 inhibitor | Intravenous injection | AE, ORR, DCR, DoR, PFS, OS | 119 | BioNTech SE | 2015 |
|
(phase 2)233 |
MAGE-A3, MAGE-C2, tyrosinase and gp100 | autologous DC | CD70, CD40 ligand, TLR4 | 24 million DCs,4 doses, q3w | Advanced melanoma | Ipilimumab | Intradermal and intravenous injection | ORR | 39 | Bart Neyns | 2011 |
| DNA vaccine | |||||||||||
|
(phase 1) |
Neoantigen DNA | TDS-IM v2.0 | / | 6 doses, q3w followed with booster q3m | Recurrent brain tumor | / | Intramuscular injection+ electroporation | Safety and tolerability | 10 | Washington University School of Medicine | 2023 |
|
(phase 1) |
Neoantigen DNA | TDS-IM | / | 8 doses, q4w | Glioblastoma | Retifanlimab | Intramuscular injection+ electroporation | DLT | 12 | Washington University School of Medicine | 2023 |
|
(phase 1/2a) |
Neoantigen DNA | Not mentioned | Plasmid Encoded IL-12 | Not mentioned | Advanced Hepatocellular Carcinoma | Pembrolizumab | CELLECTRA®2000 EP Device | AE, immune response | 36 | Geneos Therapeutics | 2020 |
|
(phase 1) |
Neoantigen DNA | Not mentioned | Mesothelin epitope | W1, W5, W9, W13, W17, W21 | Resected pancreatic cancer | / | Intramuscular injection | AE | 15 | Washington University School of Medicine | 2018 |
|
(phase 1/2a) |
Neoantigen DNA plasmid | injection DNA plasmid pUMVC4a vector | Bempegaldesleukin | 3 mg, 14doses, q4w until week 50 | Melanoma, NSCLC, RCC, UC, SCCHN | / | Intramuscular injection | AE, immune response, ORR, DoR, PFS | 41 | Nykode Therapeutics ASA | 2018 |
|
(phase 1) |
Neoantigen DNA | TDS-IM | / | D1, 29, 57, 85 and D141 | TNBC | Durvalumab | Intramuscular injection+ electroporation | AE, immune response | 18 | Washington University School of Medicine | 2017 |
|
(phase 2) |
OncoMimics™ peptides, UCP2 | Not mentioned | Montanide | Not mentioned | Colorectal cancer | Nivolumab | Not mentioned | ctDNA response | 34 | Enterome | 2023 |
|
(phase 2) |
HPV16/18 E6/E7 | Gx-17 | Flt3L | 2 mg, 1st day of week 1,2,4 | HPV-positive head and neck cancer | Pembrolizumab | Intramuscular injection + electroporation | MPR | 25 | Yonsei University | 2022 |
|
(phase 2) |
MDM2, YB1, SOX2, CDC25B, CD105 plasmid | Not mentioned | GM-CSF | 3 doses qm + 1 dose q3m | Early stage TNBC | / | Intradermal injection | Immune response | 33 | University of Washington | 2022 |
|
(early phase 1) |
Emm55 streptococcal antigen plasmid | Not mentioned | / | 0.1 mg | Unresectable melanoma | / | Intratumoral injection | SAE, DLT | 7 | Morphogenesis, Inc. | 2018 |
|
(phase 1) |
AR LBD | Not mentioned | GM-CSF | 100 μg, 6 doses q2w followed with 4 doses q3m | Metastatic prostate cancer | / | Intradermal injection | AE, immune response | 40 | University of Wisconsin, Madison | 2015 |
|
(phase 1b/2)234 |
HPV16/18 E6/E7 | Not mentioned | Plasmid Encoded IL-12 | 4 doses, q3w | HPV-Associated Head and Neck Cancer | Stand of care | Intramuscular injection + electroporation | AE | 22 | Inovio Pharmaceuticals | 2014 |
|
(phase 1) |
Neoantigen peptides | Not mentioned | GM-CSF | D1,4,8,15, first cycle; d1 q3w | Advanced solid tumors | Pembrolizumab, | Intravenous injection | AE | 36 | Mayo Clinic | 2022 |
|
(phase 1) |
Personalized multi-peptides | Not mentioned | Poly-ICLC, CDX-301 | Not mentioned | Prostate cancer | / | Intracutaneous injection | AE | 27 | Ashutosh Kumar Tewari | 2022 |
| Peptide vaccine | |||||||||||
|
(phase 1)235 |
Neoantigen peptides | Not mentioned | GM-CSF | 100 μg, D1, D4, 8, 15, 22, 78 and 162 | Advanced pancreatic cancer | Radiofrequency ablation | Subcutaneous injection | ORR, AE | 7 | Zhejiang Provincial People’s Hospital | 2018 |
|
(phase 1b)175 |
Neoantigen peptides | Not mentioned | Poly-ICLC | 450 μg, W12D1, W12D4, W13, W14, W15, W19, W23 | NSCLC | Chemotherapy and anti-PD-1 | Subcutaneous injection | Safety and tolerability | 38 | BioNTech US Inc. | 2017 |
|
(phase 1)136 |
Neoantigen peptides | Autologous peptide | GM-CSF | W0, 1, 2, 4, 6, 8 | Advanced lung cancer | / | Subcutaneous injection | AE, ORR | 20 | Sichuan University | 2016 |
|
(phase 1b)97 |
Neoantigen peptide | Not mentioned | Poly-ICLC | 450 μg, W12D1, W12D4, W13, W14, W15, W19, W23 | Melanoma, lung cancer and bladder cancer | Nivolumab | Subcutaneous injection | Safety and tolerability | 34 | BioNTech US Inc. | 2016 |
|
(phase 1) |
DNAJB1-PRKACA fusion transcript-based peptid | Montanide ISA 51 VG | XS15 | 2 doses, q4w followed with 1 dose after 1 year | Fibrolamellar hepatocellular carcinoma | Atezolizumab | Subcutaneous injection | Immunogenicity and AE | 20 | University Hospital Tuebingen | 2023 |
|
(phase 1b) |
P30-linked EphA2, CMV pp65, and survivin peptides | Not mentioned | Poly-ICLC |
200–400 μg, 5 doses priming, d1-d22 followed with 2 doses booster d84, d140 |
Glioblastoma | Radiation therapy and temozolomide | Not mentioned | DLT | 36 | Duke University | 2023 |
|
(phase 1) |
IDH1 peptide | Not mentioned | / | 12 doses, d1, d15, d1 q4w | Recurrent IDH1 mutant lower grade glioma | Vorasidenib | Intracutaneous injection | Safety and efficacy | 48 | Duke University | 2023 |
|
(phase 2/3) |
Heat shock protein gp96-peptide | Not mentioned | / | 25 μg,8 doses, qw | Liver cancer | / | Subcutaneous injection | RFS | 80 | Cure&Sure Biotech Co., LTD | 2019 |
|
(phase 1) |
Survivin long peptide | Not mentioned | GM-CSF, IFA | 4 doses, q2w followed with q3m up to a year | Metastatic neuroendocrine tumor | Octreotide Acetate | Subcutaneous injection | AE | 14 | Roswell Park Cancer Institute | 2019 |
|
(phase 1)236 |
H3.3.K27M epitope peptide | Montanide® ISA-51 VG | poly-ICLC | 8 doses, q3w | diffuse midline glioma | Nivolumab | Subcutaneous injection | AE, OS | 50 | University of California | 2016 |
|
(phase 1)237 |
Mutated IDH1 peptide | Not mentioned | imiquimod | 300 μg, 8 doses, q2w-q4w | Grade III-IV gliomas | / | Subcutaneous injection | RLT, immune response | 39 | National Center for Tumor Diseases, Heidelberg | 2015 |
|
(phase 2) |
PAP peptide | autologous DC | GM-CSF | W0, W2, W4 | Metastatic prostate cancer | pTVG-HP plasmid DNA vaccine | Intravenous injection | Immune response | 18 | University of Wisconsin | 2013 |
|
(phase 1)227 |
pIRS2 and BRCA3 peptide | Montanide ISA-51 VG | incomplete Freund’s adjuvant and Poly-ICLC | 100 mcg and 200 mcg, 8 doses, D1, 8, 15, 36, 57, 78 | High-risk melanoma | / | Subcutaneous and intradermal injection | AE | 15 | University of Virginia | 2013 |
|
(phase 1/2a)238 |
AIM2, HT001, TAF1B neoantigen | Montanide® ISA-51 VG | / | 100 μg, qw × 4 every 3 month | MMR-deficient colorectal cancer | / | Subcutaneous injection | Immune response, ORR, AE | 22 | Oryx GmbH & Co. KG | 2011 |
CT Clinical trial, mRNA, Message RNA, LNP Lipid nanoparticle, RFS Recurrence free survival, DC Dendritic cell, DLT Dose limiting toxicity, AE Adverse events, DFS Disease free survival, PFS Progress free survival, ORR Overall response rate, samRNA Self-amplifying RNA, RP2D Recommended phase 2 dose, OS Overall survival, KLK Kallikrein, PAP Prostatic acid phosphatase, HOXB4 Homeobox gene B4, KARS Kirsten rat sarcoma virus, NSCLC Non-small cell lung cancer, PDAC Pancreatic ductal adenocarcinoma, MUC1 Mucin 1, NY-ESO-1 New York esophageal squamous cell carcinoma-1, MAGE Melanoma-associated antigen, TPTE Transmembrane phosphatase with tensin, DCR Disease control rate, DoR Duration of response, TLR Toll like receptor, ctDNA Circulating tumor DNA, RCC Renal cell carcinoma, UC Urothelial cancer, SCCHN Squamous cell carcinoma of the head and neck, TNBC Triple negative breast cancer, HPV Human papillomavirus, UCP2 Uncoupling protein 2, Flt3L Fms-related tyrosine kinase 3 ligand, MPR Major pathological remissions, MDM2 Murine double minute 2, YB1 Y-box binding protein 1, SOX2 Sex-determining region Y-box 2, CDC25B Cell division cycle protein 25B, SAE Serious adverse event, AR LBD Androgen receptor ligand-binding domain, GM-CSF Granulocyte-macrophage colony-stimulating factor, Poly-ICLC Polyriboinosinic-polyribocytidylic acid-poly-L-lysine carboxymethylcellulose, IDH1 Isocitrate dehydrogenase 1, IFA Incomplete Freund’s adjuvant, RLT Regime limiting toxicity, BRCA Breast cancer susceptibility gene, AIM2 Absent in melanoma 2, TAF1B TATA box binding protein associated factor B, MMR Mismatch repair