Clinical trials with TAA and neoantigens-based cancer vaccines encoding

Organ Cancer type/stage Phases Cancer vaccine TAA/neoantigens Formulation Study results Sponsor NCT number Reference
Lung NSCLC
Stage IIIB or IV
Phase IIB trial TG4010 MUC1 TG4010: recombinant modified vaccinia virus strain Ankara (MVA) encoding MUC1 and human interleukin 2 (IL-2) TG4010 enhances the effect of chemotherapy in advanced NSCLC patients Transgene SA (France) NCT00415818 [50]
Lung NSCLC
Stage IIIA vs. IIIB
START study: phase III trial Stimuvax MUC1 Tecemotide: MUC1-derived 25-amino acid BLP25 lipopeptide, immunoadjuvant monophosphoryl lipid A, and three liposome-forming lipids No significant difference in overall survival for all patients Merck KgaA (Germany) NCT00409188 [49]
Lung NSCLC
Stage IB, II and IIIA
Phase III trial MAGE-A3 (AS15 and AS02B) MAGE-A3 Adjuvant treatment with MAGE-A3 MAGE-A3 immunotherapeutic use in NSCLC has been stopped GlaxoSmithKline (GSK) Biologicals SA (UK) NCT00480025 [47]
Lung NSCLC
Stage IB to IIIA
Phase I dose escalation PRAME (with AS15) PRAME PRAME recombinant protein with AS15 Anti-PRAME humoral responses with no cancer regression stopped due to negative results GSK Biologicals SA (UK) NCT01159964 [48]
Lung NSCLC
Stage IIIB/IV
Phase II trial Personalized peptide vaccine with docetaxel Several TAA 31 Peptides from several TAA Positive predictive value (PPV) may be efficacious for the humoral immunological responders but did not improve survival in combination with docetaxel for NSCLC patients Kurume University Research Center for Innovative Cancer Therapy Kurume University School of Medicine (Japan) UMIN Clinical Trials Registry (UMIN number 000003521) [53]
Skin Melanoma
Stage IIIA-C/IV
Phase I trial IVAC mutanome Multiple neoantigens Poly-neo-epitopic coding RNA vaccine Immune responses to the majority of neoantigens contained in the vaccine/vaccine-induced T-cell responses in all vaccinated melanoma patients BioNTech RNA Pharmaceuticals GmbH (Germany) NCT02035956 [37]
Lung NSCLC
Stage IV
TIME study: phase IIB/III trial TG4010 MUC1 TG4010: recombinant MVA encoding MUC1 and human IL-2 TG4010 modulates CD8+ T-cell response with improvements in clinical outcome Not applicable NCT01383148 [52]
Brain Glioblastoma
Stage IV
Phase I trial Actively personalized vaccine 1 (APVAC1) 7 Non-mutated peptides, 1 viral peptide, and 2 tumor-associated peptides APVAC1 vaccine plus poly-ICLC (Hiltonol®) and GM-CSF Unmutated APVAC1 antigens elicited sustained responses of central memory CD8+ T cells Immatics Biotechnologies GmbH (Germany) NCT02149225 [56]
Brain Glioblastoma
Stage IV
Phase I trial Glioblastoma personalized peptide vaccine (GBM PVax) 8 Synthetic long peptides targeting seven neoantigens Personalized neoantigen-based long peptide vaccine with poly-ICLC (Hiltonol®) Specific T-cell responses in the blood Washington University School of Medicine (USA) NCT02510950 [57]
Brain Glioblastoma
Stage IV
Phase I/IB trial Personalized neoantigen targeting vaccine 20 Long peptides divided into pools of 3–5 peptides admixed with poly-ICLC Neoantigen vaccine with radiation therapy plus pembrolizumab Polyfunctional neoantigen-specific CD4+ and CD8+ T-cell responses exhibiting memory phenotype Dana-Farber Cancer Institute (USA) NCT02287428 [58]
Lung NSCLC
Stage IV
Phase II trial Tedopi® 5 TAA (CEA, p53, HER2/neu, MAGE2 and MAGE3) Tedopi plus docetaxel or tedopi plus nivolumab T-cell response with a better survival rate OSE Immunotherapeutics (France) NCT04884282 [54]
Digestive system Gastrointestinal
Stage IV
Phase I/II trial mRNA-4650 Up to 20 different neoantigens Neoantigen mRNA-based cancer vaccine mRNA-4650 vaccine was safe and elicited mutation-specific T-cell responses against predicted neoepitopes National Cancer Institute (USA) NCT03480152 [59]
Skin Melanoma
Stage IIIB, C, and IV
Phase I (Lipo-MERIT trial) FixVac (BNT 111) 4 TAA (NY-ESO-1, MAGE-A3, tyrosinase, and TPTE) Liposomal RNA (RNA-LPX) vaccine Strong CD4+ and CD8+ T-cell immunity against the vaccine antigens/antigen-specific cytotoxic T-cell responses in some responders reach magnitudes and are durable BioNTech SE (Germany) NCT02410733 [40]
Lung Advanced lung cancer
Stage IV
Phase I trial Neo-DCVac 13–30 Peptide-based neoantigens Neoantigen-pulsed DC vaccine Neo-DCVac was well tolerated, safe, and capable of eliciting specific T-cell immunity and therapeutic benefit Sichuan University (China) NCT02956551 and Chinese Clinical Trial Registry (ChiCTRONC-16009100) [60]
Skin Melanoma
Stage IIIB/C and IVM1a/b
Phase I trial NeoVax Long-peptide vaccine targeting up to 20 personal neoantigens Neoantigen vaccine with poly-ICLC (Hiltonol®) T-cell responses with ex vivo detection of neoantigen-specific T cells exhibiting memory phenotype Patrick Ott, MD (USA) NCT01970358 [61]
Brain Glioma
Stage III/IV
Phase I trial Isocitrate dehydrogenase type 1 (IDH1)-vac 20-Mer peptide-based neoantigens encompassing IDH1R132H-mutated region IDH1 peptide vaccine with Montanide® IDH1 was immunogenic and induces specific T helper cell responses National Center for Tumor Diseases (Germany) NCT02454634 [62]
Pancreas Pancreatic carcinoma
Stage IV
Phase I trial iNeo-Vac-P01 5–20 Peptides-based neoantigens Neoantigen-based peptide vaccine (iNeo-Vac-P01) with adjuvant (GM-CSF) No severe vaccine-related adverse effects/higher peripheral IFN-γ titer and CD4+ or CD8+ effector memory T cells count post-vaccination Zhejiang Provincial People’s Hospital (China) NCT03645148 [63]

GM-CSF: granulocyte-macrophage colony-stimulating factor; IFN-γ: interferon-γ