Table 4.
Advances in clinical trials for personalized neoantigen-based cancer vaccines
| Vaccine type | Clinical trial number | Phase | Name | Characteristic | Administration route | Doses | Combination therapy | Enrollment | Primary clinical outcome |
| Peptide | NCT01970358 | I | NeoVax | Personalized neoantigen Immunizing long peptides (IMP), 13–20 neoantigen peptides in 4 pools |
s.c. | 0.3 mg per peptide | - | 6 | Melanoma (n = 6): stage IIIB/C: 4/4 without disease recurrence; IVM1a/b: 2/2 PD after vaccine treatment, subsequently treated with anti-PD-1 therapy to CR59. |
| Peptide | NCT02287428 | I/Ib | NeoVax | Personalized neoantigen up to 20 IMP in 3–5 pool | s.c. | 0.3 mg per peptide | - | 3 | Glioblastoma (n = 3): 3/3 patients required dexamethasone during vaccine priming failed to generate interferon-γ (IFNγ) responses, median PFS was 7.6 months (90% confidence interval, 6.2–9.5), and median OS was 16.8 months (90% confidence interval, 9.6–21.3)58. |
| Peptide | NCT03645148 | I | iNeo-Vac-P01 | Personalized neoantigen long peptides (15-35aa) 5–20 neoantigen peptides in 2∼4 pools | s.c. | 0.1 mg per peptide | Chemotherapy | 7 | Pancreatic cancer (n = 7): 2/7 PR, 4/7 SD, and 1/7 PD, mean OS was 24.1 months (11–31.4 months), and the mean PFS was 3.1 months82. |
| Peptide | NCT03662815 | I | iNeo-Vac-P01 | Personalized neoantigen long peptides (15-35aa) 5–20 neoantigen peptides in 3∼4 pools | s.c. | 0.1 mg or 0.3 mg per peptide | RFA | 25 | All patients (colon cancer, melanoma, lung cancer, pancreatic cancer, biliary tract cancer) (n = 25). RFA+Vac (n = 9): 1/9 PR, 7/9 SD, 1/9 PD; Vac (n = 11): 11/16 SD, 5/16 PD; RFA+Vac vs. Vac: median PFS was 4.42 vs. 2.82 months, median OS was 20.8 vs. 10.94 months. Colon cancer: RFA+Vac vs. RFA: median OS was 21.27 vs. 11.55 months83. |
| Peptide | NCT02897765 | I | NEO-PV-01 | Personalized neoantigen Long peptides (14-35aa), up to 20 neoantigen peptides in 4 pools |
s.c. | 0.3 mg per peptide | Anti-PD-1 | 60 | Melanoma (n = 27): 1/27 CR, 15/27 PR, 7/27 SD, and 4/27 PD, mean OS was not reachedd, and the mean PFS was 23.5 months. NSCLC (n = 18): 7/18 PR, 9/18 SD, and 2/18 PD, mean OS was not reached, and the mean PFS was 8.5 months. |
| Bladder cancer (n = 15): 1/15 CR, 3/15 PR, 9/15 SD, and 2/15 PD, mean OS was 20.7 months, and the mean PFS was 5.8 months84. | |||||||||
| Peptide | NCT03380871 | Ib | NEO-PV-01 | Personalized neoantigen long peptides (14-35aa), up to 20 neoantigen peptides into 4 pools |
s.c. | 0.3 mg per peptide | Chemotherapy+anti-PD-1 | 15 | NSCLC (n = 15): Vac group: Mean OS was 20 months, and the mean PFS was 7.2 months Anti-PD-1 (without Vac): Mean OS was 16.8 months, and the mean PFS was 6.3 months85 |
| Peptide | NCT03715985 | I/II | EVX-01 | Personalized neoantigen; ong peptides (15-27aa), 5–10 neoantigen peptides | i.m. | Total 0.5 mg per dose | Anti-PD-1 | 5 | Melanoma (n = 5): 1/5 CR, 2/5 PR, 2/5 PD Mean OS was not reached, and the mean PFS was 23.5 months86 |
| Peptide | NCT02149225 | I | GAPVAC-101 | Shared neoantigen + Personalized neoantigen | i.d | 400 μg per peptide | - | 15 | Glioblastoma (n = 15): Mean OS was 29 months, and the mean PFS was 14.2 months87. |
| Peptide | ChiCTR1900020990 | I | - | Personalized neoantigen long peptides (27aa), 6–20 neoantigen peptides into 1–4 pools |
s.c | - | - | 10 | HCC with the high risk of recurrence (n = 10): 8/10 patients were confirmed with clinical relapse by imaging, the other 2 patients remained relapse-free. The median RFS was 7.4 months88 |
| Peptide-pulsed DC | NCT02956551 | I | Neo-DCVac | Personalized neoantigen, DCs pulsed with 1–5 neoantigen peptides |
s.c. | Median number of viable cells per dose: 1.60 × 107 | - | 12 | Relapsed advanced lung cancer (n = 12): 3/12 PR, 3/12 SD, and 6/12 PD, median OS was 7.9 months, and the median PFS was 5.5 months89 |
| Peptide-pulsed DC | NCT03185429 | I | Neo-MoDC | Personalized neoantigen, DCs pulsed with 8 neoantigen peptides | s.c. | 2.0 × 107–4.0 × 107 DCs per dose | Nivolumab | 1 | Metastatic gastric cancer (n = 1): 1/1 CR90 |
| mRNA | NCT02035956 | I | - | Two synthetic pharmacologically optimized RNA molecules per patient, each with 5 mutations (pentatope RNA) |
Ultrasound-guided percutaneous vaccine injection into lymph nodes | 0.5 mg or 1 mg per treatment | - | 5 | Stage III and IV melanoma (n = 5): Two of the five patients with metastatic disease experienced vaccine-related objective responses. A third patient developed a CR to vaccination in combination with PD-1 blockade therapy91. |
| mRNA | NCT03480152 | I | mRNA-4650 | Included any mutation in the TP53, KRAS, or PIK3CA driver genes and up to 15 in silico-predicted HLA-I potential neoantigens. | i.m. | 0.13 mg or 0.39 mg | 4 | Metastatic gastrointestinal (GI) cancer (n = 4): 4/4 no clinical response, 3/4 detected both CD8 and CD4+ neoantigen-specific T cells86. |
|
| mRNA | NCT03639714 | I | GRT-C901 GRT-R902 |
Personalized neoantigen vaccine that employs adenoviral (GRT-C901) and self-amplifying mRNA (GRT-R902) vectors | i.m. | 30 μg and 100 μg samRNA | Nivolumab | 13 | Advanced metastatic solid tumors (n = 13): NSCLC (n = 1): 1/1 PD; GEA (n = 5): 1/5 CR, 3/5 PD, 1/5 SD; MSS-CRC (n = 7): 7/7 PD, Median OS 8.7 months92 |
HCC, hepatocellular carcinoma; NSCLC, non-small cell lung cancer; GEA, gastroesophageal adenocarcinoma; MSS-CRC, microsatellite stable colorectal cancers; IFN-γ, interferon-γ; PD-1, programmed death-1; RFA, radiofrequency ablation; Vac, vaccine; IMP, immunizing long peptides; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; PFS, progressive disease; OS, overall survival; DC, dendritic cell; mRNA, messenger ribonucleic acid; samRNA, self-amplifying mRNA; i.d., intradermal; i.m., intramuscularly; s.c., subcutaneous; μg, microgram.