Table 1.
Major clinical trials of colorectal cancer vaccines.
| Interventions | Adjuvant/ combined therapy | Stage | Design and arms | Primary objective | Results | Phases | NCT Number/ Reference | |
|---|---|---|---|---|---|---|---|---|
| Moleculer-based vaccine | HLA-A*2402-restricted peptides | mFOLFOX6 or XELOX | advanced CRC | Single arm: HLA-A*2402 restricted peptides + chemotherapy (N=96) | RR, PFS, OS | No significance was observed for planned statistical efficacy endpoints. | II | (32) |
| Five HLA-A*2402-restricted peptides | Cyclophosphamide | advanced CRC | Single arm: Five HLA-A*2402-restricted peptides + chemotherapy (N=9) | Safety, immune response | The vaccine was safe. Induced T-cell responses were observed. | I | (33) | |
| mRNA 4157 | Pembrolizumab | mCRC | Arm 1: Vaccine at different doses Arm 2: Vaccine + chemotherapy |
Safety, immune response | A portion of results showed that this vaccine was safe, well-tolerated and could induce strong neoantigen-specific T cell responses. | I | NCT03313778 (34) | |
| V 941 (mRNA 5671) | Pembrolizumab | KRAS positive cancers | Arm 1: Vaccine alone Arm 2: Vaccine + chemotherapy |
Safety, immune response, ORR | The clinical trial is underway and the results are eagerly awaited. | I | NCT03948763 | |
| Cancer cell vaccines | OncoVax | Bacillus Calmette-Guerin (BCG) | Stage II (N=297) , Stage III (N=115) | Treatment arm: Surgery + vaccination Observation arm: Surgery alone |
OS, DFS | Trend toward better DFS (p = 0.078) and OS (p = 0.12). DFS (p = 0.006) and OS (p = 0.017) improved in stage II patients. | III | (35) |
| GVAX | GM-CFS, cyclophosphamide/ Pembrolizumab | advanced pMMR CRC | Single arm: GVAX/Cy + pembrolizumab (N=17) | ORR, safety, PFS, OS, DOR | The median PFS was 82 days (95% CI 48-97days) and the median OS was 213 days (95% CI 179-441 days). Toxicities were acceptable. | II | NCT02981524 (36) | |
| GM-CSF, cyclophosphamide/ guadecitabine | advanced CRC | Single arm: GVAX/Cy (N=18) | Immune response, safety | No significant increase in CD45RO+cells was noted. Grade 3–4 toxicities were expected and manageable. | I | NCT01966289 | ||
| Dendritic cells vaccine | Dendritic cells vaccine | / | mCRC | Vaccine arm: DC vaccine (N=8), Control arm (N=7) | DFS | DFS of the vaccine arm was 25.26 months (95% CI 8.73-n.r) versus 9.53 months (95% CI 5.32-18.88) in control arm. | II | NCT01348256 (37) |
| Ex vivo TNF-α, IL1, IL6, and PGE2 | advanced CRC | Single arm: DC vaccine (N=20) | Safety, OS, RFS | Median OS 7.4 m + G3 (G3 CI, 4.5–17.5 m); median time of tumor progression, 2.4 months (95% CI 1.9–4.1 months). | I/II | (38) |
mCRC, metastatic colorectal cancer; MSS, microsatellite stable; pMMR, proficient mismatch repair; RR, response rate; PFS, progression-free survival; OS, overall survival; ORR, objective response rate; DFS, disease-free survival; DOR, duration of response; PFS, progression free survival.