Table 2 Published and registered clinical trials of repRNA vaccines against cancer
From: Replicon RNA vaccines: design, delivery, and immunogenicity in infectious diseases and cancer
Ref # Study ID number # Phase name of the vaccine | Viral vector | delivery approach | antigen | Vaccination dose regimen | Patients | Toxicities | Tumor antigen-specific immune response | Clinical response/ outcomes |
|---|---|---|---|---|---|---|---|---|
268 NCT00408590, CDR0000515008 Phase I MV-CEA | MV | VRP | CEA | 1 dose per month, overall, 6 doses. Dose levels range from 103 to 109 TCID50 per 500 ml (seven dose levels, dose escalation by 1-log increments) IV | 21 F:21 Recurrent ovarian cancer:21 | AE in cycle 1: grade 1 and 2 AE | Suboptimal antibody responses | SD:17 (dose-dependent), median duration = 92.5 days PD:4 Median overall survival = 12.15 months 3 in 109 TCID50 dose level, 2 in 108 TCID50 dose level had > 30% decrease in tumor marker CA-125 |
269 NCT00529984 Phase I VRP-CEA(6D) AVX701 | VEEV | VRP | CEA | 4 × 107 IU in 0.5 ml or 1 × 108 IU in 0.125 ml or 4 × 108 IU in 0.5 ml. 4 doses with 3-week intervals. Additional boosters were allowed if stable IM | 28 M:18, F:10. Colorectal cancer: 23, non-small cell lung cancer: 2, pancreatic cancer: 1, Appendiceal cancer: 1, breast: 1 | 2 with grade 1 injection site pain, no vaccination-related grade 3,4 AE | T cell and B cell | 1 CR, 2 SD, 2 with no evidence of disease before immunization had no progression Better survival |
270 NCT01890213 Pilot VRP- CEA(6D) AVX701 | VEEV | VRP | CEA | 4 × 108 IU per 0.5 ml 4 doses with 3-week intervals IM | 12 M:4, F:8 Colorectal cancer stage III | 3 grade 1 injection site reactions, 2 grade 1 fever | T cell and B cell | Median follow-up = 10.9 years, 5- year survival = 17%, 5- year relapse-free survival = 75%, no deaths |
272 Study ID not documented Phase I PSMA-VRP | VEEV | VRP | PSMA | 0.9 × 107 and 0.36 × 108 IU/ml 5 doses at weeks 1, 4, 7, 10, and 18 respectively SC | 12 M:12 Metastatic castrate-resistant prostate cancer: 12 | 8 grade 1/2 fatigue | B cell | Two patients from each dose level had a reduction in the N-telopeptide levels, a bone turnover marker, with a more substantial impact at 0.9 × 107 IU |
273 NCT01526473 Phase I VRP-HER2 | VEEV | VRP | HER2 | Cohort 1: 4 × 108 IU/ml. 3 doses with 2-week intervals. IM Cohort 2: 4 × 108 IU/ml. 3 doses of vaccination with 2 week intervals combined with concurrent anti-HER2 therapy. IM | 22 M:1 F: 21 Breast cancer:21 Esophageal cancer:1 | No grade 3/4 AEs were attributed to the immunization. Grade 1–2 AEs: 2 fevers, 1 fatigue, 2 injection site reactions, 1 malaise, 1 rash pustular, 7 musculoskeletal and connective tissue disorders, 1 urinary retention | T cell and B cell | 1 PR, 2 SD mOS 50.2 months in cohort 1; 32.7 months in cohort 2 Perforin expression by memory CD8 T cells significantly correlated with improved PFS |
274 NCT03632941 Phase II AVX901 | VEEV | VRP | HER2 | VRP-HER2 vaccine 4 × 108 IU given as a single injection every 2 weeks for 3 injections total | Not recruiting | Unknown | Unknown | Unknown |
275 NCT00450814 Phase I MV-NIS | MV | VRP | Human thyroidal sodium-iodide symporter (NIS) | Stage 1: 1 × 106 MV-NIS (TCID50)/ 1 × 107 MV-NIS (TCID50)/ 1 × 108 MV-NIS (TCID50)/ 1 × 109 MV-NIS (TCID50)/ 1 × 1010 MV-NIS (TCID50) / 1 × 1011 MV-NIS (TCID50) per 250 ml Stage 2: 10 mg/kg cyclophosphamide + 107 MV-NIS (TCID50)/ 3 × 107 MV-NIS (TCID50)/ 9 × 107 MV-NIS (TCID50) per 250 ml IV | 44 F:18 M:26 Relapsed or refractory myeloma: 44 | Grade 1–2 AEs: 10 nausea, 9 chills, 8 leukopenia, 7 fever, 5 diarrhea, 5 neutropenia Grade 3–4 AEs: 9 neutropenia, 5 leukocyte count decreased, 2 thrombocytopenia, 1 CD4 lymphocyte decreased, 1 anemia,1 lymphopenia, 1 left ventricular failure | T cell and B cell | 1 CR, others had transient drops in serum immunoglobulin free light chains |
276 NCT03141463 Phase I Vvax001 | SFV | VRP | HPV16-derived antigens E6 and E7 | 4 dose levels tested: 5.0 × 105, 5.0 × 106, 5.0 × 107, 2.5 × 108 infectious particles per immunization 3 doses were given at 3-week intervals IM | 12 F: 12 HPV-induced cervical intraepithelial neoplasia grade 2 or 3 | No grade 3,4 AEs Only mild myalgia and injection site reactions | T cell and B cell | Unknown |
277, 278 NCT06015854 Phase II Vvax001 | SFV | VRP | HPV16-derived antigens E6 and E7 | 5 × 107 infectious particles per immunization, 3 immunizations with 3 week intervals Bilateral IM | Cervical intraepithelial neoplasia grade 3 | No serious AEs | T cell and B cell | Reductions in HPV16-positive cervical intraepithelial neoplasia grade 3 (CIN3) lesion sizes in 17/18 patients Histopathological CR in 9/18 of patients HPV16 clearance in 10/16 of patients |