Table 1.
Published and presented clinical trials of self-replicating RNA cancer vaccines.
| Ref NCT # phase name of vaccine | Based on RNA virus | VRP or LNP | Antigen | Doses administered | Number of patients treated | Toxicities | Tumor antigen specific immune response | Clinical response/outcomes |
|---|---|---|---|---|---|---|---|---|
|
6 Phase I VRP-CEA(6D) |
VEE | VRP | CEA |
4 × 107 IU per 0.5 ml and 4 × 108 IU per 0.5 mL IM. Doses every 3 weeks for 4 immunizations. Additional boosters allowed if stable. |
28 M:18, F:10. CRC: 23 NSCLC: 2 Panc: 1 Append: 1 Breast: 1 |
No grade 3,4 toxicity attributed to vaccine. 2 with grade 1 injection site pain | T and B cell |
1 CR, 2 SD 2 with NED remained without progression. Better survival with an immune response by ELISpot |
|
9 NCT # not listed Phase I PSMA-VRP |
VEE | VRP | PSMA |
1.8 × 107 and 0.72 × 108 IU/mL SC. Doses at weeks 1, 4, 7, 10, and 18 |
12 M:12 Metastatic CRPC: 12 |
No grade 3,4 adverse events attributable to vaccine; Gr 1/2 fatigue in 8 patients |
B cell | Two patients from each dose level showed marked reduction in the N-telopeptide levels (marker of bone turnover) |
|
10 Phase I VRP-HER2 |
VEE | VRP | HER2 |
5.2 × 108 IU/mL IM. Doses every 2 weeks for 3 doses. |
22 M:1 F: 21 Median age 58.5 (range 53–64) Breast: 21 Esoph: 1 |
No grade 3,4 adverse reactions 2 Grade 1 injection site reactions |
T and B cell | 1 PR/2 SD. mOS 50.2 mo in cohort 1; 32.7 mo in cohort 2. Perforin expression by memory CD8 T cells post-vaccination significantly correlated with improved PFS. |
|
7 Pilot VRP-CEA(6D) |
VEE | VRP | CEA |
4 × 108 IU per 0.5 mL IM Doses every 3 weeks × 4 doses |
12 M:4 F:8 Median age 53 (IQR 43–62) All CRC stage III |
No grade 3,4 adverse events. 3 grade 1 injection site reactions, 2 grade 1 fever |
T and B cell | 5-year RFS was 75%, (95%CI 40–91%); |
|
11 NCT # not listed Phase I Vvax001 |
SFV | VRP | HPV E6, E7 |
1.25 × 108 IP/mL IM Doses every 3 weeks × 3 doses. Each dose was given as two injections, one IM in 1 mL in each upper leg |
12 F: 12 HPV-induced CIN 2 or 3 |
Mild injection site reaction, injection site hematoma, peripheral edema, chills, myalgia, back pain, and lymphadenopathy | T cell | NR |
|
16 NCT03639714 Phase I GRT-C901/ GRT-R902 |
Prime: ChAd Boost: self amplify-ing RNA | LNP | Individualized neoepitopes | IM Dose not listed + 30 mg SC ipilimumab and 480 mg IV nivolumab |
26 (18 evaluable) (NSCLC, CRC, gastro-esoph, urothelial) |
Injection site reactions and fever | T cell (and B cell) | 1 CR, 4 SD, 11 PD, and 2 no measurable disease. 4/5 had decrease in ctDNA |
|
17 NCT03953235 Phase I GRT-C903/ GRT-R904 |
Prime: ChAd Boost: self amplify-ing RNA | LNP | Shared neoepitopes (of KRAS, NRAS, BRAF and others) | IM Dose not listed + 30 mg SC ipilimumab and 480 mg IV nivolumab |
26 (NSCLC, CRC, pancreatic cancer, and others with shared epitopes) |
Injection site reactions and fever | Not reported | 66% of NSCLC patients had decrease in ctDNA |
ChAd Chimpanzee Adenovirus, SFV Semliki Forest Virus, VEE Venezuelan Equine Encephalitis, IP infectious particles, SC subcutaneous, IV intravenous, IM intramuscular, CRC colorectal, NSCLC non-small cell lung cancer, CRPC castrate resistant prostate cancer, CIN cervical intraepithelial neoplasia.