Table 1.
Selected therapeutic vaccines for HPV-mediated malignancies with published, trial-based data
| Antigen delivery system category, vaccine, and PMID identifier | Phase | N | Eligibility/enrolled | Adjuvant | Other therapies | Primary and secondary clinical and other outcomes |
|---|---|---|---|---|---|---|
| Small nucleic acids | ||||||
| GX-188E ([DNA plasmid encoding HPV16 and 18 E6/E7 fusion protein] + FLT3L [Fms-like tyrosine kinase-3 ligand]) | ||||||
| 33271094 [65] | II | 36 | A/R, inoperable HPV16/HPV18 + CC | EP, FLT3L | Concurrent pembrolizumab | At 24 weeks, ORR: 42% (95% CI: 23–63); CRR: 15%, PRR: 27%; median follow-up 6.2 months (IQR: 3.5–8.1 months) |
| MEDI0457/INO-3112 (VGX-3100 [DNA plasmid encoding HPV16 and 18 E6/E7 genes] with electroporation + INO-9012 [DNA plasmid encoding IL-12]) | ||||||
| 32151670 [68] | I | 10 | Persistent/recurrent cervical cancer after CRT | EP, IL-12 | - | Any treatment-related AEs were grade 1; 8/10 patients with detectable cellular or humoral immune responses against HPV antigens |
| Bacterial vector | ||||||
| ADXS11-001 (ADXS-HPV; axalimogene filolisbac [AXAL]; Lm-LLO-E7; live attenuated Listeria monocytogenes encoding HPV 16 E7 and tLLO) | ||||||
| 29538258 [66] | II | 109 | Recurrent/refractory cervical cancer following prior chemotherapy and/or radiotherapy | tLLO | ADXS11-001 alone or with cisplatin | Median OS: ADXS11-001: 8.3 months; 95% CI, 5.9–10.5 months; ADXS11-001 + cisplatin: 8.8 months; 95% CI, 7.4–13.3 months. Best ORR: ADXS11-001 alone: 17%; ADXS11-001 + cisplatin: 15% |
| 29722659 [72] | I | 10 | Untreated, invasive, anal canal SCC | tLLO | ADXS11-001 administered as neoadjuvant and adjuvant therapy with concurrent chemoradiation | CRR: 100% among 9 patients completing treatment; rate of grade 3 AEs associated with ADXS11-01: 22% |
| 32341753 [67] | II | 36 | R/M anorectal SCC not amenable to curative surgery | tLLO | - | ORR: 3.4%; rate of stable disease: 20.7%; 6-month PFS: 15.5%; median PFS: 2.0 months; OS: 12.6 months; rate of grade 3 AEs: 28%; rate of grade 4 AEs: 3% |
| 32641240 [69] | II | 50 | Metastatic CC s/p curative treatment + ≥ 1-line(s) of systemic chemotherapy and/or biologic therapy | tLLO | - | Any AEs: 98%; rate of grade 3 AEs: 38%; grade 4 AEs: 4% (lung infection/sepsis; hypotension/cytokine release); OS at 12-months: 38%; median OS 6.1 months (95% CI: 4.3–12.1 months); medians PFS 2.8 months; 2% PRR, 10% stable disease |
| Peptides | ||||||
| ISA101 (HPV16 E6/E7-SLPs [nine E6 SLPs, four E7 SLPs) | ||||||
| 23557172 [74] | II | 20 | Incurable R/M HPV16 + gynecologic cancers (16 CCs, 2 VaCs, 2 ACs) | Montanide® ISA-51 | - | ORR: 0%; median OS: 12.6 months; immune response identified in 11/13 patients |
| 30267032 [70] | II | 24 | Incurable HPV16 + cancers (22 OPCs, 1 CC, 1 AC) | - | Concurrent nivolumab | ORR: 33% (90% CI: 19–50%); CRR: 8%, PRR: 25%; median duration of response: 10.3 months; median PFS: 2.7 months; median OS: 17.5 months |
| 35193933 [73] | “ | “ | (Longer-term data of the above trial) | “ | “ | ORR: 29%; median OS of 15.3 months and 2-year OS rate of 33%. Higher expression of immune, inflammatory, and interferon-signaling pathway genes were correlated with clinical response |
| P16-37–63 (p16INK4a 27-amino acid peptide fragment) | ||||||
| 26949913 [71] | I/IIa | 26 | A/R HPV + cancers (17 CCs, 7 OPCs, 1 VuC, 1 AC) | Montanide® ISA-51 VG | - | Patients experienced grade I AEs only (CTCAE); immune response identified in 17/20 patients; ORR: 0% median follow-up 5.6 months; median PFS 3.5 months, median OS 11.9 months |
| GL-0810 (HPV16 E7 peptides linked to a “penetrin” peptide sequence facilitating translocation to the ER + GA [Trojan peptide-based vaccine]) | ||||||
| 25537079 [75] | I | 9 | R/M HPV16 + HNSCC | Montanide® ISA-51 VG + GM-CSF | Grade 1 toxicity: 7/9; grade 2 toxicity: 3/9; T cell and antibody response in 4/9 patients [4/5 who received all 4 vaccinations; ORR: 0%; PFS: 80 days; OS: 196 days | |
| Autologous cell-based | ||||||
| BVAC-C (autologous B cells and monocytes transfected with recombinant HPV16/18 E6 and E7 genes) | ||||||
| 31948126 [76] | I | 11 | R/M HPV16/18 cervical cancer | α-Galactosyl ceramide | - | ORR: 11% (95% CI: 0–32%); 56% achieved stable disease (95% CI: 23–88%); median OS: 12 months |
A advanced, AE adverse event, CC cervical cancer, CI confidence interval, CR complete response, CTCAE Common Terminology Criteria for Adverse Events, ER endoplasmic reticulum, GA Golgi apparatus, GM-CSF granulocyte–macrophage colony-stimulating factor, HNSCC head and neck squamous cell carcinoma, IQR interquartile range, ORR overall response rate OS overall survival, PRR partial response rate, R/M recurrent/metastatic, SCC squamous cell carcinoma