Table 2.
Selected therapeutic vaccines for HPV-mediated premalignancies and malignancies under active or completed trial-based investigation, without published results
| Antigen delivery system category and vaccine | Phase | N | Eligibility | Adjuvant | Other therapies | (Projected) trial end date |
|---|---|---|---|---|---|---|
| Small nucleic acids | ||||||
| MEDI0457/INO-3112 (VGX-3100 [DNA plasmid encoding HPV16 and 18 E6/E7 genes] with electroporation + INO-9012 [DNA plasmid encoding IL-12]) | ||||||
| NCT03439085 | II | 77 | R/M HPV16/18 + cancers | EP, IL-12# | Concurrent durvalumab | Dec 2022 |
| NCT02172911 | I/II | 10 | Primary CC s/p CRT; R/M CC | EP, IL-12# | Curative intent: INO-3112 as adjuvant; R/M: INO-3112 alone | Sept 2017 |
| NCT03162224 | I/IIa | 35 | R/M HPV + HNC | EP, IL-12# | Concurrent durvalumab | March 2021 |
| NCT02163057 | I/IIa | 22 | HPV + HNC | EP, IL-12# | INO-3112 followed by surgery vs CRT | January 2017 |
| NCT03185013 | III | 201 | HPV 16/18 + CIN2/3 | EP | VGX-3100 only | April 2021 |
| NCT03721978 | III | 203 | HPV 16/18 + CIN2/3 | EP | VGX-3100 only | Sept 2022 |
| NCT03603808 | II | 80 | HIV + patients with anal HPV16/18 + HSIL | EP | VGX-3100 only | Aug 2022 |
| NCT00685412 | I | 18 | CIN II/III patients after surgery/ablation | EP | VGX-3100 only | March 2011 |
| NCT03180684 | II | 36 | VIN 2/3 | EP | Imiquimod | December 2020 |
| GX-188E ([DNA plasmid encoding HPV16 and 18 E6/E7 fusion protein] + FLT3L [Fms-like tyrosine kinase-3 ligand]) | ||||||
| NCT03444376 | Ib/II | 60 | Advanced, unresectable HPV16/18 + CC | EP, FLT3L# | Concurrent pembrolizumab | Dec 2023 |
| NCT02596243 | III | 134 | HPV 16/18 + CIN 2/3 | EP, FLT3L# | - | Aug 2018 |
| NCT02139267 | II | 72 | HPV16/18 + CIN 3 | EP, FLT3L# | - | March 2016 |
| VB10.16 (DNA plasmid encoding recombinant protein consisting of 3 modules: inactivated HPV16 E6/E7 protein, human chemokine MIP-1α, linked via dimerization module derived from human IgG3) | ||||||
| NCT04405349 | IIa | 50 | R/M HPV16 + CC ineligible for other therapies | MIP-1α# | Concurrent atezolizumab | Jan 2023 |
| NCT02529930 | I/II | 34 | HPV16 + cervical HSIL (CIN 2/3) | MIP-1α# | - | Jan 2019 |
| pNGVL4aCRTE6E7L2/ pNGVL4aCRTE6E7(detox) (DNA plasmid encoding calreticulin, HPV16 E6/E7/L2 proteins) | ||||||
| NCT04131413 | I | 48 | HIV + HPV16 + CIN2/3 | - | - | December 2024 |
| NCT00988559 | I | 132 | HPV16 + CIN 2/3 | - | ± Imiquimod | July 2016 |
| BNT113 (mRNA encoding HPV16 E6 and E7 proteins encapsulated within liposomes) | ||||||
| NCT04131413 | II | 285 | Unresectable, R/M HPV16 +, PD-L1 + HNSCC | Liposomes | Pembrolizumab alone versus pembrolizumab with BNT113 | May 2025 |
| NCT03418480 | I/II | 44 | Previously treated HPV16 + HNSCC; advanced HPV16 + mediated cervical, head and neck, anal, or penile cancer | Liposomes | Oct 2024 | |
| Viral vector (see combination vaccine category: TA-HPV, Ad-E6E7, MG1-E6E7) | ||||||
| Bacterial vector | ||||||
| ADXS11-001 (ADXS-HPV; axalimogene filolisbac [AXAL]; Lm-LLO-E7; live attenuated Listeria monocytogenes encoding HPV 16 E7 and tLLO) | ||||||
| NCT02002182 | II | 15 | Resectable HPV + OPC | tLLO# | ADXS11-001 followed by primary surgery | Aug 2023 |
| NCT02399813 | II | 51 | Persistent/recurrent anorectal SCC s/p at least one treatment regimen | tLLO# | - | May 2019 |
| NCT02853604 | III | 450 | High-risk locally advanced CC after CRT | tLLO# | ADXS11-001 as adjuvant after definitive CRT | October 2024 |
| Peptides | ||||||
| ISA101/101b (HPV16 E6/E7-SLPs [both ISA101 and 101b have nine E6 SLPs; ISA101 has four E7 SLPs while ISA101b has three E7 SLPs]) | ||||||
| NCT02128126 | I/II | 93 | A/R CC | ± IFNα-IIb | ISA101/101b + neoadjuvant carboplatin + paclitaxel ± bevacizumab | Aug 2018 |
| NCT04646005 | II | 105 | R/M HPV16 + CC | - | ISA101b + concurrent cemiplimab | Oct 2024 |
| NCT03258008 | II | 27 | Incurable HPV16 + OPC | - | ISA101b + concurrent utomilumab | June 2022 |
| NCT04369937 | II | 50 | Primary iIntermediate risk HPV + OPC | - | ISA101b concurrent pembrolizumab + IMRT + cisplatin | June 2024 |
| NCT04398524 | II | 86 | R/M HPV16 + OPC w/ progression on ICIs | - | ISA101b concurrent cemiplimab | Nov 2024 |
| NCT01923116 | I/II | 40 | HIV + men with HPV16 +, grade 2–3 AIN; CD4 count > 350/ul; local treatment-resistant | ± IFN-α | - | Dec 2017 |
| PDS0101 (nanoparticle-based cationic lipid R-DOTAP encapsulates six HPV16 + E6/E7 peptides; R-DOTAP elicits a cellular immune response) | ||||||
| NCT04580771 | II | 35 | Primary, LA CC | R-DOTAP# | CRT + concurrent and adjuvant PDS0101 | March 2024 |
| NCT02065973 | I | 12 | Hr-HPV + CIN 1 | R-DOTAP# | - | Dec 2015 |
| PepCan (4 peptides covering HPV16 E6) | ||||||
| NCT03821272 | I/II | 20 | HNSCC | Candida | - | December 2025 |
| NCT02481414 | II | 125 | HPV16 + cervical HSIL (CIN 2/3) | Candida | - | June 2022 |
| Autologous cell-based | ||||||
| SQZ-PBMC-HPV (peripheral blood mononuclear cells manufactured with immunogenic HPV16 epitopes) | ||||||
| NCT04084951 | I | 200 | HLA-A*02 + patients with LA/R/M HPV16 + cancers | Concurrent atezolizumab OR ipilimumab OR nivolumab OR nivolumab + ipilimumab | November 2022 | |
| NCT04892043 | I | 72 | HLA-A*02 + patients with LA/R/M HPV16 + cancers | - | Alone OR with concurrent: nivolumab OR ipilimumab OR nivolumab + ipilimumab | April 2024 |
| BVAC-C (B cells and monocytes transfected with E6/E7 gene of HPV) | ||||||
| NCT02866006 | I/II | 32 | Multiple metastatic progressive or recurrent HPV16/18 + CC | - | ± Concurrent topotecan | December 2022 |
| NCT04800978 | II | 37 | HPV16/18 + CC failure after first-line platinum-based chemotherapy | Concurrent durvalumab | August 2024 | |
| Heterologous prime-boost | ||||||
|
PVX-2 pBI-1 (small nucleic acid, prime vaccine: DNA plasmid encoding both signal peptide pNGVL4a-Sig [a detox form of HPV16 E7] AND HSP70) + TA-CIN (boost, protein vaccine) | ||||||
| NCT03911076 | II RCT | 122 | HPV16 + ASC-US, ASC-H, LSIL of cervix | - | Randomized to PVX-2 versus placebo | Jan 2024 |
|
pBI-1 (prime vaccine) + TA-HPV (tissue-antigen-HPV, boost, viral vector vaccine: recombinant vaccinia virus expressing HPV16/18 + E6/7 proteins) | ||||||
| NCT00788164 | I | 75 | HPV16 + CIN3 | ± imiquimod | pBI-1 + TA HPV OR imiquimod OR pBI-1 + TA HPV + imiquimod | Dec 2022 |
|
TheraT® vectors HB-201 attenuated arenavirus LCMV encoding inactivated HPV16 E6/E7 fusion protein + HB-202 attenuated arenavirus encoding inactivated HPV16 E6/E7 fusion protein (administered with neoadjuvant chemotherapy prior to surgery) | ||||||
| NCT05108870 | I/II | 98 | HPV + OPSCC | - | HB-201/HB-202 and carboplatin and paclitaxel ± surgery vs RT vs CRT | January 2026 |
| NCT04180215 | I/II | 100 | R/M HPV + cancers | - | - | June 2022 |
Trials in patients with HPV-mediated premalignancies part of, or encoded for, in the vaccine. ASC-US atypical squamous cells of undetermined significance, ASC-H atypical squamous cells – cannot exclude high-grade squamous intraepithelial lesion, CC cervical cancer, CIN cervical intraepithelial neoplasia, CRT chemoradiation therapy, HLA human leukocyte antigens, HPV human papillomavirus, Hr high risk, HSP heat shock protein, ICI immune checkpoint inhibitor, LA locally advanced, LSIL low-grade squamous intraepithelial lesion, OPC oropharyngeal cancer, R-DOTAP R-enantiomer of 1,2-dioleoyl-3-trimethylammonium-propane chloride, R/M recurrent/metastatic, SLPs synthetic long peptides, tLLO truncated Listeriolysin O