Table 1.
Ongoing Therapeutic HPV vaccine clinical trials for HPV-associated diseases
| Vaccine | Antigen(s) | Construct | Study sponsor | Trial design | Estimated date of trial completion | Clinicaltrials.gov identifier |
|---|---|---|---|---|---|---|
| Persistent HPV infection and Low-grade Squamous Intraepithelial Lesion (LSIL) | ||||||
| Ad26-HPV16, Ad26-HPV18, and MVA-HPV16/18 | HPV16/18 E6/E7 | Adenovims serotype 26 (Ad26)-human papillomavirus (HPV16 or HPV18) and Modified Vaccinia Ankara (MVA)-HPV16/18 | Janssen Vaccines and prevention B.V. | Phase I/IIa in healthy female patients with persistent HPV16 or HPV18 infection of the cervix (66 estimated patients) | September 2020 | NCT03610581 |
| Atypical Squamous Cells of Undetermined Significance (ASC-US) or atypical squamous cells, cannot rule out high-grade SIL | ||||||
| pNGVL4a-Sig/E7(detox)/HSP70 + TA-CIN (PVX-2) | HPV16 E6/E7 | Plasmid encoding mutated form of HPV16-E7 linked to Sig and HSP70 and HPV16 E6, E7, and L2 fusion protein | PapiVax Biotech Inc. | Phase II in female patients with confirmation of ASC-US, HSC-H or LSIL (122 estimated patients) | December 2021 | NCT03911076 |
| pNGVL4aCRTE6E7L2 + TA-CIN (PVX-6) | HPV16 E6/E7 | Plasmid encoding Calreticulin, HPV16 E6, E7, and L2, and HPV16 E6, E7, and L2 fusion protein | PapiVax Biotech Inc. | Phase I in female patients with persistent ASC-US/LSIL (30 estimated patients) | December 2021 | NCT03913117 |
| Cervical Intraepithelial Neoplasia (CIN)/High-Grade Squamous Intraepithelial Lesion (HSIL) | ||||||
| GX-188E | HPV16/18 E6/E7 | Plasmid encoding fusion protein of HPV 16/18 E6/E7 linked to Flt3L and tpa | Genexine, Inc | Phase II in female patients with HPV16/18+ CIN2, CIN2/3, or CIN3 (134 enrolled patients) | August 2018 | NCT02596243 |
| pNGVL4a-Sig/E7(detox)/HSP70 + TA-HPV | HPV16/18 E6/E7 | Plasmid encoding mutated form of HPV16-E7 linked to Sig and HSP70 and vaccinia virus with HPV16/18 E6/E7 | Sidney Kimmel Comprehensive Cancer Center | Phase I in female patients with HPV16+ CIN3 in combination with topical imiquimod (48 estimated patients) | June 2020 | NCT00788164 |
| TVGV-1 + GPI-0100 | HPV16 E7 | Fusion protein of HPV16 E7 and ER targeting sequence | THEVAX Genetics Vaccine Co. | Phase IIa in female patients with HPV16 or HPV16/18+ cervical HSIL (10 enrolled patients) | September 2018 | NCT02576561 |
| PepCan + Candin | HPV16 E6 | HPV16 E6 peptides combined with Candida skin testing reagent candin. | University of Arkansas | Phase II in female patients with cervical HSIL (125 estimated patients) | August 2020 | NCT02481414 |
| Gardasil®9 | hrHPV16, 18, 31, 33, 45, 52 and 58 | Recombinant vaccine purified VLPs of the major capsid protein (L1) of HPV6, 11, 16, 18, 31, 33, 45, 52 and 58 | AIDS Malignancy Consortium | Phase III trial in female patients with HIV-1 infection and co-infection with hrHPV16, 18, 31, 33, 35, 45, 52 or 58 (536 estimated patients) | October 2021 | NCT03284866 |
| Gardasil®9 + imiquimod | HPV6, 11, 16, 18, 31, 33, 45, 52 and 58 | Gardasil®9: Recombinant vaccine purified VLPs of the major capsid protein (L1) of HPV6, 11, 16, 18, 31, 33, 45, 52 and 58 Imiquimod: TLR7/8 agonist | Yale University | Phase II trial in female patients with untreated HPV+ CIN2/3 (138 patients estimated) | April 2021 | NCT02864147 |
| GX-188E + GX-I7 or imiquimod | HPV16/18 E6/E7 | GX-188E: Plasmid encoding fusion protein of HPV 16/18 E6/E7 linked to Flt3L and tpa GX-17: recombinant human IL-7-hybrid Fc NT-I7 Imiquimod: TLR7/8 agonist |
Seoul St. Mary’s Hospital | Safety and efficacy trial in female patients with HPV 16/18+ CIN3 (50 patients estimated) | October 2018 | NCT03206138 |
| Anal Intraepithelial Neoplasia (AIN) | ||||||
| VGX-3100 + Electroporation | HPV16/18 E6/E7 | Mixture of three plasmids encoding optimized consensus of E6 and E7 antigen of HPV 16 and 18 | AIDS Malignancy Consortium | Phase II trial in male and female patients with HPV 16/18+ anal HSIL (80 estimated patients) | September 2021 | NCT03603808 |
| HPV-associated incurable solid tumors | ||||||
| ISA101 (SLP-HPV-01; HPV16-SLP) + nivolumab | HPV16 E6/E7 | Combination of nine HPV-16 E6 and four HPV-16 E7 synthetic peptides with incomplete Freund’s adjuvant | MD Anderson Cancer Center | Phase II trial in male and female patients with HPV16+ incurable solid tumors (OPSCC, cervical, vulvar, vaginal, anal, and penile cancer) as combination therapy with Nivolumab (34 enrolled patients) | December 2019 | NCT02426892 |
| E7 TCR T cells (T cell-based vaccine) | HPV16 E7 | Genetically engineered T cells with a T cell receptor (TCR) targeting HPV16 E7 (E7 TCR) | National Cancer Institute | Phase I/II trial in male and female patients with incurable metastatic or refractory/recurrent HPV16+ cervical, vulvar, vaginal, penile, anal, and oropharyngeal cancer) (180 estimated patients) | January 2026 | NCT02858310 |
| DPX-E7 | HPV16 E7 | Synthetic HPV16 E7 peptides packed into liposomes, freeze dried, then re-suspended in oil | Dana-Farber Cancer Institute | Phase Ib/II trial in male and female patients positive for HLA-A*02 with incurable HPV16+ head and neck, cervical or anal cancer | May 2023 | NCT02865135 |
| HARE-40 | HPV16 E6/E7 | Anti-CD40 IS-Ab ChiLob7/4 | University of Southhampton | Phase I/II trial in male and female patients with advanced HPV+ head and neck, anogenital, penile, or cervical cancer | December 2020 | NCT03418480 |
| INO-3112 + durvalumab | HPV16/18 E6/E7 | Mixture of three plasmids encoding optimized consensus of E6 and E7 antigen of HPV 16 and 18 and proprietary immune activator expressing IL-12 | MD Anderson Cancer Center | Phase II trial in male and female patients with recurrent or metastatic HPV16/18+ cancers (anal, cervical, penial, vaginal, vulval) (77 estimated patients) | January 2020 | NCT03439085 |
| Head and neck cancer | ||||||
| ADXS11-001 (ADXS-HPV) | HPV16 E7 | prfA-defective Listeria monocytogenes strain transformed with plasmid encoding HPV-16 E7 antigen fused to a fragment of nonhemolytic listeriolysin O (LLO) | Advaxis, Inc. | Phase II trial in male and female patients with HPV+ OPSCC (stage I-IV) prior to robot-assisted resection (30 estimated patients) | August 2021 | NCT02002182 |
| PepCan | HPV16 E6 | HPV16 E6 peptides | University of Arkansas | Phase I/II trial in male and female patients with head and neck cancer (20 estimated participants) | December 2021 | NCT03821272 |
| MEDI0457 + durvalumab | HPV16/18 E6/E7 | Mixture of three plasmids encoding optimized consensus of E6 and E7 antigen of HPV 16 and 18 and proprietary immune activator expressing IL-12 | MedImmune LLC | Phase Ib/IIa trial in male and female patients with HPV-associated recurrent or metastatic head and neck cancer (50 estimated patients) | August 2020 | NCT03162224 |
| TG4001 + Avelumab | HPV16 E6/E7 | Suspension of MVATG8042 vector particles, which consists of an attenuated recombinant MVA encoding modified HPV16 E6 and E7, and human interleukin-2 (IL-2) | Transgene | Phase Ib/II trial in male and female patients with HPV 16+ recurrent or metastatic OPSCC of the head and neck (52 estimated patients) | December 2021 | NCT03260023 |
| Cervical cancer | ||||||
| ADXS11-001 (Lm-LLo-E7) | HPV16 E7 | prfA-defective Listeria monocytogenes strain transformed with plasmid encoding HPV-16 E7 antigen fused to a fragment of nonhemolytic listeriolysin O (LLO) | Advaxis, Inc. | Phase II trial in female patients with persistent or recurrent squamous or non-squamous cell carcinoma of the cervix (67 estimated patients) | October 2018 | NCT01266460 |
| ISA101/ISA101b (SLP-HPV-01; HPV16-SLP) | HPV16 E6/E7 | Combination of nine HPV-16 E6 and four HPV-16 E7 synthetic peptides with incomplete Freund’s adjuvant | ISA Pharmaceuticals | Phase I/II trial in female patients with HPV-16+ advanced or recurrent cervical cancer (100 estimated patients) | April 2021 | NCT02128126 |
| TA-CIN | HPV16 E6/E7/L2 | HPV16 E6, E7, L2 fusion protein | Sidney Kimmel Comprehensive Cancer Center | Phase I trial in female patients with a history of HPV16-associated cervical cancer (stage IB1-IV) (14 patients estimated) | November 2022 | NCT02405221 |
| GX-188E + pembrolizumab | HPV16/18 E6/E7 | Plasmid encoding fusion protein of HPV 16/18 E6/E7 linked to Flt3L and tpa | Genexine, Inc | Phase Ib/II trial in female patients with advanced, non-resectable HPV+ cervical cancer (46 estimated patients) | June 2023 | NCT03444376 |
| BVAC-C | HPV16/18 E6/E7 | B cell and monocyte-based vaccine transfected with recombinant HPV E6/E7 gene and loaded with alpha-glactosyl ceramide | Celid Co., Ltd. | Phase I/II trial in females with multiple metastatic progressive or recurrent HPV 16 or 18+ cervical cancer (30 estimated patients) | August 2020 | NCT02866006 |
| INO-3112 + durvalumab | HPV16/18 E6/E7 | Mixture of three plasmids encoding optimized consensus of E6 and E7 antigen of HPV 16 and 18 and proprietary immune activator expressing IL-12 | MD Anderson Cancer Center | Phase II trial in female patients with recurrent or metastatic HPV16/18+ cancers (77 estimated patients) | January 2020 | NCT03439085 |
AIN Anal intraepithelial Neoplasia; ASC-US Atypical Squamous Cells of Undetermined Significance; ASC-H Atypical Squamous Cells, Cannot Rule out High-Grade SIL; CIN Cervical intraepithelial neoplasia; ER Endoplasmic reticulum; HIV Human immunodeficiency virus; HPV Human papillomavirus; HSIL High-grade squamous intraepithelial lesion; LSIL Low-grade squamous intraepithelial lesion; OPSCC oropharyngeal squamous cell carcinoma