^
1m
VGX-3100 and Electroporation in Treating Patients With HIV-Positive High-Grade Anal Lesions (clinicaltrials.gov)
P2, N=35, Active, not recruiting, AIDS Malignancy Consortium | Recruiting --> Active, not recruiting | N=80 --> 35 | Trial completion date: Sep 2029 --> Jan 2027 | Trial primary completion date: Sep 2029 --> Jan 2026
Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date • IO biomarker
|
PD-L1 (Programmed death ligand 1) • CD4 (CD4 Molecule)
|
PD-L1 expression
|
bizalimogene ralaplasmid (VGX-3100)
2ms
HPV-16 Vaccination and Pembrolizumab Plus Cisplatin for "Intermediate Risk" HPV-16-associated Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov)
P2, N=18, Active, not recruiting, Dan Zandberg | Recruiting --> Active, not recruiting | N=50 --> 18 | Trial completion date: Jun 2027 --> Jun 2026 | Trial primary completion date: Jun 2027 --> Jun 2025
Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date
|
Keytruda (pembrolizumab) • cisplatin • ISA101
2ms
Observational study on the correlation between the immune response of patients' peripheral blood stimulated by therapeutic HPV mRNA vaccine in vitro and the pathological results and clinical prognosis of patients (ChiCTR2400087487)
P=N/A, N=150, Not yet recruiting, Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine; Renji Hospital affiliated to Shanghai Jiaotong University School of Medi
New trial
|
BNT113
4ms
New P2/3 trial • Metastases
|
Keytruda (pembrolizumab) • eseba-vec (HB-200) • HB-201
4ms
Phase II multicenter, randomized, double-blind, placebo-controlled study evaluating the efficacy of HB-200 in patients with detectable TTMV-HPV DNA after definitive treatment for HPV16 + HNSCC (ESMO 2024)
The primary objective is to assess the disease-free survival (DFS) for pts enrolled in the study receiving either HB-200 or placebo. The secondary objectives include overall survival, and safety.
P2 data • Clinical
|
NavDx®
|
eseba-vec (HB-200)
5ms
IBRX-042 In Subjects With HPV-Associated Tumors (clinicaltrials.gov)
P1, N=12, Recruiting, ImmunityBio, Inc. | Not yet recruiting --> Recruiting | N=18 --> 12 | Trial primary completion date: Dec 2024 --> Sep 2025
Enrollment open • Enrollment change • Trial primary completion date
5ms
T-cell immunity induced and reshaped by an anti-HPV immuno-oncotherapeutic lentiviral vector. (PubMed, NPJ Vaccines)
Here, we first established that anti-vector immunity induced by Lenti-HPV-07 prime has no impact on the efficacy of a homologous boost to amplify anti-HPV T-cell immunity. We then demonstrated that the effector functions of such Lenti-HPV-07-induced T cells synergize with anti-checkpoint inhibitory treatments by systemic administration of anti-TIM3 or anti-NKG2A monoclonal antibodies. While Lenti-HPV-07 is about to enter a Phase I/IIa clinical trial, these results will help better elucidate its mode of action in immunotherapy against established HPV-mediated malignancies.
Journal • Viral vector
|
CD8 (cluster of differentiation 8) • KLRC1 (Killer Cell Lectin Like Receptor C1)
|
HPV-T
6ms
Exosomal EGFR and miR-381-3P Mediate HPV-16 E7 Oncoprotein-Induced Angiogenesis of Non-Small Cell Lung Cancer. (PubMed, Front Biosci (Landmark Ed))
The angiogenesis induced by HPV-16 E7 in NSCLC is mediated through exosomal EGFR and miR-381-3p.
Journal
|
EGFR (Epidermal growth factor receptor) • MIR381 (MicroRNA 381)
6ms
A Vaccine (PDS0101) Alone or in Combination With Pembrolizumab for the Treatment of Locally Advanced Human Papillomavirus-Associated Oropharynx Cancer (clinicaltrials.gov)
P1/2, N=24, Recruiting, Mayo Clinic | Trial completion date: Jul 2024 --> Jul 2025 | Trial primary completion date: Jul 2024 --> Jul 2025
Trial completion date • Trial primary completion date
|
Keytruda (pembrolizumab) • Versamune HPV
6ms
VERSATILE002: Study of PDS0101 and Pembrolizumab Combination I/O in Subjects With HPV16 + Recurrent and/or Metastatic HNSCC (clinicaltrials.gov)
P2; Trial completion date: Jul 2024 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Jun 2025
Trial completion date • Trial primary completion date • Metastases
|
PD-L1 (Programmed death ligand 1)
|
PD-L1 expression
|
PD-L1 IHC 22C3 pharmDx
|
Keytruda (pembrolizumab) • Versamune HPV
6ms
Axalimogene Filolisbac (ADXS11-001) High Dose in Women With Human Papillomavirus (HPV) + Cervical Cancer (clinicaltrials.gov)
P1, N=12, Completed, Advaxis, Inc. | Phase classification: P1/2 --> P1 | N=25 --> 12
Phase classification • Enrollment change
|
Lovaxin C (axalimogene filolisbac)
7ms
A Phase 1/2 Study in Patients With HPV16+ Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma and Other Cancers (clinicaltrials.gov)
P1/2, N=200, Recruiting, Hookipa Biotech GmbH | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Mar 2024 --> Jun 2025
Trial completion date • Trial primary completion date • Metastases
|
Keytruda (pembrolizumab) • eseba-vec (HB-200) • HB-201
7ms
Combination of cemiplimab and ISA101b vaccine for the treatment of recurrent/metastatic HPV16 cervical cancer. (ASCO 2024)
Results from this phase 2 study of cemiplimab + ISA101b in patients with recurrent HPV16 cervical cancer show clinical benefit, especially in patients with high PD-L1 expression, and no unexpected safety signals, supporting further research.
PD(L)-1 Biomarker • IO biomarker • Metastases
|
VENTANA PD-L1 (SP263) Assay
|
Libtayo (cemiplimab-rwlc) • ISA101
7ms
Naveris Announces Launch of Phase II Clinical Study in MRD+ Head and Neck Cancer (Businesswire)
"Naveris, Inc...announced the launch of a Phase II clinical study in minimal residual disease positive (MRD+) HPV-driven head and neck cancer. The study will be led by Memorial Sloan Kettering Cancer Center (MSKCC), a top cancer treatment and research institution. The primary objective of this multicenter randomized study is to evaluate the efficacy of HB-200, a novel intervention, for patients with HPV16+ head and neck squamous cell cancer (HNSCC) with molecular relapse, defined as the presence of circulating Tumor Tissue Modified Viral (TTMV)-HPV DNA without clinical or radiographic evidence of recurrence following definitive treatment."
Trial status
|
NavDx®
|
eseba-vec (HB-200)
7ms
New P2 trial
|
eseba-vec (HB-200) • HB-201
8ms
Phase Ib/II of TG4001 and Avelumab in HPV16 Positive R/M Cancers (clinicaltrials.gov)
P1/2, N=150, Active, not recruiting, Transgene | Recruiting --> Active, not recruiting | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2024
Enrollment closed • Trial completion date • Trial primary completion date • Metastases
|
Bavencio (avelumab) • tipapkinogene sovacivec (TG4001)
8ms
IBRX-042 In Subjects With HPV-Associated Tumors (clinicaltrials.gov)
P1, N=18, Not yet recruiting, ImmunityBio, Inc. | Initiation date: Mar 2024 --> Jun 2024
Trial initiation date
9ms
COMMANDER-001: Study of SQZ-eAPC-HPV in Patients With HPV16+ Recurrent, Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
P1/2, N=20, Terminated, SQZ Biotechnologies | N=60 --> 20 | Trial completion date: Mar 2024 --> Nov 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Mar 2024 --> Nov 2023; Corporate Decision
Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Combination therapy • Checkpoint inhibition • Metastases
|
Keytruda (pembrolizumab)
10ms
HARE-40: HPV Anti-CD40 RNA vaccinE (clinicaltrials.gov)
P1/2, N=32, Completed, University of Southampton | Active, not recruiting --> Completed
Trial completion
|
BNT113
10ms
A Vaccine (PDS0101) and Chemoradiation for the Treatment of Stage IB3-IVA Cervical Cancer, the IMMUNOCERV Trial (clinicaltrials.gov)
P2, N=22, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=35 --> 22 | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Mar 2025
Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date • Metastases
|
ALK (Anaplastic lymphoma kinase)
|
cisplatin • Versamune HPV
10ms
ProcemISA: A Phase II Study of Cemiplimab and ISA101b in Patients With Recurrent/Metastatic HPV16 Positive OPC (clinicaltrials.gov)
P2, N=65, Active, not recruiting, ISA Pharmaceuticals | Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2023 --> Jun 2024
Enrollment closed • Trial primary completion date • Metastases
|
Libtayo (cemiplimab-rwlc) • ISA101
10ms
Autologous T Cells Targeting HPV16 HPV18 & Survivin in Patients With R/R HPV-related Oropharyngeal Cancers (clinicaltrials.gov)
P1, N=36, Not yet recruiting, NexImmune Inc. | Trial completion date: Aug 2025 --> Aug 2027 | Trial primary completion date: Jul 2024 --> Jul 2026
Trial completion date • Trial primary completion date
|
HLA-A (Major Histocompatibility Complex, Class I, A)
|
cyclophosphamide • fludarabine IV • NEXI-003
11ms
Trial To Test Safety And Efficacy Of Vaccination For Incurable HPV 16-Related Oropharyngeal, Cervical And Anal Cancer (clinicaltrials.gov)
P1/2, N=11, Completed, Dana-Farber Cancer Institute | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Feb 2023
Trial completion • Trial completion date
|
HLA-A (Major Histocompatibility Complex, Class I, A)
|
HLA-A*02 • HLA-A2 positive
|
cyclophosphamide • DPX-E7
11ms
OpcemISA: A Randomized Phase 2 Study of Cemiplimab ± ISA101b in HPV16-Positive OPC (clinicaltrials.gov)
P2, N=194, Active, not recruiting, ISA Pharmaceuticals | Trial completion date: Dec 2024 --> Jun 2025 | Trial primary completion date: Sep 2023 --> Sep 2024
Trial completion date • Trial primary completion date
|
PD-L1 (Programmed death ligand 1)
|
PD-L1 expression
|
Libtayo (cemiplimab-rwlc) • ISA101
11ms
A Study HB-201 in Patients With Newly Diagnosed HPV16+ Oropharynx or Locally Advanced Cervical Cancer (clinicaltrials.gov)
P1, N=10, Terminated, Hookipa Biotech GmbH | N=27 --> 10 | Recruiting --> Terminated; Sponsor decision.
Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Metastases
|
HB-201
11ms
Preferential Expansion of HPV16 E1-Specific T Cells from Healthy Donors' PBMCs after Ex Vivo Immunization with an E1E2E6E7 Fusion Antigen. (PubMed, Cancers (Basel))
Therapeutic HPV vaccines in clinical development show great promise in improving outcomes for patients who mount an anti-HPV T-cell response; however, far from all patients elicit a sufficient immunological response...We suggest that this assay can be a valuable translational tool to complement the known animal models, not only for HPV therapeutic vaccines, and supports the use of E1 as an immunotherapeutic target. Nevertheless, the findings reported here need to be validated in a larger number of donors and preferably in patient samples.
Preclinical • Journal
|
TRIP13 (Thyroid Hormone Receptor Interactor 13)
|
HPV-T
11ms
Enrollment change • Trial withdrawal
|
pemetrexed • Lovaxin C (axalimogene filolisbac)
11ms
Trial completion date • Trial primary completion date • Combination therapy • Metastases
|
PD-L1 (Programmed death ligand 1)
|
Keytruda (pembrolizumab) • BNT113
11ms
Trial completion date • Trial primary completion date • Metastases
|
Keytruda (pembrolizumab) • eseba-vec (HB-200) • HB-201
12ms
HPV16 E7 protein antagonizes TNF-α-induced apoptosis of cervical cancer cells via Daxx/JNK pathway. (PubMed, Microb Pathog)
Here, it was found that HPV16 E7 can interact with Daxx in HeLa or C33A cells by co-immunoprecipitation. HPV16 E7 protein treatment can up-regulate Daxx protein expression, while the interference in Daxx expression and the agonists for JNK can both reduce the antagonistic effects of HPV16 E7 on TNF-α-induced apoptosis, suggesting that Daxx/JNK pathway may be involved in the anti-apoptotic activity of HPV16 E7.
Journal
|
TNFA (Tumor Necrosis Factor-Alpha) • DAXX (Death-domain associated protein)
1year
A Therapeutic DNA Vaccine Targeting HPV16 E7 in Combination with Anti-PD-1/PD-L1 Enhanced Tumor Regression and Cytotoxic Immune Responses. (PubMed, Int J Mol Sci)
In addition, combination therapy inhibited the number of capillaries in tumor tissues and increased the thickness of the tumor capsule. Thus, Ad-E7 vaccination, in combination with an immune checkpoint blockade, may benefit patients with HPV16-associated cervical cancer.
Journal • Combination therapy • PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha)
1year
COMMANDER-001: Study of SQZ-eAPC-HPV in Patients With HPV16+ Recurrent, Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
P1/2, N=60, Active, not recruiting, SQZ Biotechnologies | Recruiting --> Active, not recruiting
Enrollment closed • Combination therapy • Checkpoint inhibition • Metastases
|
Keytruda (pembrolizumab)
1year
A replicative recombinant HPV16 E7 expression virus upregulates CD36 in C33A cells. (PubMed, Front Microbiol)
The successful expression of HPV16 E7 in cells demonstrates that the replicated recombinant virus retains the replication and infection abilities of Ad4, while also upregulating the CD36 gene involved in the PI3K-Akt signaling and p53 pathways, thereby promoting cell proliferation. The outcome of this study provides a novel perspective and serves as a solid foundation for further exploration of HPV-related carcinogenesis and the development of replicative HPV recombinant vaccines capable of inducing protective immunity against HPV.
Journal
|
CD36 (thrombospondin receptor)
1year
HPV Circulating Cell-Free DNA Kinetics in Cervical Cancer Patients Undergoing Definitive Chemoradiation. (PubMed, Int J Radiat Oncol Biol Phys)
"Forty-seven patients with cervical cancer were enrolled on this study between 2017 and 2022, either as part of a standard-of-care (SOC) treatment banking protocol (33 patients) or as part of a clinical trial combining a therapeutic HPV vaccine (PDS0101; Immunocerv, 14 patients)...Treatment with a therapeutic HPV vaccine was associated with a more rapid decline in cfHPV DNA. Further analysis of cfDNA kinetics could provide valuable information on the relationship between cfDNA levels, treatment response, and clinical outcomes."
Journal
|
AmpFire HPV Assay
|
Versamune HPV
1year
Characterization of tumor specific CD8+ T cell responses in patients with recurrent/metastatic HPV16-positive head and neck cancer receiving HB-200 monotherapy as second or later line treatment in a phase 1 study (SITC 2023)
HB-200 is comprised of an alternating sequence of two replicating attenuated arenavirus vectors derived from LCMV (HB-201) and Pichinde virus (HB-202), respectively, expressing the same non-oncogenic HPV16 E7E6 fusion protein. Conclusions HB-200 monotherapy induces promising HPV16+ tumor-specific T cell responses and tumor infiltration in heavily pre-treated patients. This immune response coupled with clinical benefit in monotherapy suggests that HB-200 may enhance and strengthen current immunotherapy approaches by targeting specific tumor antigens.
Clinical • P1 data • Metastases
|
CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma)
|
eseba-vec (HB-200) • HB-201
1year
Skin-Grafting and Dendritic Cell "Boosted" Humanized Mouse Models Allow the Pre-Clinical Evaluation of Therapeutic Cancer Vaccines. (PubMed, Cells)
In conclusion, we successfully established two humanized mouse models that exhibited strong antigen-specific responses and demonstrated tumor regression following vaccination. These models serve as valuable platforms for assessing the efficacy of therapeutic cancer vaccines targeting HPV16-dysplastic skin and diverse tumor antigens specifically delivered to CD141 DCs.
Preclinical • Journal
|
FLT3 (Fms-related tyrosine kinase 3) • CD8 (cluster of differentiation 8) • HLA-A (Major Histocompatibility Complex, Class I, A)
|
HLA-A*02
|
HPV-T
over1year
Polyfunctional HPV16-Specific T cell responses in subjects receiving PDS0101 and pembrolizumab combination treatment for recurrent/metastatic HPV16-positive head and neck squamous cell carcinoma (HNSCC) (ESMO 2023)
Conclusions The PDS0101/pembrolizumab combination generates polyfunctional CD4 and CD8 T cells that secrete multiple cytokines and chemokines associated with a predominant effector, stimulatory functional profile. Further investigation of T cell polyfunctionality and correlation with clinical outcomes is warranted.
Clinical • PD(L)-1 Biomarker • IO biomarker • Metastases
|
CD8 (cluster of differentiation 8) • TNFA (Tumor Necrosis Factor-Alpha) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • CD4 (CD4 Molecule) • IL2 (Interleukin 2) • CCL4 (Chemokine (C-C motif) ligand 4) • GZMB (Granzyme B)
|
Keytruda (pembrolizumab) • Versamune HPV
over1year
Combination Immunotherapy in Subjects With Advanced HPV Associated Malignancies (clinicaltrials.gov)
P1/2, N=51, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2024 --> Jul 2026 | Trial primary completion date: Jun 2023 --> Jul 2022
Trial completion date • Trial primary completion date • Metastases
|
PD-L1 (Programmed death ligand 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CD4 (CD4 Molecule)
|
PD-L1 negative
|
bintrafusp alfa (M7824) • Versamune HPV • PDS01ADC
over1year
A Study HB-201 in Patients With Newly Diagnosed HPV16+ Oropharynx or Locally Advanced Cervical Cancer (clinicaltrials.gov)
P1, N=27, Recruiting, Hookipa Biotech GmbH | Trial completion date: Aug 2023 --> Jun 2025 | Trial primary completion date: Aug 2023 --> Jun 2025
Trial completion date • Trial primary completion date • Tumor mutational burden • IO biomarker • Metastases
|
TMB (Tumor Mutational Burden)
|
HB-201
over1year
A Phase 1/2 Study in Patients With HPV16+ Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma and Other Cancers (clinicaltrials.gov)
P1/2, N=200, Recruiting, Hookipa Biotech GmbH | Trial primary completion date: Jun 2023 --> Mar 2024
Trial primary completion date • Metastases
|
Keytruda (pembrolizumab) • eseba-vec (HB-200) • HB-201
over1year
VERSATILE002: Study of PDS0101 and Pembrolizumab Combination I/O in Subjects With HPV16 + Recurrent and/or Metastatic HNSCC (clinicaltrials.gov)
P2; Recruiting --> Active, not recruiting | Trial primary completion date: May 2023 --> Jun 2024
Trial primary completion date • Enrollment closed • Metastases
|
PD-L1 (Programmed death ligand 1)
|
PD-L1 expression
|
PD-L1 IHC 22C3 pharmDx
|
Keytruda (pembrolizumab) • Versamune HPV
over1year
New P1 trial • Metastases
|
HPV-T