P2/3, N=0, Withdrawn, Hookipa Biotech GmbH | N=450 --> 0 | Not yet recruiting --> Withdrawn

P1/2, N=200, Active, not recruiting, Hookipa Biotech GmbH | Recruiting --> Active, not recruiting

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

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

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

P2/3, N=450, Not yet recruiting, Hookipa Biotech GmbH

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.

P1, N=12, Recruiting, ImmunityBio, Inc. | Not yet recruiting --> Recruiting | N=18 --> 12 | Trial primary completion date: Dec 2024 --> Sep 2025

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.

The angiogenesis induced by HPV-16 E7 in NSCLC is mediated through exosomal EGFR and miR-381-3p.

P1/2, N=24, Recruiting, Mayo Clinic | Trial completion date: Jul 2024 --> Jul 2025 | Trial primary completion date: Jul 2024 --> Jul 2025

P2; Trial completion date: Jul 2024 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

P1, N=12, Completed, Advaxis, Inc. | Phase classification: P1/2 --> P1 | N=25 --> 12

P1/2, N=200, Recruiting, Hookipa Biotech GmbH | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Mar 2024 --> Jun 2025

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.

"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."

P2, N=51, Recruiting, Memorial Sloan Kettering Cancer Center

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

P1, N=18, Not yet recruiting, ImmunityBio, Inc. | Initiation date: Mar 2024 --> Jun 2024

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

P1/2, N=32, Completed, University of Southampton | Active, not recruiting --> Completed

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

P2, N=65, Active, not recruiting, ISA Pharmaceuticals | Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2023 --> Jun 2024

P1, N=36, Not yet recruiting, NexImmune Inc. | Trial completion date: Aug 2025 --> Aug 2027 | Trial primary completion date: Jul 2024 --> Jul 2026

P1/2, N=11, Completed, Dana-Farber Cancer Institute | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Feb 2023

P2, N=194, Active, not recruiting, ISA Pharmaceuticals | Trial completion date: Dec 2024 --> Jun 2025 | Trial primary completion date: Sep 2023 --> Sep 2024

P1, N=10, Terminated, Hookipa Biotech GmbH | N=27 --> 10 | Recruiting --> Terminated; Sponsor decision.

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.

P2, N=0, Withdrawn, Advaxis, Inc. | N=124 --> 0 | Unknown status --> Withdrawn

P2, N=285, Recruiting, BioNTech SE

P1/2, N=200, Recruiting, Hookipa Biotech GmbH

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.

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.

P1/2, N=60, Active, not recruiting, SQZ Biotechnologies | Recruiting --> Active, not recruiting

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.

"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."

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.

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.

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.

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

P1, N=27, Recruiting, Hookipa Biotech GmbH | Trial completion date: Aug 2023 --> Jun 2025 | Trial primary completion date: Aug 2023 --> Jun 2025

P1/2, N=200, Recruiting, Hookipa Biotech GmbH | Trial primary completion date: Jun 2023 --> Mar 2024