Lenti-HPV-07 for HPV+ Cervical or Oropharyngeal Cancer

Recruiting at 2 trial locations

Overseen By Daniel Loera

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Theravectys S.A.

Disqualifiers: HIV, Hepatitis C, Hepatitis B

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 28 days

72 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Lenti-HPV-07 for HPV+ cervical or oropharyngeal cancer?

Research shows that HPV-positive oropharyngeal cancers generally have a better prognosis compared to HPV-negative ones, suggesting that treatments targeting HPV-related pathways, like Lenti-HPV-07, could be effective. Additionally, HPV-positive patients often have improved survival rates, indicating potential benefits of treatments focused on HPV-driven cancers. ^{1 2 3 4 5}

What makes the treatment Lenti-HPV-07 unique for HPV+ cervical or oropharyngeal cancer?

Lenti-HPV-07 is unique because it likely targets the HPV virus directly, which is a known cause of these cancers, potentially offering a more specific approach compared to traditional treatments like surgery or radiation that do not specifically target the virus. This treatment may involve a novel mechanism of action or administration route that distinguishes it from existing therapies. ^{3 6 7 8 9}

What is the purpose of this trial?

The goal of this clinical trial is to learn about the safety and efficacy of a potential new treatment called Lenti-HPV-07 in patients with a cancer induced by Human Papilloma Virus (HPV). The main questions aim to answer are: * Is Lenti-HPV-07 safe? * Does Lenti-HPV-07 induce an immune response? Participants will be assigned to a group based on their cancer type * either study drug group A: recurrent and/or metastatic cancer * or study drug group B: newly diagnosed with locally advanced cancer After they finish the study treatment, they will be followed for up to 1 year. Follow-up visits will occur via clinic visits or phone calls 4 weeks after the last study treatment and then quarterly for up to 1 year.

Eligibility Criteria

This trial is for people with HPV-related cancers of the throat or cervix. They must be in good enough health to perform daily activities (ECOG status 0 or 1) and have proper liver, kidney, lung, and blood function. It's not open to those with HIV, active hepatitis C, or any hepatitis B infection.

Inclusion Criteria

I am fully active or can carry out light work.

My liver, kidneys, lungs, and blood cells are working well.

My cancer in the throat or cervix is confirmed to be caused by HPV.

Exclusion Criteria

Seropositivity for HIV

I have Hepatitis B.

I have an active hepatitis C infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Lenti-HPV-07 based on their cancer type, either in group A for recurrent/metastatic cancer or group B for newly diagnosed locally advanced cancer

28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits occurring 4 weeks after the last study treatment and then quarterly for up to 1 year

12 months

1 visit (in-person or phone) 4 weeks post-treatment, then quarterly

Treatment Details

Interventions

• Lenti-HPV-07

Trial Overview The study tests Lenti-HPV-07 immunotherapy's safety and ability to trigger an immune response against HPV-induced cancer. Participants are grouped based on their cancer stage: recurrent/metastatic (Group A) or newly diagnosed/locally advanced (Group B), receiving up to two injections.

Participant Groups

Group I: Arm B : newly diagnosed locally advanced Experimental Treatment 1 Intervention

Participants who have newly diagnosed locally advanced HPV-related oropharyngeal cancer (defined by AJCC 8th edition \[ie, T1-2N2-N3, T3-T4N0-N3\]) or cervical cancer (stages IB to IVA) that has never been treated with curative intent, and who are candidates to begin an SoC treatment (surgery, radiation therapy with or without chemotherapy).

Group II: Arm A : Refractory newly diagnosed Experimental Treatment 1 Intervention

Refractory recurrent and/or metastatic cervical or oropharyngeal cancer that is not amenable to local therapy with curative intent (ie, surgery or radiation therapy with or without chemotherapy).

Who Is Running the Clinical Trial?

Theravectys S.A.

Lead Sponsor

Trials

2

Recruited

110+

Findings from Research

In a study of oropharyngeal squamous cell carcinomas (OPSCC) diagnosed from 2000 to 2017, only 27.1% of cases were confirmed as HPV-driven, highlighting the need for accurate identification of HPV status to avoid undertreatment.

The research found that 60.6% of OPSCC patients with p16INK4a overexpression but no HPV-DNA did not have the same risk profile or survival outcomes as HPV-positive patients, suggesting that using p16INK4a alone for treatment decisions could lead to inappropriate de-escalation of therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of p16INK4a expression as a single marker to select patients with HPV-driven oropharyngeal cancers for treatment de-escalation. Wagner, S., Prigge, ES., Wuerdemann, N., et al.[2021]

The incidence of HPV-positive oropharyngeal cancer is rapidly increasing, posing a significant public health challenge, despite having a generally better prognosis than HPV-negative cases.

Current treatment strategies for HPV-positive oropharyngeal cancer may need to be tailored based on its distinct pathological and molecular characteristics, with ongoing research into targeted therapies informed by recent genomic findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary chemotherapy and radiation as a treatment strategy for HPV-positive oropharyngeal cancer. Lui, VW., Grandis, JR.[2021]

High-risk human papillomavirus (HR-HPV), particularly HPV 16, is a major cause of oropharyngeal squamous cell carcinoma, with HPV-positive patients showing significantly better overall and disease-specific survival rates compared to those with HPV-negative tumors.

Surgical treatment remains the primary option for head and neck squamous cell carcinoma (HNSCC), and HPV-positive tumors may respond well to reduced doses of radiation or chemotherapy, indicating a potential for less aggressive treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human papillomavirus associated head and neck squamous cell carcinoma: Controversies and new concepts. Husain, N., Neyaz, A.[2020]

HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) is linked to significantly improved overall survival rates compared to HPV-negative OPSCC, with a 2-year survival rate of 92% for HPV-positive patients versus 45.8% for HPV-negative patients.

In contrast, HPV positivity does not show a significant survival advantage in nonoropharyngeal head and neck squamous cell carcinoma (non-OP HNSCC) or cervical squamous cell carcinoma (CESC), indicating that the benefits of HPV status may vary by tumor location.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Tumor Site With the Prognosis and Immunogenomic Landscape of Human Papillomavirus-Related Head and Neck and Cervical Cancers. Zhu, G., Amin, N., Herberg, ME., et al.[2022]

The UWO3 immune score, developed from a three-gene test, effectively classifies HPV+ oropharyngeal squamous cell carcinoma patients into three immune classes and is strongly associated with disease-free survival across six independent cohorts of 906 patients.

Patients classified as 'immune rich' had significantly better disease-free survival compared to those in 'immune desert' and 'mixed' classes, indicating that the UWO3 score could be a valuable tool for risk stratification and guiding treatment decisions in HPV+ OPSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-based classification of HPV-associated oropharyngeal cancer with implications for biomarker-driven treatment de-intensification. Zeng, PYF., Cecchini, MJ., Barrett, JW., et al.[2023]

High-risk HPV types 16 and 18 are linked to the development of oropharyngeal cancers, particularly in younger males who do not smoke or drink, and these cancers generally have a favorable prognosis when treated with radiotherapy.

HPV-positive patients with oropharyngeal squamous cell carcinoma have high survival rates (95% overall survival and 88% progression-free survival at two years), raising questions about the necessity of routine HPV vaccination given the positive outcomes associated with HPV status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent data about the role of human papillomavirus (HPV) in oncogenesis of head and neck cancer. Bădulescu, F., Crişan, A., Bădulescu, A., et al.[2010]

HPV-positive tumors account for a significant portion of oropharyngeal squamous cell carcinomas (OSCC), with HPV-16 being the most common high-risk genotype, highlighting the importance of HPV in the development of these cancers.

Current treatment strategies for HPV-induced head and neck squamous cell carcinomas are shifting towards de-escalation, and new immunotherapy approaches are being explored to enhance the immune response against these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An updated overview of HPV-associated head and neck carcinomas. Zaravinos, A.[2022]

In a study of 160 patients with oral potentially malignant disorders (OPMDs), approximately 19% tested positive for high-risk HPV types 16 and 18, with HPV18 being the most common subtype found in 90% of cases.

The presence of high-risk HPV was more frequently associated with moderate to severe dysplasia in oral leukoplakia (OL) and was only detected in the more severe atrophic/ulcerative forms of oral lichen planus (OLP), suggesting a potential link between HPV infection and the severity of these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High Prevalence of Human Papillomavirus Type 18 in Oral Potentially Malignant Disorders in Thailand. Kaewmaneenuan, N., Lekawanvijit, S., Pongsiriwet, S., et al.[2021]

High-risk HPV infections are primarily found in younger male nonsmokers with oropharyngeal cancers, particularly in the tonsil and base of the tongue, highlighting the importance of accurate diagnosis for better prognosis.

Among the diagnostic methods tested on 87 oral and oropharyngeal squamous cell carcinomas, Hybrid Capture 2 and Cervista showed comparable sensitivity to PCR while having fewer false positives than p16 immunostaining, suggesting they may be more reliable for detecting HPV in these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hybrid Capture 2 is as effective as PCR testing for high-risk human papillomavirus in head and neck cancers. Hooper, JE., Hebert, JF., Schilling, A., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Evaluation of p16INK4a expression as a single marker to select patients with HPV-driven oropharyngeal cancers for treatment de-escalation. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Primary chemotherapy and radiation as a treatment strategy for HPV-positive oropharyngeal cancer. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Human papillomavirus associated head and neck squamous cell carcinoma: Controversies and new concepts. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Association of Tumor Site With the Prognosis and Immunogenomic Landscape of Human Papillomavirus-Related Head and Neck and Cervical Cancers. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Immune-based classification of HPV-associated oropharyngeal cancer with implications for biomarker-driven treatment de-intensification. [2023]

6. Romania pubmed.ncbi.nlm.nih.gov

Recent data about the role of human papillomavirus (HPV) in oncogenesis of head and neck cancer. [2010]

7. United States pubmed.ncbi.nlm.nih.gov

An updated overview of HPV-associated head and neck carcinomas. [2022]

8. Thailand pubmed.ncbi.nlm.nih.gov

High Prevalence of Human Papillomavirus Type 18 in Oral Potentially Malignant Disorders in Thailand. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Hybrid Capture 2 is as effective as PCR testing for high-risk human papillomavirus in head and neck cancers. [2022]