HB-202/HB-201 for Head and Neck Cancer

Recruiting at 6 trial locations

Overseen By Alan Ho, MD,PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Systemic corticosteroids, Antivirals, Immunosuppressants, others

Disqualifiers: Recurrent cancer, Autoimmune disorders, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 year

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment, HB-202/HB-201 (TheraT Vectors Expressing Human Papillomavirus 16 Positive (HPV 16+) Antigens), for individuals with head and neck cancer linked to HPV 16. The goal is to determine if this treatment is effective for those who have completed standard care but still test positive for HPV 16-related tumor DNA in their blood, which might indicate hidden cancer not visible on scans. It targets individuals who have had HPV 16-positive head and neck cancer, completed their usual treatment, and show no signs of cancer on scans but test positive for the virus in their blood. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I need to stop taking my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use systemic corticosteroids within 4 weeks of registration, and herbal remedies with immune-stimulating properties are not allowed within 28 days before the first dose. If you're on chronic antiviral medication, you cannot participate. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that HB-202/HB-201 is likely to be safe for humans?

Research shows that the HB-202 and HB-201 treatments are generally well-tolerated. In earlier studies, patients with advanced head and neck cancers received these treatments after trying several other therapies. The results indicated that most did not experience severe reactions.

While some side effects occurred, they were usually not serious, suggesting that HB-202 and HB-201 are relatively safe. These treatments aim to help the body's immune system recognize and fight cancer cells linked to HPV 16, a common virus associated with certain cancers.

For those considering joining a clinical trial, these findings suggest that the treatments are likely manageable, though individual experiences can vary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for head and neck cancer?

Researchers are excited about HB-202/HB-201 because these treatments approach head and neck cancer differently than current options like surgery, radiation, and chemotherapy. Unlike traditional treatments that often target cancer cells indiscriminately, HB-202 and HB-201 are designed to work by harnessing the body's immune system to specifically target and attack cancer cells. This innovative mechanism, called immunotherapy, aims to provide a more precise and potentially less toxic treatment option. Additionally, the alternating administration of HB-202 and HB-201 is intended to enhance the immune response, providing a novel strategy that could improve outcomes for patients with head and neck cancer.

What evidence suggests that HB-202/HB-201 might be an effective treatment for HPV 16+ head and neck cancer?

Research shows that HB-202 and HB-201, administered alternately in this trial, may help treat head and neck cancers linked to HPV 16. Earlier studies found that these treatments can quickly activate the body's immune system to find and attack cancer cells. Most patients tolerated the treatments well, experiencing no severe side effects. Evidence also suggests that combining these treatments with other drugs, such as pembrolizumab, might enhance their effectiveness. These findings indicate that HB-202 and HB-201 could help manage cancers related to HPV 16. ^{1 2 6 7 8}

Who Is on the Research Team?

Winston Wong, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with HPV 16-positive head and neck cancer who've completed standard treatment but have signs of potential microscopic cancer as indicated by a positive NavDx blood test. They should show no visible signs of cancer on scans or physical exams.

Inclusion Criteria

My kidney function is normal as of my last test.

Subject must provide voluntary study-specific informed consent prior to study entry

Adequate hematologic function within 30 days prior to registration

Exclusion Criteria

Severe, active co-morbidity

I have not received any live vaccines in the last 28 days.

I am on long-term antiviral medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive HB-202 and HB-201 in an alternating fashion or placebo for a full one-year duration

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• HB-202/HB-201

Trial Overview The study tests HB-202/HB-201 to see if it's effective in treating HPV 16+ HNSCC after standard treatments, using the investigational NavDx test to detect possible remaining cancer at the microscopic level.

How Is the Trial Designed?

Group I: HB-200 arm Experimental Treatment 1 Intervention

HB-202 and HB-201 will be given in an alternating fashion for 4 total treatments.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Naveris

Collaborator

Trials

3

Recruited

260+

Hookipa Biotech GmbH

Industry Sponsor

Trials

9

Recruited

1,100+

Published Research Related to This Trial

The MK16/1/IIIABC cell line, created by transforming mouse kidney cells with HPV16 and activated H-ras oncogenes, serves as a promising model for studying immune responses to HPV16-related cancers, as it shows spontaneous metastasis in lymph nodes and lungs.

Immunization with plasmids carrying HPV16 oncogenes provided moderate protection against tumor challenges in mice, indicating potential for developing preventive strategies against HPV-associated tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metastatic MHC class I-negative mouse cells derived by transformation with human papillomavirus type 16. Smahel, M., Sobotková, E., Bubeník, J., et al.[2018]

Human papillomavirus (HPV) is linked to a significant portion of head and neck cancers, particularly oropharyngeal carcinomas, highlighting the need for effective therapeutic strategies against HPV-related tumors.

Current research is focused on developing immunotherapy and therapeutic vaccines for HPV, with promising evidence suggesting that enhancing immune responses could effectively clear HPV infections and improve treatment outcomes for head and neck cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human papillomavirus therapeutic vaccines in head and neck tumors. Badaracco, G., Venuti, A.[2007]

In a study of 109 newly diagnosed head and neck cancer (HNC) patients, higher levels of antibodies to HPV-16 E6 and E7 were linked to increased risk factors such as younger age, more sexual partners, and worse cancer stages, indicating a potential role of these antibodies in assessing HNC risk.

Patients who were seropositive for HPV-16 E6 had significantly better overall survival rates compared to seronegative patients, suggesting that these antibodies could serve as important prognostic markers for survival in HNC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human papillomavirus serologic follow-up response and relationship to survival in head and neck cancer: a case-comparison study. Rubenstein, LM., Smith, EM., Pawlita, M., et al.[2021]

In a study of 382 head and neck squamous cell carcinoma (HNSCC) patients, antibody responses to nonviral cancer antigens were found to differ significantly between HPV-positive and HPV-negative cases, indicating distinct antigen expression patterns.

The research utilized a multiplex serology approach to analyze responses to 29 cancer antigens, revealing that 72% of patients had detectable antibody responses, which could potentially be used for noninvasive liquid biopsies to assess tumor antigen expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns of antibody responses to nonviral cancer antigens in head and neck squamous cell carcinoma patients differ by human papillomavirus status. Gangkofner, DS., Holzinger, D., Schroeder, L., et al.[2020]

In patients with HPV-16+ squamous cell carcinoma of the head and neck (SCCHN), T-cell responses against HPV-16 E7 peptides were significantly higher compared to HPV-16- patients and healthy volunteers, indicating a strong immune response linked to HPV infection.

The study suggests that HPV-16+ tumors exhibit immune escape mechanisms due to down-regulation of critical components for antigen processing, which could be targeted to enhance the effectiveness of E7-specific immunotherapy in treating HPV-associated SCCHN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of human papillomavirus type 16 E7-specific T cells against virally infected squamous cell carcinoma of the head and neck. Albers, A., Abe, K., Hunt, J., et al.[2021]

The CRT/E7(N53S) DNA vaccine effectively generated specific CD8+ T cell responses against HPV16 E7 in HLA-A2 transgenic mice, demonstrating its potential as a therapeutic option for HPV-associated head and neck cancers.

Treatment with the CRT/E7(N53S) DNA vaccine resulted in significant antitumor effects against spontaneous oral tumors induced by HPV16 E6/E7, indicating its efficacy in controlling HPV-related malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Control of Spontaneous HPV16 E6/E7 Expressing Oral Cancer in HLA-A2 (AAD) Transgenic Mice with Therapeutic HPV DNA Vaccine. Tseng, SH., Liu, L., Peng, S., et al.[2022]

In a study of 301 head and neck cancer patients, the presence of the p16 biomarker was significantly associated with high-risk HPV types, indicating that p16+ tumors have better clinical outcomes compared to p16- tumors.

When analyzing survival outcomes, patients with both p16+ and HPV-HR had the best disease-specific survival, while those with p16- and HPV- had the worst, suggesting that evaluating both biomarkers together provides a more accurate prediction of prognosis than examining them individually.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

P16INK4a expression, human papillomavirus, and survival in head and neck cancer. Smith, EM., Wang, D., Kim, Y., et al.[2015]

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]

The ongoing clinical trial (NCT04199689) is evaluating the efficacy of the 9-valent HPV vaccine in preventing oral persistent infections caused by high-risk HPV types in 6000 men aged 20-45, aiming to reduce the incidence of HPV-related head and neck cancers.

The study will assess both the primary endpoint of HPV-related oral infections and secondary endpoints related to other HPV types, while also monitoring safety through adverse event reporting for 15 days post-vaccination and serious events for 6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design of a phase III efficacy, immunogenicity, and safety study of 9-valent human papillomavirus vaccine in prevention of oral persistent infection in men. Giuliano, AR., Wilkin, T., Bautista, OM., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04180215

NCT04180215 | A Phase 1/2 Study in Patients With ... This trial studies the safety and anti-cancer effect of HB-201 and HB-202 in people. The trial is enrolling patients with metastatic/recurrent head and neck ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05108870

Study Details | NCT05108870 | TheraT® Vectors (Vaccines ... Doctors leading this study hope to learn about the safety and effectiveness of combining medications HB-201 and HB-202 (also known as TheraT® vectors) with ...

3. ir.hookipapharma.com ir.hookipapharma.com/news-releases/news-release-details/hookipa-present-complete-hb-200-phase-1-results-and-recommended

HOOKIPA to Present Complete HB-200 Phase 1 Results ... Phase 1 data show single-vector HB-201 and 2-vector HB-202/HB-201 were generally well tolerated, rapidly induced tumor-specific T cells and ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9718370/

HPV-directed Therapeutics for HPV-associated ... Lastly, preclinical studies suggest that vaccines targeting these papillomavirus proteins can generate therapeutic as well as protective effects in vivo.

5. targetedonc.com targetedonc.com/view/hb-200-vaccines-show-promised-in-hpv16-cancers

HB-200 Vaccines Show Promised in HPV16+ Cancers Adding pembrolizumab (Keytruda) to the HB-200 vaccines may help to improve efficacy in patients with human papillomavirus 16- positive (HPV16+) cancers.

6. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04180215/

Clinical Trial: NCT04180215 - HNSCC HB-201 and HB-202 are 'vectors', modified viruses intended to train the body to recognize antigens found in HPV 16+ cancer. Phase I Dose ...

7. ir.hookipapharma.com ir.hookipapharma.com/news-releases/news-release-details/hookipa-announces-positive-phase-1-data-and-phase-2-plans-hb-200

HOOKIPA announces positive Phase 1 data and Phase 2 ... Fifty-four patients had advanced HPV16+ head and neck cancers with a median of three prior therapies (range of 1-11), including a checkpoint ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.2502

First report of the safety/tolerability and preliminary ... HB-201 monotherapy and HB-201 & HB-202 2-vector alternating therapy were generally well-tolerated and showed preliminary antitumor activity as monotherapy.