Trial Summary
What is the purpose of this trial?The researchers are doing this study to find out if HB-202/HB-201 is an effective treatment for people with HPV 16-positive head and neck squamous cell cancer (HPV 16+ HNSCC) who have received standard treatment for their disease but then tested positive for HPV 16-related tumor DNA in the blood through a test called NavDx. Participants will have no evidence of cancer on imaging scans (radiographically) or by medical examination (clinically). Past studies have shown that a positive NavDx test strongly suggests the possible presence of microscopic cancer, though we do not know if testing positive will definitely lead to the cancer coming back (recurrence). The NavDx blood test has not been approved by the FDA and is considered investigational.
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.
What data supports the idea that HB-202/HB-201 for Head and Neck Cancer is an effective treatment?
The available research shows that HB-202/HB-201, which targets HPV-16, is promising for treating head and neck cancer. Studies indicate that HPV-16 is a major factor in these cancers, especially in the oropharynx. The treatment aims to boost the body's immune response to fight the cancer cells. While specific data on HB-202/HB-201's effectiveness isn't detailed, similar HPV vaccines have shown potential in animal and early human trials. This suggests that enhancing the immune system can help clear HPV infections, which is a hopeful sign for this treatment's success.
12345What safety data exists for the HB-202/HB-201 treatment for head and neck cancer?
The provided research does not directly address the safety data for HB-202/HB-201 or its related names. The studies focus on HPV-associated head and neck cancers, the role of HPV-16 in these cancers, and the development of vaccines targeting HPV antigens. However, they do not provide specific safety data for the HB-202/HB-201 treatment. Further investigation into clinical trial results or specific studies on HB-202/HB-201 would be necessary to obtain safety data.
13467Is the treatment HB-202/HB-201 promising for head and neck cancer?
Yes, the treatment HB-202/HB-201 is promising for head and neck cancer because it targets HPV-16, a common cause of these cancers. It uses the body's immune system to fight cancer cells by focusing on specific proteins that are important for the cancer's growth. This approach has shown potential in improving outcomes for patients with HPV-related head and neck cancers.
13489Eligibility Criteria
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
I am 18 years old or older.
+11 more
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.
+10 more
Trial Timeline
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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: HB-200 armExperimental Treatment1 Intervention
HB-202 and HB-201 will be given in an alternating fashion as per above for a full one-year duration unless there is clinical or radiographic evident and/or pathologically confirmed recurrence.
Group II: PlaceboPlacebo Group1 Intervention
Placebo will be given via IV administration on Day 1 of each cycle on the same schedule as HB-200 treatment for a full one-year duration unless there is evidence of radiographic recurrence.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Memorial Sloan Kettering Nassau (Limited Protocol Activities)Uniondale, NY
Memorial Sloan Kettering Bergen (Limited Protocol Activities)Montvale, NJ
Memorial Sloan Kettering Westchester (Limited Protocol Activities)Harrison, NY
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)Middletown, NJ
More Trial Locations
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Who Is Running the Clinical Trial?
Memorial Sloan Kettering Cancer CenterLead Sponsor
NaverisCollaborator
Hookipa Biotech GmbHIndustry Sponsor
References
Antitumor activity of human papillomavirus type 16 E7-specific T cells against virally infected squamous cell carcinoma of the head and neck. [2021]Human papillomavirus (HPV)-associated squamous cell carcinoma of the head and neck (SCCHN) seems to be a suitable target for cancer vaccination. HPV-encoded oncogenic proteins, such as E7, are promising tumor-specific antigens and are obligatory for tumor growth. Because few immunologic studies have analyzed the endogenous HPV-specific immune response in this subset of SCCHN patients, we studied T-cell frequencies against HPV-16 E7(11-20) or E7(86-93) in tumor-bearing, human leukocyte antigen (HLA)-A*0201+ SCCHN patients, whose tumors were either HPV-16+ or HPV-16-. In HPV-16+ SCCHN patients, frequencies of T cells against either peptide were significantly elevated (P
Human papillomavirus therapeutic vaccines in head and neck tumors. [2007]Head and neck cancer represents one of the most challenging diseases as the mortality remains high despite advances in early diagnosis and treatment. Human papillomavirus has been implicated in a third of head and neck squamous cell carcinomas and human papillomavirus type 16 is strongly associated with carcinomas arising from the oropharynx, the tonsil being the preferred infected site. Novel therapeutic approaches including immunotherapy are currently under investigation. Immune vaccines developed against human papillomavirus in the genital area are already available and could simultaneously protect other anatomical localizations; however, prophylactic vaccines are expected to be effective in reducing the incidence of tumors after many years and, therefore, there is an urgent need to improve therapeutic interventions, such as immunotherapy. To date, human papillomavirus therapeutic vaccines are either at the preclinical level or at early phase human trials for genital pathologies. Nevertheless, accumulating evidence from animal and clinical studies suggests that the enhancement of specific and innate immune responses is effective in clearance of the human papillomavirus infection, promoting a cautious optimism regarding the achievement of an efficacious immunotherapy. This article reviews what has been achieved and what remains to be done in the field for the development of future viral vaccines in head and neck tumors.
Control of Spontaneous HPV16 E6/E7 Expressing Oral Cancer in HLA-A2 (AAD) Transgenic Mice with Therapeutic HPV DNA Vaccine. [2022]Human Papillomavirus type 16 (HPV16) has been associated with a subset of head and neck cancers. Two HPV encoded oncogenic proteins, E6 and E7, are important for the malignant progression of HPV-associated cancers. A spontaneous HPV16 E6/E7-expressing oral tumor model in human HLA-A2 (AAD) transgenic mice will be important for the development of therapeutic HPV vaccines for the control of HPV-associated head and neck cancers.
An updated overview of HPV-associated head and neck carcinomas. [2022]Human papilloma virus (HPV)-associated head and neck carcinoma is quite heterogeneous and most of the tumors arise in the oral cavity, oropharynx, hypopharynx and larynx. HPV was just recently recognized as an emerging risk factor for oropharyngeal squamous cell carcinoma (OSCC). HPV(+) tumors represent 5-20% of all head and neck squamous-cell carcinomas (HNSCCs) and 40-90% of those arising from the oropharynx, with widely variable rates depending on the geographic area, population, relative prevalence of environment-related SCC and detection assay. Different carcinogenic mechanisms are most likely implicated in cervical and oropharyngeal carcinogenesis. The most certain carcinogenic genotype for the head and neck region and the most common high-risk HPV genotype, HPV-16, is frequently detected in OSCC. A combination of p16INK4A expression and molecular detection of HPV DNA is the gold standard for the viral identification in tissue and exfoliated cell samples. Differences in the biology of HPV(+) and HPV(-) OSCC may have implications for the management of patients. New immunotherapy drugs based on the release of the co-inhibitory receptors, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed-death 1 (PD-1) have currently emerged. The goal of therapeutic cancer vaccination is inculcation of a persistent, tumor antigen-specific T cell response which kills tumor cells. The efficacy of the current HPV vaccines, Cervarix and Gardasil, in preventing HPV-related HNSCC is at present unknown. Treatment de-escalation is recommended as the current management of HPV-induced HNSCCs.
Human papillomavirus serologic follow-up response and relationship to survival in head and neck cancer: a case-comparison study. [2021]Human papillomavirus high risk (HPV-HR) type 16 is a significant risk factor for head and neck cancers (HNC) independent of tobacco and alcohol. The purpose of this study was to determine whether antibody levels to the HPV-16 oncoproteins E6 and E7 measured in sera collected at baseline (BL) prior to treatment and at two post-treatment follow-up (FU) visits were associated with HNC risk factors or prognosis.
Design of a phase III efficacy, immunogenicity, and safety study of 9-valent human papillomavirus vaccine in prevention of oral persistent infection in men. [2022]Seven high-risk human papillomavirus (HPV) types (16/18/31/33/45/52/58) covered by the 9-valent HPV (9vHPV) vaccine cause >90% of HPV-related head and neck cancers (HNCs). An ongoing clinical trial (NCT04199689) was designed to evaluate 9vHPV vaccine efficacy against HPV oral persistent infection, a surrogate endpoint for HPV-related HNCs.
Metastatic MHC class I-negative mouse cells derived by transformation with human papillomavirus type 16. [2018]In the endeavour to develop a model for studying gene therapy of cancers associated with human papillomaviruses (HPVs), mouse cells were transformed with the HPV type 16 (HPV16) and activated H-ras oncogenes. This was done by cotransfection of plasmid p16HHMo, carrying the HPV16 E6/E7 oncogenes, and plasmid pEJ6.6, carrying the gene coding for human H-ras oncoprotein activated by the G12V mutation, into secondary C57BL/6 mouse kidney cells. An oncogenic cell line, designated MK16/1/IIIABC, was derived. The epithelial origin of the cells was confirmed by their expression of cytokeratins. No MHC class I and class II molecules were detected on the surface of MK16/1/IIIABC cells. Spontaneous metastases were observed in lymphatic nodes and lungs after prolonged growth of MK16/1/IIIABC-induced subcutaneous tumours. Lethally irradiated MK16/1/IIIABC cells induced protection against challenge with 10(5) homologous cells, but not against a higher cell dose (5 x 10(5)). Plasmids p16HHMo and pEJ6.6 were also used for preventive immunization of mice. In comparison with a control group injected with pBR322, they exhibited moderate protection, in terms of prolonged survival, against MK16/1/IIIABC challenge (P
P16INK4a expression, human papillomavirus, and survival in head and neck cancer. [2015]Development of head and neck cancer (HNC) is associated with human papillomavirus high-risk (HPV-HR) types. The HPV E7 oncoprotein inactivates the pRB protein increasing expression of p16(INK4a). P16 expression and HPV status have been associated with differences in clinical outcomes for HNC. This study examined whether HNC prognosis was different when these biomarkers were examined as individual or joint molecular effects. Tumor tissue from 301 HNC patients were analyzed and sequenced for HPV types. P16 was evaluated by immunohistochemical staining. p16 was expressed in 35% and HPV-HR was detected in 27% of HNC patients. After adjustment for age, tobacco, and alcohol, p16+ tumors were statistically significantly associated with HPV-HR (OR=13.3, 7.1-24.9), histology, stage, grade, tumor site, and node involvement. Compared to p16+ HNC cases, those who did not express p16 had significantly worse disease-specific (DS) survival (Hazards Ratio, adj.HR=2.0. 1.0-3.9) and recurrence (adj.HR=3.6, 1.6-8.2); and HPV- cases had worse DS survival (adj.HR=2.8, 1.1-7.1) and recurrence (adj.HR=2.0, 0.8-4.8) compared to HPV-HR patients. Each of the p16/HPV groups had different survival outcomes: p16+/HPV-HR cases (referent) had the best and p16-/HPV- cases had the worst DS survival (adj.HR=3.6; 53% versus 13%, p=0.004) whereas p16+/HPV- and p16-/HPV-HR had similar DS survival (adj.HR=2.7/2.8). p16-/HPV-HR cases had a worse recurrence rate (adj.HR=7.0; 60% versus 0%, referent, p=0.08) than p16-/HPV- (adj.HR=4.5) or p16+/HPV- (adj.HR=1.8) cases. The combined p16/HPV biomarker data are associated with different survival outcomes of HNC compared to each marker evaluated separately, indicating that the two molecular mechanisms evaluated together may provide a more accurate prediction of clinical outcomes.
Patterns of antibody responses to nonviral cancer antigens in head and neck squamous cell carcinoma patients differ by human papillomavirus status. [2020]There have been hints that nonviral cancer antigens are differentially expressed in human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC). Antibody responses (AR) to cancer antigens may be used to indirectly determine cancer antigen expression in the tumor using a noninvasive and tissue-saving liquid biopsy. Here, we set out to characterize AR to a panel of nonviral cancer antigens in HPV-positive and HPV-negative HNSCC patients. A fluorescent microbead multiplex serology to 29 cancer antigens (16 cancer-testis antigens, 5 cancer-retina antigens and 8 oncogenes) and 29 HPV-antigens was performed in 382 HNSCC patients from five independent cohorts (153 HPV-positive and 209 HPV-negative). AR to any of the cancer antigens were found in 272/382 patients (72%). The ten most frequent AR were CT47, cTAGE5a, c-myc, LAGE-1, MAGE-A1, -A3, -A4, NY-ESO-1, SpanX-a1 and p53. AR to MAGE-A3, MAGE-A9 and p53 were found at significantly different prevalences by HPV status. An analysis of AR mean fluorescent intensity values uncovered remarkably different AR clusters by HPV status. To identify optimal antigen selections covering a maximum of patients with ≤10 AR, multiobjective optimization revealed distinct antigen selections by HPV status. We identified that AR to nonviral antigens differ by HPV status indicating differential antigen expression. Multiplex serology may be used to characterize antigen expression using serum or plasma as a tissue-sparing liquid biopsy. Cancer antigen panels should address the distinct antigen repertoire of HPV-positive and HPV-negative HNSCC.