Combining a DNA vaccine with pembrolizumab for HPV-positive head and neck cancer

A Phase 1/2a, Open-label, Dose-finding Trial to Evaluate Safety, Immunogenicity, and Anti-tumor Activity of VB10.16 and Pembrolizumab in Patients with Unresectable Recurrent or Metastatic HPV16-positive Head-Neck Squamous Cell Carcinoma

This study is testing a new DNA vaccine combined with pembrolizumab to see if it helps people with advanced HPV-positive head and neck cancer.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 51 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Nykode Therapeutics ASA (Industry-sponsored)
• Drugs / interventions: pembrolizumab, CAR-T, chimeric antigen receptor, chemotherapy, radiation, methotrexate, prednisone, immunotherapy
• Locations: 17 sites (Olomouc and 16 other locations)
• Trial ID: NCT06016920 on ClinicalTrials.gov

What this trial studies

This multi-center clinical trial investigates the safety and efficacy of VB10.16, an investigational DNA vaccine, in combination with pembrolizumab for patients with unresectable recurrent or metastatic HPV16-positive oropharyngeal head and neck squamous cell carcinoma (HNSCC). The study is divided into two phases: a phase 1 dose escalation to determine the optimal dose of VB10.16 and a phase 2a dose expansion to evaluate the treatment's effectiveness at the selected dose. Participants will receive treatment for 48 weeks, after which they may continue with pembrolizumab based on the investigator's discretion. The trial aims to assess the immunogenicity and anti-tumor activity of the combination therapy.

Who should consider this trial

Good fit: Ideal candidates include adults with unresectable recurrent or metastatic HPV16-positive oropharyngeal HNSCC who are eligible for pembrolizumab monotherapy.

Not a fit: Patients with HPV-negative tumors or those who do not meet the specific eligibility criteria for this trial may not benefit.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat HPV-positive head and neck cancers.

How similar studies have performed: Other studies have shown promising results with similar immunotherapy approaches, indicating potential for success in this trial.

Eligibility criteria

Inclusion Criteria:

GENERAL REQUIREMENTS

1. ≥18 years of age (or as per national legal age of trial consent, whichever is higher) at date of signing the informed consent form (ICF)
2. Histologically or cytologically confirmed R/M HNSCC, located in the oropharynx, considered incurable by local therapy and eligible for monotherapy with pembrolizumab
3. HPV16 positivity of R/M oropharyngeal HNSCC confirmed by designated central laboratory
4. PD-L1 positivity (CPS ≥1) using the validated PD-L1 IHC 22C3 pharmDx (DAKO) assay.
5. Primary tumor location in the oropharynx.
6. At least 1 measurable lesion per RECIST 1.1

   ORGAN FUNCTION

   Overall function:
7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1

   Hematological function:
8. Platelets ≥100 × 10\^9/L (100,000/µL)
9. Neutrophils (absolute neutrophil count \[ANC\]) ≥1.5 × 10\^9/L (1,500/µL)
10. Hemoglobin ≥5.6 mmol/L (9.0 g/dL)

    Hepatic and hemostatic function:
11. Bilirubin (BILI), total ≤1.5 × upper limit of normal (ULN) (except Gilbert syndrome, then direct BILI ≤2 × ULN) or direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN.
12. Aspartate transaminase (AST) ≤ 2.5 × ULN or ≤5 × ULN for a patient with liver metastases.
13. Alanine transaminase (ALT) ≤ 2.5 × ULN or ≤5 × ULN for a patient with liver metastases.
14. Alkaline phosphatase ≤ 2.5 × ULN or ≤5 × ULN for a patient with liver metastases.
15. International normalized ratio (INR) or prothrombin time (PT) ≤1.5 × ULN unless the patient is receiving anticoagulant therapy, in which case PT and partial thromboplastin time (PTT)/activated PTT (aPTT) must be within therapeutic range of intended use of anticoagulants.

    Renal function:
16. Estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m\^2 using the Cockroft-Gault formula

    OTHER TRIAL REQUIREMENTS
17. Female patients of childbearing potential: negative serum pregnancy test (≤72 hours)
18. Female patients of childbearing potential must agree to use highly effective contraception throughout the trial (14 days prior to initiation of treatment for oral contraception), and for at least 120 days (according to the current version of the IB for pembrolizumab) after the last dose of pembrolizumab and up to 6 months after the last dose of VB10.16, whichever comes last.

    Male patients must agree to use male condoms during intercourse throughout the trial, and up to 3 months after the last dose of VB10.16, and must refrain from sperm donation in the same period.
19. Patients capable of giving informed consent must provide signed and dated written informed consent prior to initiation of any study-related procedures.

Exclusion Criteria:

HNSCC DISEASE

1. Has disease that is suitable for local therapy with curative intent
2. Has progressive disease ≤6 months after completion of curatively intended concurrent chemoradiotherapy for locoregionally advanced R/M oropharyngeal HNSCC
3. Primary tumor site of the oral cavity, hypopharynx, larynx or nasopharynx (any histology)
4. Rapidly progressing disease (e.g., tumor bleeding, uncontrolled tumor pain) in the opinion of the investigator

   PRIOR, CONCURRENT, OR FUTURE INTERVENTIONS
5. Has received prior palliative radiotherapy within 2 weeks of start of trial treatment or has a prior history of radiation pneumonitis
6. Any prior investigational or approved systemic antineoplastic drug or invasive medical device (including ICIs), either as monotherapy or as part of a combination regimen administered in the R/M HNSCC setting
7. Prior solid organ or tissue transplantation (except corneal transplant)
8. Prior autologous or allogeneic hematopoietic stem cell transplantation (HSCT)
9. Prior chimeric antigen receptor T (CAR-T) cell therapy
10. Prior therapy with a monoclonal or bispecific antibody or antibody fragment (or other molecule with similar mechanism of action) that engages T-cells
11. Has received a live or live-attenuated vaccine within 30 days prior to the first dose of trial intervention
12. Administration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine within 30 days prior to VB10.16 treatment start
13. Prior administration with a therapeutic HPV16 vaccine
14. Patients receiving systemic immunosuppression with immunosuppressive agents such as cyclosporine, azathioprine, methotrexate, or tumor necrosis factor alpha (TNF α) blockers for any concurrent condition
15. Chronic administration of systemic corticosteroids: prednisone \>10 mg daily (or dose equivalent)
16. Administration of G-CSF/GM-CSF or transfusions with red blood cells, platelets, or plasma components ≤2 weeks prior to VB10.16 treatment start
17. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137)
18. Has received prior surgery within 4 weeks prior to treatment
19. Any planned major surgery

    PRIOR OR CONCURRENT MORBIDITY

    Malignancy:
20. Past or current malignancy other than inclusion diagnosis, except for:

    * Malignancy treated with curative intent and with no known active disease present and has not received chemotherapy for at least 3 years before screening and felt to be at low risk for recurrence by the treating physician
    * Adequately treated breast ductal carcinoma in situ without evidence of disease
    * Adequately treated cervical carcinoma in situ, without evidence of disease
    * Adequately treated non-melanoma skin cancer without evidence of disease
    * Adequately treated superficial or in situ carcinoma of the bladder without evidence of disease
    * Prostatic intraepithelial neoplasia without evidence of prostate cancer

    Hepatic and hemostatic function:
21. Any current bleeding disorder, active bleeding, or bleeding diathesis

    Cardiovascular function:
22. Symptomatic congestive heart failure (Grade III or IV as classified by the New York Heart Association), unstable angina pectoris, or cardiac arrhythmia
23. History of myocardial infarction ≤ 6 months prior to planned VB10.16 treatment start
24. Uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg), despite optimal medical management
25. Any other significant cardiac disease(s) that, in the opinion of the investigator, is/are clinically significant and/or unacceptable

    Pulmonary function:
26. Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease

    Immune system and infectious diseases:
27. Primary immunodeficiency, other immunosuppressive disorder, and/or other causes of immunosuppression
28. Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
29. Has a known history of human immunodeficiency virus (HIV) infection.
30. Has a known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection
31. Any active, acute, or chronic infection that is uncontrolled and/or requires systemic treatment
32. Known allergies, sensitivity, or intolerance to VB10.16 (active substance or to any of the excipients), pembrolizumab (active substance or to any of the excipients), or aminoglycosides (especially kanamycin).

    Central nervous system (CNS) function:
33. Any history of intracerebral arteriovenous malformations, cerebral aneurysm, or stroke
34. Has known active CNS metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during trial screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of trial treatment
35. New (≤6 months), progressive and/or symptomatic brain metastases

    OTHER
36. Is currently participating in or has participated in a trial of an investigational agent or device in the R/M setting.
37. Has a history or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the trial or interfere with the patient's participation for the full duration of the trial, such that it is not in the best interest of the patient to participate, in the opinion of the treating investigator
38. Has a known psychiatric or substance abuse disorder that would interfere with the patient's ability to cooperate with the requirements of the trial
39. Has a concomitant medical condition requiring receipt of a therapeutic anticoagulant that, in the opinion of the treating physician, would contraindicate administration of VB10.16 and tumor biopsies
40. Female patients who are pregnant or breastfeeding

Where this trial is running

Olomouc and 16 other locations

• Fakultni nemocnice Olomouc, Olomuoc — Olomouc, Czechia (Recruiting)
• Hôpital de la Pitié - Salpétrière in Paris — Paris, Paris, France (Recruiting)
• Hospices Civils De Lyon — Lyon, France (Recruiting)
• CRLC Val d'Aurelle - Institut de Recherche en Cancerologie de Montpellier (IRCM) — Montpellier, France (Recruiting)
• Institut Gustave Roussy, Paris — Paris, France (Recruiting)
• Universität Leipzig Klinik und Poliklinik für Hals-, Nasen-, Ohrenheilkunde — Leipzig, Germany (Recruiting)
• Orszagos Onkologiai Intezet, Budapest — Budapest, Hungary (Recruiting)
• University of Bergen, Haukeland University Hospital — Bergen, Norway (Recruiting)
• Oslo Universitetssykehus — Oslo, Norway (Recruiting)
• Uniwersyteckie Cetrum Kliniczne — Gdansk, Poland (Recruiting)
• Narodowy Instytut Onkologii-im Marii Sklodowskiej-Curie Panstwowy Instytut — Gliwice, Poland (Recruiting)
• KO-MED Centra Kliniczne Lublin II, Lublin — Lublin, Poland (Recruiting)
• Hospital del Mar, Barcelona — Barcelona, Spain (Recruiting)
• Institut Catala d'Oncologia, Barcelona — Barcelona, Spain (Recruiting)
• Hospital Universitario Virgen de las Nieves, Granada — Granada, Spain (Recruiting)
• MD Anderson Cancer Center, Madrid — Madrid, Spain (Recruiting)
• East and North Hertfordshire NHS Trust Mount Vernon Hospital — London, United Kingdom (Recruiting)

Study contacts

• Principal investigator: Åse Bratland, MD, PhD — Oslo University Hospital
• Study coordinator: Chief Medical Officer

Conditions HPV Positive Oropharyngeal Squamous Cell Carcinoma; HNSCC; Unresectable; recurrent; metastatic; HPV16 positive; PD-L1