Safety and Efficacy of VB10.16 and Pembrolizumab in Patients With Head-Neck Squamous Cell Carcinoma

August 24, 2026 updated by: Nykode Therapeutics ASA

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

This is a multi-center study in patients with un-resectable Recurrent or Metastatic HPV16-positive oropharyngeal Head and Neck Squamous Cell Carcinoma (HNSCC). The trial is designed to investigate VB10.16, an investigational therapeutic DNA vaccine in combination with another medicine, pembrolizumab, which is the standard of care for patients with previously untreated metastatic or resectable recurrent PD-L1 positive HNSCC. The study is divided in 2 parts:

  • Phase 1: Dose escalation to evaluate safety and determine the recommended phase 2 dose (RP2D) of VB10.16
  • Phase 2: Randomized comparison of VB10.16 in combination with pembrolizumab versus pembrolizumab monotherapy The goal of Phase 1 is to evaluate the safety and tolerability of the combined treatment and to decide on the dose of VB10.16 to be used in the second part of the trial. The randomized Phase 2 will consist of 2 parallel arms exploring VB10.16 at the selected RP2D from the escalation phase in combination with pembrolizumab SoC (experimental arm, Arm A), versus pembrolizumab alone (control arm, Arm B).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This Phase 1/2, open-label, dose-escalation and randomized trial is designed to evaluate the safety, tolerability, anti-tumor activity and immunogenicity of VB10.16 in combination with pembrolizumab in patients with HPV16-positive, PD-L1-positive unresectable recurrent or metastatic (r/m) oropharyngeal HNSCC, who are eligible for pembrolizumab monotherapy as standard of care (SoC) in the first-line setting. The trial consists of 2 consecutive phases with separate patient groups and is designed to determine the RP2D of VB10.16 in combination with pembrolizumab through dose-escalation of 3 mg, 6 mg, and 9 mg VB10.16, and to evaluate efficacy of the RP2D of VB10.16 when combined with pembrolizumab compared to pembrolizumab alone in Phase 2.

Phase 1: The dose escalation Phase 1 will consist of 3 dosing cohorts to evaluate VB10.16 at 3 mg (Cohort 1), 6 mg (Cohort 2), and 9 mg (Cohort 3). The 3 mg cohort will utilize a partial accelerated titration approach with a single patient41. The 6 mg cohort will follow a standard titration with 3 patients, and the 9 mg cohort will include a minimum of 6 patients to safety-clear the dose as a potential RP2D in the randomized phase.

Phase 2: The randomized Phase 2 will consist of 2 parallel arms exploring VB10.16 at the selected RP2D from the escalation phase in combination with pembrolizumab SoC (experimental arm, Arm A), versus pembrolizumab alone (control arm, Arm B). Allocation will be 1:1 by centralized block randomization, stratified by PD-L1 expression (CPS 1-19 versus ≥20) and ECOG PS (0 versus 1) Treatment duration is up to 2 years or until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Study Type

Interventional

Enrollment (Estimated)

110

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Montpellier, France, 34298
        • Recruiting
        • CRLC Val d'Aurelle - Institut de Recherche en Cancerologie de Montpellier (IRCM)
        • Contact:
        • Contact:
          • Vinches
      • Paris, France
        • Recruiting
        • Institut Gustave Roussy
  • Germany
      • Giessen, Germany
        • Recruiting
        • Universitaetsklinikum Giessen und Marburg GmbH - Klinik fuer Hals, Nasen- und Ohrenheilkunde
  • Hungary
      • Budapest, Hungary
        • Recruiting
        • National Institute of Oncology
  • Norway
      • Bergen, Norway
        • Recruiting
        • University of Bergen, Haukeland University Hospital
        • Contact:
          • Marianne Brydoy, MD
      • Oslo, Norway
        • Recruiting
        • Oslo Universitetssykehus
        • Contact:
          • Åse Bratland, MD, PhD
  • Poland
      • Gdansk, Poland
        • Recruiting
        • Uniwersyteckie Cetrum Kliniczne
      • Gliwice, Poland
        • Recruiting
        • Narodowy Instytut Onkologii-im Marii Sklodowskiej-Curie Panstwowy Instytut
        • Contact:
          • Tomasz Rutkowski, Dr
  • Spain
      • Barcelona, Spain
        • Recruiting
        • Hospital del Mar
      • Barcelona, Spain
        • Recruiting
        • ICO Hospitalet (Hospital Duran i Reynals)
      • Madrid, Spain
        • Recruiting
        • MD Anderson Cancer Center
  • United Kingdom
      • London, United Kingdom
        • Recruiting
        • East and North Hertfordshire NHS Trust Mount Vernon Hospital
        • Contact:
          • Saira Khalique, Dr

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

KEY INCLUSION CRITERIA:

  • ≥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).
  • Histologically or cytologically confirmed r/m HNSCC, located in the oropharynx, considered incurable by local therapy and eligible for monotherapy with pembrolizumab.
  • HPV16 positivity of r/m oropharyngeal HNSCC confirmed by designated central laboratory.

laboratory.

  • PD-L1 positivity (CPS ≥1) using the validated PD-L1 IHC 22C3 pharmDx (DAKO) assay.
  • Primary tumor location in the oropharynx.
  • At least 1 measurable lesion per RECIST 1.1.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1.
  • Life expectancy of ≥3 months, as determined by Gustave Roussy Immuno (GRIm) score 0-1.

KEY Exclusion criteria:

HNSCC DISEASE

  • Has disease that is suitable for local therapy with curative intent.
  • Has progressive disease ≤6 months after completion of curatively intended concurrent chemoradiotherapy for locoregionally advanced r/m oropharyngeal HNSCC.
  • Primary tumor site of the oral cavity, hypopharynx, larynx or nasopharynx (any histology).
  • Rapidly progressing disease (e.g., tumor bleeding, uncontrolled tumor pain) in the opinion of the investigator. PRIOR, CONCURRENT, OR FUTURE INTERVENTIONS
  • Has received prior palliative radiotherapy within 2 weeks of start of trial treatment or has a prior history of radiation pneumonitis.
  • 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.
  • Prior solid organ or tissue transplantation (except corneal transplant).
  • Prior autologous or allogeneic hematopoietic stem cell transplantation (HSCT).
  • Prior chimeric antigen receptor T (CAR-T) cell therapy.
  • Prior therapy with a monoclonal or bispecific antibody or antibody fragment (or other molecules with similar mechanism of action) that engages T-cells.
  • Has received a live or live-attenuated vaccine within 30 days prior to the first dose of trial intervention.
  • Administration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine within 30 days prior to trial treatment start.
  • Prior administration with a therapeutic HPV16 vaccine.
  • Patients receiving systemic immunosuppression with immunosuppressive agents such as cyclosporine, azathioprine, methotrexate, or tumor necrosis factor alpha (TNF-α) blockers for any concurrent condition.
  • Chronic administration of systemic corticosteroids: prednisone >10 mg daily (or dose equivalent).
  • 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), including pembrolizumab in the locoregional setting.
  • Primary immunodeficiency, other immunosuppressive disorder, and/or other causes of immunosuppression.
  • 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. Accordingly, routine brain MRI at screening is not mandatory for all patients, only for those with previously treated but stable brain metastases.
  • New (≤6 months), progressive and/or symptomatic brain metastases.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase1: Dose Escalation: 3 mg VB10.16 + Pembrolizumab

3 mg of VB10.16 via i.m. needle-free injections in the deltoid muscles

Pembrolizumab will be given as standard of care/ background medication via i.v. infusions
Drug: Pembrolizumab
Intravenous infusion.
Other Names:
  • KEYTRUDA®
Biological: VB10.16
Intramuscular injection using a PharmaJet needle-free injection system
Experimental: Phase 1: Dose Escalation: 6 mg VB10.16 + Pembrolizumab

6 mg of VB10.16 via i.m. needle-free injections in the deltoid muscles and quadriceps or gluteus muscles

Pembrolizumab will be given as standard of care/ background medication via i.v. infusions
Drug: Pembrolizumab
Intravenous infusion.
Other Names:
  • KEYTRUDA®
Biological: VB10.16
Intramuscular injection using a PharmaJet needle-free injection system
Experimental: Phase 1: Dose Escalation: 9 mg VB10.16 + Pembrolizumab

9 mg of VB10.16 via i.m. needle-free injections in the deltoid muscles and quadriceps and/or gluteus muscle

Pembrolizumab will be given as standard of care/ background medication via i.v. infusions
Drug: Pembrolizumab
Intravenous infusion.
Other Names:
  • KEYTRUDA®
Biological: VB10.16
Intramuscular injection using a PharmaJet needle-free injection system
Experimental: Phase 2: Arm A: VB10.16 (recommended Phase 2 Dose) + Pembrolizumab
Patients randomized to receive VB10.16 at the Recommended Phase 2 Dose (RP2D) in combination with pembrolizumab. Patients will receive pembrolizumab plus the selected RP2D of VB10.16.
Drug: Pembrolizumab
Intravenous infusion.
Other Names:
  • KEYTRUDA®
Biological: VB10.16
Intramuscular injection using a PharmaJet needle-free injection system
Experimental: Phase 2: Active comparator ph 2, Arm B: Pembrolizumab Monotherapy
Patients randomized to receive pembrolizumab monotherapy.
Drug: Pembrolizumab
Intravenous infusion.
Other Names:
  • KEYTRUDA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1: Dose Escalation: Dose Limiting Toxicities (DLT)
Time Frame: 42 days
Proportion of patient with Dose Limiting Toxicities (DLTs).
42 days
Phase 2: Dose expansion: Objective Response Rate (ORR)
Time Frame: Up to 2 years
Objective Response Rate (ORR), defined as the proportion of patients who have either confirmed CR or confirmed PR as best overall response per RECIST 1.1.
Up to 2 years
Phase 2: Dose Expansion: Progression-Free Survival (PFS)
Time Frame: Up to 2 years
PFS defined as the time from randomization to the first documented disease progression according to RECIST 1.1 or death from any cause, whichever occurs first.
Up to 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 2: Dose Expansion: Disease Control Rate (DCR)
Time Frame: Up to 2 years
Disease control rate (DCR), defined as the proportion of patients who have either confirmed CR, confirmed PR, or SD as BOR according to RECIST 1.1.
Up to 2 years
Phase 2: Dose Expansion: Duration of response (DOR)
Time Frame: Up to 2 years
Duration of response (DOR), defined as time from the date of first documented response of CR or PR to the date of the first documented progression or death due to any cause.
Up to 2 years
Phase 2: Dose Expansion: Duration of complete response (DOCR)
Time Frame: Up to 2 years
Duration of complete response (DOCR), defined as time from the date of first documented response of CR to the date of the first documented progression or death due to any cause.
Up to 2 years
Phase 2: Dose Expansion: Duration of Disease Control (DODC)
Time Frame: Up to 2 years
Duration of Disease Control (DODC), defined as time from the date of first documented response of CR, PR or SD to the date of the first documented progression or death due to any cause.
Up to 2 years
Phase 2: Dose Expansion: Time to Response (TTR)
Time Frame: Up to 2 years
Time to Response (TTR), s defined as the time from VB10.16 treatment start date to the date of first documented response of either confirmed CR or confirmed PR.
Up to 2 years
Phase 1+2: Incidence of Treatment-Emergent and Treatment-Related Adverse Events (TEAEs) and (TRAEs)
Time Frame: Up to 2 years
Number and percentage of participants experiencing treatment-emergent/Treatment related adverse events, including Grade ≥3 adverse events, serious adverse events (SAEs), adverse events leading to treatment discontinuation, and adverse events of special interest.
Up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nykode Therapeutics ASA

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Principal Investigator: Åse Bratland, MD, PhD, Oslo University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 19, 2023

Primary Completion (Estimated)

January 1, 2029

Study Completion (Estimated)

December 1, 2030

Study Registration Dates

First Submitted

August 24, 2023

First Submitted That Met QC Criteria

August 24, 2023

First Posted (Actual)

August 30, 2023

Study Record Updates

Last Update Posted (Actual)

August 26, 2026

Last Update Submitted That Met QC Criteria

August 24, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VB-C-03
  • 2022-503055-26-00 (Other Identifier: EU Trial Number)
  • KEYNOTE-E72 (Other Identifier: Merck Sharp & Dohme LLC)
  • MK-3475-E72 (Other Identifier: Merck Sharp & Dohme LLC)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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