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

NCT06016920 | Recruiting Phase 1

• 4 other identifiers: VB-C-032022-503055-26-00KEYNOTE-E72MK-3475-E72
• Study Type: interventional
• Target: 110
• Locations: 7 countries
• Sites: 12

Brief Summary

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).

Conditions

HPV Positive Oropharyngeal Squamous Cell Carcinoma; HNSCC

Keywords

Unresectable; recurrent; metastatic; HPV16 positive; PD-L1

Outcome Measures

Primary Outcomes (3)

• Phase 1: Dose Escalation: Dose Limiting Toxicities (DLT)

  Proportion of patient with Dose Limiting Toxicities (DLTs).

  42 days

• Phase 2: Dose expansion: Objective Response Rate (ORR)

  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)

  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 Outcomes (6)

• Phase 2: Dose Expansion: Disease Control Rate (DCR)

  Up to 2 years

• Phase 2: Dose Expansion: Duration of response (DOR)

  Up to 2 years

• Phase 2: Dose Expansion: Duration of complete response (DOCR)

  Up to 2 years

• Phase 2: Dose Expansion: Duration of Disease Control (DODC)

  Up to 2 years

• Phase 2: Dose Expansion: Time to Response (TTR)

  Up to 2 years

Study Arms (5)

Phase1: Dose Escalation: 3 mg VB10.16 + Pembrolizumab

EXPERIMENTAL

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

Biological: VB10.16; Drug: Pembrolizumab

Phase 1: Dose Escalation: 6 mg VB10.16 + Pembrolizumab

EXPERIMENTAL

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

Biological: VB10.16; Drug: Pembrolizumab

Phase 1: Dose Escalation: 9 mg VB10.16 + Pembrolizumab

EXPERIMENTAL

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

Biological: VB10.16; Drug: Pembrolizumab

Phase 2: Arm A: VB10.16 (recommended Phase 2 Dose) + Pembrolizumab

EXPERIMENTAL

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.

Biological: VB10.16; Drug: Pembrolizumab

Phase 2: Active comparator ph 2, Arm B: Pembrolizumab Monotherapy

EXPERIMENTAL

Patients randomized to receive pembrolizumab monotherapy.

Drug: Pembrolizumab

Interventions

VB10.16 BIOLOGICAL

Intramuscular injection using a PharmaJet needle-free injection system

Phase 1: Dose Escalation: 6 mg VB10.16 + Pembrolizumab; Phase 1: Dose Escalation: 9 mg VB10.16 + Pembrolizumab; Phase 2: Arm A: VB10.16 (recommended Phase 2 Dose) + Pembrolizumab; Phase1: Dose Escalation: 3 mg VB10.16 + Pembrolizumab

Pembrolizumab DRUG

Intravenous infusion.

Also known as: KEYTRUDA®

Phase 1: Dose Escalation: 6 mg VB10.16 + Pembrolizumab; Phase 1: Dose Escalation: 9 mg VB10.16 + Pembrolizumab; Phase 2: Active comparator ph 2, Arm B: Pembrolizumab Monotherapy; Phase 2: Arm A: VB10.16 (recommended Phase 2 Dose) + Pembrolizumab; Phase1: Dose Escalation: 3 mg VB10.16 + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nykode Therapeutics ASA: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (12)

CRLC Val d'Aurelle - Institut de Recherche en Cancerologie de Montpellier (IRCM)

Montpellier, 34298, France

RECRUITING

Institut Gustave Roussy

Paris, France

RECRUITING

Universitaetsklinikum Giessen und Marburg GmbH - Klinik fuer Hals, Nasen- und Ohrenheilkunde

Giessen, Germany

RECRUITING

National Institute of Oncology

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

Hospital del Mar

Barcelona, Spain

RECRUITING

ICO Hospitalet (Hospital Duran i Reynals)

Barcelona, Spain

RECRUITING

MD Anderson Cancer Center

Madrid, Spain

RECRUITING

East and North Hertfordshire NHS Trust Mount Vernon Hospital

London, United Kingdom

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Recurrence; Neoplasm Metastasis

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes

Study Officials

• Åse Bratland, MD, PhD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chief Medical Officer

CONTACT

+47 22 95 81 93; roliveri@nykode.com

Senior Clinical Trial Manager

CONTACT

cjaeger@nykode.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose-finding trial, including a dose escalation phase (phase 1) where participants are allocated sequentially to one of the 3 escalating doses; and a dose expansion phase (phase 2a) where participants are randomized to one of two doses.

Study Record Dates

• First Submitted: August 24, 2023
• First Posted: August 30, 2023
• Study Start: December 19, 2023
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): December 1, 2030
• Last Updated: August 26, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

NO (2); GB (1); FR (2); ES (3); HU (1); PL (2); DE (1)