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: 51
• Locations: 8 countries
• Sites: 17

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: a phase 1, dose escalation part, testing 3 different doses of VB10.16 in combination with a standard fixed dose of pembrolizumab. The goal of this part 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. In the second part of the trial, a phase 2a, dose expansion part, participants will receive either the highest safe dose of VB10.16 from part 1 or the 3 mg dose both in combination with pembrolizumab. The dose given to each participant will be decided in random. The trial is designed to define the optimal dose of VB10.16 in combination with pembrolizumab for future clinical studies based on the safety, tolerability and anti-tumor effect data generated.

Conditions

HPV Positive Oropharyngeal Squamous Cell Carcinoma; HNSCC

Keywords

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

Outcome Measures

Primary Outcomes (7)

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

  Proportion of patient with Dose Limiting Toxicities (DLTs).

  42 days

• Phase 2: Dose Expansion: AEs

  Proportion of patients with AEs following treatment initiation by severity grade.

  12 months

• Phase 2: Dose Expansion: Discontinuation due to adverse reaction

  Proportion of patients who discontinue due to an adverse reaction.

  12 months

• 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.

  12 months

• Phase 2: Dose Expansion: Immune response

  Change from baseline in HPV16 E6/E7-specific T-cell responses as measured by IFN-γ ELISpot in post-vaccination samples.

  12 months

• Phase 1+2: Full trial: 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 (BOR) per RECIST 1.1.

  12 months

• Phase 1+2: Full trial: 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.

  24 months

Secondary Outcomes (29)

• Phase 2: Dose Expansion: Disease control rate (DCR)

  12 months

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

  12 months

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

  24 months

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

  12 months

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

  12 months

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: Dose Expansion: High dose of VB10.16 + Pembrolizumab

EXPERIMENTAL

The highest dose of VB10.16 to be safety-cleared in the escalation phase will be given 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: Dose Expansion: 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

Interventions

VB10.16 BIOLOGICAL

Intramuscular (i.m.) administrations of VB10.16 every 3 weeks (Q3W) starting at Week 1/Day 1 during a 12-week induction period, followed by a maintenance period with administrations every 6 weeks (Q6W) from Week 13 until Week 48. A total of up to 10 i.m. administrations will be given. VB10.16 will be administered via Pharma Jet® Stratis 0.5 mL needle free injection system.

Phase 1: Dose Escalation: 6 mg VB10.16 + Pembrolizumab; Phase 1: Dose Escalation: 9 mg VB10.16 + Pembrolizumab; Phase 2: Dose Expansion: 3 mg VB10.16 + Pembrolizumab; Phase 2: Dose Expansion: High dose of VB10.16 + Pembrolizumab; Phase1: Dose Escalation: 3 mg VB10.16 + Pembrolizumab

Pembrolizumab DRUG

Pembrolizumab 200 mg intravenous (i.v.) will be given in accordance with the local regulatory-approved label Q3W starting at Week 1/Day 1 for as long as the patient tolerates and continues to have clinical benefit from the treatment based on the patient and investigator's decision, up to a maximum of 35 treatments corresponding to approximately 2 years of treatment. After 48 weeks of treatment patients can continue on 200 mg Q3W or change to 400 mg Q6W at the discretion of the investigator and after consultation with the sponsor. Pembrolizumab will be given by i.v. infusion over 30 minutes.

Also known as: KEYTRUDA®

Phase 1: Dose Escalation: 6 mg VB10.16 + Pembrolizumab; Phase 1: Dose Escalation: 9 mg VB10.16 + Pembrolizumab; Phase 2: Dose Expansion: 3 mg VB10.16 + Pembrolizumab; Phase 2: Dose Expansion: High dose of VB10.16 + 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:

• GENERAL REQUIREMENTS
• ≥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
• 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
• ORGAN FUNCTION
• Overall function:
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1
• Hematological function:
• Platelets ≥100 × 10\^9/L (100,000/µL)
• Neutrophils (absolute neutrophil count \[ANC\]) ≥1.5 × 10\^9/L (1,500/µL)
• Hemoglobin ≥5.6 mmol/L (9.0 g/dL)
• Hepatic and hemostatic function:

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 molecule 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 VB10.16 treatment start
• Prior administration with a therapeutic HPV16 vaccine

Sponsors & Collaborators

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

Study Sites (17)

Fakultni nemocnice Olomouc, Olomuoc

Olomouc, Czechia

RECRUITING

Hôpital de la Pitié - Salpétrière in Paris

Paris, Paris, 75013, France

RECRUITING

Hospices Civils De Lyon

Lyon, France

RECRUITING

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

Montpellier, 34298, 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

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

+47 951 133 93; storhaug@nykode.com

Senior Clinical Trial Manager

CONTACT

+47 452 301 55; tolsen@nykode.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• 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): September 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: December 17, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (1); NO (2); GB (1); FR (4); ES (4); HU (1); PL (3); DE (1)