Clinical Trials /

A Study of NG-641 and Pembrolizumab in Squamous Cell Carcinoma of the Head and Neck

NCT04830592

Description:

A multicentre, open-label, non-randomized, phase Ib neoadjuvant study of intravenous NG-641, as monotherapy or in combination with pembrolizumab, in patients with surgically resectable squamous cell carcinoma of the head and neck (SCCHN).

Related Conditions:
  • Hypopharyngeal Squamous Cell Carcinoma
  • Laryngeal Squamous Cell Carcinoma
  • Oral Cavity Squamous Cell Carcinoma
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of NG-641 and Pembrolizumab in Squamous Cell Carcinoma of the Head and Neck
  • Official Title: A Multicentre, Open-label, Dose-escalating, Phase Ib, Study of Intravenous Dosing of NG-641, as Monotherapy or in Combination With Pembrolizumab in Patients With Surgically Resectable Squamous Cell Carcinoma of the Head and Neck

Clinical Trial IDs

  • ORG STUDY ID: NG-641-02
  • NCT ID: NCT04830592

Conditions

  • Squamous Cell Carcinoma of the Head and Neck

Interventions

DrugSynonymsArms
NG-641Part A
PembrolizumabPart B

Purpose

A multicentre, open-label, non-randomized, phase Ib neoadjuvant study of intravenous NG-641, as monotherapy or in combination with pembrolizumab, in patients with surgically resectable squamous cell carcinoma of the head and neck (SCCHN).

Detailed Description

      Part A (NG-641 monotherapy): Up to 18 patients will be dosed with intravenous NG-641.
      Patients will then proceed to planned surgical resection.

      Part B (NG-641 and pembrolizumab): Up to 30 patients will be dosed with intravenous NG-641
      before receiving a single dose of pembrolizumab. Patients will then proceed to planned
      surgical resection.
    

Trial Arms

NameTypeDescriptionInterventions
Part AExperimentalNG-641 monotherapy
  • NG-641
Part BExperimentalNG-641 and pembrolizumab
  • NG-641
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          1. Newly diagnosed or recurrence of clinical stage III-IVb histologically confirmed oral
             cavity, larynx, hypopharynx or oropharynx squamous cell carcinoma of the head and neck
             (SCCHN)

          2. Disease is considered resectable, definitive surgery is planned in the next 8 weeks
             from screening, and the patient is willing to undergo surgery

          3. Known human papillomavirus (HPV) status for oropharyngeal cancer

          4. Provide written informed consent to participate

          5. Aged 18 years or over

          6. Willing to consent to tumour biopsies at baseline

          7. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

          8. Ability to comply with study procedures in the Investigator's opinion

          9. Adequate renal function

         10. Adequate hepatic function

         11. Adequate bone marrow function

         12. Coagulation profile within the normal range

         13. Meeting the reproductive status requirements of the study

        Exclusion Criteria:

          1. Prior allogeneic or autologous bone marrow or organ transplantation

          2. Active infections requiring antibiotics, physician monitoring or recurrent fevers
             (>38.0˚C) associated with a clinical diagnosis of active infection. Active infection
             requiring systemic therapy within 1 week of the anticipated first dose of study drug.

          3. Active viral disease or positive test for hepatitis B virus using hepatitis B surface
             antigen test or positive test for hepatitis C virus (HCV) using HCV ribonucleic acid
             (RNA) or HCV antibody test indicating acute or chronic infection. Positive test for
             HIV or AIDS

          4. Patients who have active autoimmune disease that has required systemic therapy in the
             past 2 years, are immunocompromised in the opinion of the Investigator, or are
             receiving systemic immunosuppressive treatment

          5. Treatment with any COVID-19 vaccine in the 28 days before the first dose of NG-641,
             unless the vaccine is known to not be based on an adenoviral vector (e.g. messenger
             RNA (mRNA) vaccines)

          6. Treatment with any vaccine (including known non-adenoviral COVID-19 vaccines) in the 7
             days before first dose of NG-641

          7. History of clinically significant chronic liver disease

          8. History of clinically significant interstitial lung disease (including pneumonitis)

          9. History of prior Grade 3-4 acute kidney injury or other clinically significant renal
             impairment

         10. Use of the following antiviral agents: ribavirin, adefovir, lamivudine or cidofovir
             within 7 days prior to the first dose of study treatment; or pegylated interferon
             (PEG-IFN) in the 14 days before the first dose of study treatment

         11. Incomplete recovery from surgery, incomplete healing of an incision site or evidence
             of infection

         12. Any of the following in the 3 months before the first dose of study treatment: Grade 3
             or 4 gastrointestinal bleeding or risk factors for gastrointestinal bleeding,
             infectious or inflammatory bowel disease, pulmonary embolism or other uncontrolled
             thromboembolic event, history or evidence of haemoptysis, or significant
             cardiovascular or cerebrovascular event

         13. Any known coagulopathy

         14. Prior history of bowel obstruction, or infectious or inflammatory bowel disease in the
             3 months before the first dose of study treatment

         15. Major surgery or treatment with any chemotherapy, radiation therapy, biologics for
             cancer or investigational drug/therapy in the 28 days before the first dose of study
             treatment

         16. Other prior malignancy active within the previous 3 years, except for local or organ
             confined early stage cancer that has been definitively treated with curative intent,
             does not require ongoing treatment, has no evidence of residual disease and has a
             negligible risk of recurrence and is therefore unlikely to interfere with the primary
             and secondary endpoints of the study, including response rate and safety

         17. Tumour location/extent considered by the Investigator to present a significant risk of
             airway obstruction if tumour flare or necrosis were to occur (e.g. an initial increase
             in tumour size that may lead to intestinal, airway or ureter obstruction, or
             penetrating tumour infiltration of major blood vessels, or other hollow organs
             potentially at risk of perforation)

         18. Any serious or uncontrolled medical disorder that, in the opinion of the Investigator
             or the Medical Monitor, may increase the risk associated with study participation or
             study treatment administration, impair the ability of the patient to receive protocol
             therapy or interfere with the interpretation of study results

         19. Previous treatment with any other enadenotucirev-based therapy, or fibroblast
             activation protein (FAP) targeting agent

         20. Known allergy/immune-related adverse reactions to NG-641 transgene or immune
             checkpoint inhibitor products or formulation; severe hypersensitivity to another
             monoclonal antibody

         21. Any other medical or psychological condition that would affect the patient's ability
             to comply with all visits and assessments, or compromise ability to give informed
             consent

         22. Related to or a dependent of the site staff, or a member of the site staff
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events (safety and tolerability)
Time Frame:End of Study Treatment Visit (Day 57)
Safety Issue:
Description:Assess the safety and tolerability of NG-641 by review of adverse events (AEs), serious adverse events, AEs resulting in delays to planned surgery, AEs leading to study treatment or study discontinuation and AEs resulting in death.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:PsiOxus Therapeutics Ltd

Trial Keywords

  • Squamous cell carcinoma of the head and neck
  • SCCHN
  • NG-641
  • Pembrolizumab

Last Updated

April 9, 2021