Status:

COMPLETED

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

Lead Sponsor:

Akamis Bio

Conditions:

Squamous Cell Carcinoma of the Head and Neck

Eligibility:

All Genders

18+ years

Phase:

PHASE1

Brief Summary

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 c...

Detailed Description

Part A (NG-641 monotherapy): Approximately 16 evaluable patients will receive three doses of IV NG-641 in Part A. Patients will then proceed to planned surgical resection. Part B (NG-641 and pembroli...

Eligibility Criteria

Inclusion

  • Newly diagnosed or recurrence of clinical stage III-IVb, histologically confirmed oral cavity, larynx, hypopharynx or oropharynx SCCHN (T1 with N2-3; T2 with N2-3; T3 with N0-3; T4a with N0-3)
  • Disease is considered resectable, definitive surgery is planned in the next 8 weeks from screening, and the patient is willing to undergo surgery (potential for 2-3 cm of resected tumour specimen to be available for translational research purposes)
  • Provide written informed consent to participate
  • Aged 18 years or over
  • Willing to consent to tumour biopsies at baseline
  • ECOG performance status 0 or 1
  • Ability to comply with study procedures in the Investigator's opinion
  • Adequate renal function
  • Adequate hepatic function
  • Adequate bone marrow function
  • Meeting reproductive status requirements

Exclusion

  • Prior allogeneic or autologous bone marrow or organ transplantation
  • 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
  • Active viral disease or positive test for hepatitis B virus, hepatitis C virus (HCV) or HIV/AIDS
  • 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 (see protocol for full criteria)
  • 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., mRNA vaccines)
  • Treatment with any vaccine (including known non-adenoviral COVID-19 vaccines) in the 7 days before first dose of NG-641
  • History of clinically significant chronic liver disease
  • History of clinically significant interstitial lung disease (including pneumonitis)
  • History of prior Grade 3-4 acute kidney injury or other clinically significant renal impairment
  • Use of antiviral agents
  • Incomplete recovery from surgery, incomplete healing of an incision site or evidence of infection
  • 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
  • Any known Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2 coagulation abnormality/coagulopathy
  • Prior history of bowel obstruction, or infectious or inflammatory bowel disease in the 3 months before the first dose of study treatment
  • 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:
  • • All toxicities attributed to prior anti-cancer therapy other than alopecia must have resolved to Grade 1 or baseline before the first dose of study treatment. Patients with toxicities (other than renal toxicities) attributed to prior anti-cancer therapy which are not expected to resolve and result in long lasting sequelae, such as neuropathy after platinum-based therapy, are permitted to enrol
  • Other prior malignancy active within the previous 3 years
  • Tumour location/extent considered by the Investigator to present a significant risk of airway obstruction if tumour flare or necrosis were to occur
  • 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
  • Previous treatment with any other enadenotucirev-based therapy, or fibroblast activation protein (FAP) targeting agent
  • Known allergy/immune-related adverse reactions to NG-641 transgene or immune checkpoint inhibitor products or formulation; severe hypersensitivity to another monoclonal antibody
  • 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
  • Related to or a dependent of the site staff, or a member of the site staff.

Key Trial Info

Start Date :

November 4 2021

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

October 4 2024

Estimated Enrollment :

36 Patients enrolled

Trial Details

Trial ID

NCT04830592

Start Date

November 4 2021

End Date

October 4 2024

Last Update

March 24 2025

Active Locations (4)

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Page 1 of 1 (4 locations)

1

Cardiff & Vale University LHB

Cardiff, United Kingdom

2

The Clatterbridge Cancer Centre

Liverpool, United Kingdom

3

The Royal Marsden Hospital

London, United Kingdom

4

University Hospital Southampton NHS Foundation Trust

Southampton, United Kingdom, SO16 6YD