search
Back to results

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

Primary Purpose

Squamous Cell Carcinoma of the Head and Neck

Status
Recruiting
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
NG-641
Pembrolizumab
Sponsored by
Akamis Bio
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Squamous Cell Carcinoma of the Head and Neck focused on measuring Squamous cell carcinoma of the head and neck, SCCHN, NG-641, Pembrolizumab, Akamis Bio

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. 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)
  2. 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)
  3. Provide written informed consent to participate
  4. Aged 18 years or over
  5. Willing to consent to tumour biopsies at baseline
  6. ECOG performance status 0 or 1
  7. Ability to comply with study procedures in the Investigator's opinion
  8. Adequate renal function
  9. Adequate hepatic function
  10. Adequate bone marrow function
  11. Meeting reproductive status requirements

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, hepatitis C virus (HCV) or HIV/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 (see protocol for full criteria)
  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., 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 antiviral agents
  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 Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2 coagulation abnormality/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:

    • 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

  16. Other prior malignancy active within the previous 3 years
  17. Tumour location/extent considered by the Investigator to present a significant risk of airway obstruction if tumour flare or necrosis were to occur
  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.

Sites / Locations

  • Cardiff & Vale University LHBRecruiting
  • The Clatterbridge Cancer CentreRecruiting
  • The Royal Marsden HospitalRecruiting
  • University Hospital Southampton NHS Foundation TrustRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Part A

Part B

Arm Description

NG-641 monotherapy

NG-641 and pembrolizumab

Outcomes

Primary Outcome Measures

Incidence of adverse events (safety and tolerability)
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.

Secondary Outcome Measures

Full Information

First Posted
March 31, 2021
Last Updated
June 21, 2023
Sponsor
Akamis Bio
search

1. Study Identification

Unique Protocol Identification Number
NCT04830592
Brief Title
A Study of NG-641 and Pembrolizumab in Squamous Cell Carcinoma of the Head and Neck
Acronym
MOAT
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 4, 2021 (Actual)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
October 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Akamis Bio

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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 carcinoma of the head and neck (SCCHN).
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 pembrolizumab): Up to 20 evaluable patients will receive three doses of IV NG-641 and one dose of pembrolizumab. Patients will then proceed to planned surgical resection.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Squamous Cell Carcinoma of the Head and Neck
Keywords
Squamous cell carcinoma of the head and neck, SCCHN, NG-641, Pembrolizumab, Akamis Bio

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Part A
Arm Type
Experimental
Arm Description
NG-641 monotherapy
Arm Title
Part B
Arm Type
Experimental
Arm Description
NG-641 and pembrolizumab
Intervention Type
Biological
Intervention Name(s)
NG-641
Intervention Description
Patients receive three doses of NG-641 by intravenous infusion. NG-641 is a replication competent adenoviral vector producing a bispecific T cell activator (TAc) targeting fibroblast activation protein (FAP) plus immune enhancer genes CXCL9/CXCL10/IFNa2. This can lead to killing of tumor cells and stimulation of immunity against the tumor cells.
Intervention Type
Biological
Intervention Name(s)
Pembrolizumab
Intervention Description
Patients receive three doses of NG-641 by intravenous infusion and a single dose of Pembrolizumab by intravenous infusion.
Primary Outcome Measure Information:
Title
Incidence of adverse events (safety and tolerability)
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.
Time Frame
End of Study Treatment Visit (Day 57)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Criteria: 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Akamis Bio
Phone
+44 (0)1235 835 328
Email
enquiries@akamisbio.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christian Ottensmeier, Prof.
Organizational Affiliation
The Clatterbridge Cancer Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cardiff & Vale University LHB
City
Cardiff
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mererid Evans, Dr
Phone
0292 0615888
Ext
6902
Facility Name
The Clatterbridge Cancer Centre
City
Liverpool
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christian Ottensmeier, Prof.
Phone
0151 7951475
Facility Name
The Royal Marsden Hospital
City
London
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kevin Harrington, Prof.
Phone
020 73528171
Facility Name
University Hospital Southampton NHS Foundation Trust
City
Southampton
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ioannis Karydis, Dr
Phone
0782 7643397

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs