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).
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.
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