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

Inclusion Criteria:

1. Newly diagnosed or recurrence of clinical stage III-IVb, histologically confirmedoral cavity, larynx, hypopharynx or oropharynx SCCHN (T1 with N2-3; T2 with N2-3; T3with N0-3; T4a with N0-3)

2. Disease is considered resectable, definitive surgery is planned in the next 8 weeksfrom screening, and the patient is willing to undergo surgery (potential for 2-3 cmof 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 infectionrequiring 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 inthe past 2 years, are immunocompromised in the opinion of the Investigator, or arereceiving 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., mRNAvaccines)

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 renalimpairment

10. Use of antiviral agents

11. Incomplete recovery from surgery, incomplete healing of an incision site or evidenceof 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 uncontrolledthromboembolic event, history or evidence of haemoptysis, or significantcardiovascular or cerebrovascular event

13. Any known Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2coagulation abnormality/coagulopathy

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

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

• All toxicities attributed to prior anti-cancer therapy other than alopecia musthave resolved to Grade 1 or baseline before the first dose of study treatment.Patients with toxicities (other than renal toxicities) attributed to prioranti-cancer therapy which are not expected to resolve and result in long lastingsequelae, 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 riskof airway obstruction if tumour flare or necrosis were to occur

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

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

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

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

22. Related to or a dependent of the site staff, or a member of the site staff.