| Eligibility |
Inclusion Criteria:
Phase 1a:
- Histologically or cytologically documented metastatic or advanced epithelial cancer that
has relapsed from or is refractory to standard treatment, or for which no standard
treatment is available
All patients
1. Provide written informed consent to participate
2. At least one measurable site of disease according to RECIST Version 1.1 criteria
3. Tumour accessible for biopsy, biopsy deemed safe by the Investigator, and patient
willing to consent to tumour biopsies
4. Ability to comply with study procedures in the Investigator's opinion
5. Aged 18 years or over
6. ECOG performance status 0 or 1
7. Predicted life expectancy of 6 months or more
8. Adequate lung reserve
9. Adequate renal function
10. Adequate hepatic function
11. Adequate bone marrow function
12. Meeting reproductive status requirements
Exclusion Criteria:
1. Prior or planned allogenic or autologous bone marrow or organ transplantation
2. Splenectomy
3. Active infections requiring antibiotics, physician monitoring or systemic therapy
within 1 week of the anticipated first dose of study drug, or recurrent fevers
(>38.0°C) associated with a clinical diagnosis of active infection
4. Treatment with the antiviral agents: ribavirin, adefovir, lamivudine, cidofovir or
paxlovid within 10 days prior to the first dose of study treatment; or pegylated
interferon in the 4 weeks before the first dose of study treatment
5. Known history of hepatitis B infection or known active hepatitis C infection. Known
history of HIV infection
6. Patients who have active, known or suspected 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
7. Treatment with any live, live-attenuated or COVID-19 vaccine in the 28 days before the
first dose of NG-641
8. Treatment with any vaccine (including known non-adenoviral COVID-19 vaccines) in the 7
days before the first dose of NG-641
9. History of prior Grade 3-4 acute kidney injury or other clinically significant renal
impairment
10. History of clinically significant interstitial lung disease or non-infectious
pneumonitis
11. Lymphangitic carcinomatosis
12. Infectious or inflammatory bowel disease in the 3 months before the first dose of
study treatment
13. Any known CTCAE Grade =2 coagulation abnormality/coagulopathy
14. Any clinically significant cardiovascular, peripheral vascular, cerebrovascular, or
thromboembolic event in the 6 months before the first dose of study treatment
15. Grade 3 or 4 gastrointestinal bleeding All toxicities attributed to prior anti-cancer
therapy (including radiation therapy) other than alopecia must have resolved to Grade
1 or baseline before the first dose of study treatment
16. Tumour location/extent considered by the Investigator to present a significant risk if
tumour flare or necrosis were to occur
17. Known retinopathy, including retinal haemorrhages, cotton wool spots, papilloedema,
optic neuropathy and retinal artery or vein obstruction
18. Active clinically severe depression
19. Use of following prior therapies
- Enadenotucirev-based therapy, or a fibroblast activation protein (FAP) targeting
agent anytime
- Anti-cancer monoclonal antibody (mAb), immune checkpoint inhibitor, immune
stimulatory treatment or other biological therapy in the 28 days prior to the
first dose of study treatment (PD-1 / PD-L1 therapy permitted without a 'washout'
phase)
- Chemotherapy, targeted small molecule or other investigational drug in the 14
days or five half-lives (whichever is shorter) before the first dose of study
treatment
- Major surgery in the 28 days before the first dose of study treatment or
radiation therapy in the 14 days before the first dose of study treatment
- Bisphosphonate therapy or treatment with Receptor Activator of Nuclear factor
Kappa-? (RANK)-ligand inhibitors for metastatic bone disease is permitted
20. All toxicities attributed to prior anti-cancer therapy (including radiation therapy)
other than alopecia must have resolved to Grade 1 or baseline before the first dose of
study treatment
21. Known allergy/immune-related adverse reactions to NG-641 transgene or immune
checkpoint inhibitor products or formulation; severe hypersensitivity to another
monoclonal antibody
22. Known hypersensitivity to both cidofovir and valacyclovir
23. Other prior malignancy active within the previous 3 years (see protocol for
exceptions)
24. Symptomatic brain metastases or any leptomeningeal metastases that are symptomatic
and/or requires treatment
25. 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
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