| Eligibility |
Inclusion Criteria:
1. Provide written informed consent to participate
2. Aged 18 years or over
3. Have one of eleven histologically or cytologically confirmed metastatic or advanced
carcinomas or adenocarcinomas that have progressed after at least one line of systemic
therapy and are incurable by local therapy
a. Tumour types eligible are: UC, SCCHN, MSI high/dMMR cancer, NSCLC,
uterine/endometrial cancer, cervical cancer, oesophageal cancer, gastric cancer,
cutaneous squamous cell carcinoma, HCC and TNBC
4. Additional tumour type specific criteria:
1. UC: carcinoma of the renal pelvis, ureter, bladder, or urethra that showed
predominantly transitional-cell features on histologic testing
2. SCCHN with oropharyngeal cancer: known HPV p16 status
3. MSI-high/dMMR cancer: MSI-high/dMMR status must be confirmed by an approved test
4. NSCLC: either squamous or non-squamous histology
5. Gastric cancer: gastric or gastroesophageal junction adenocarcinoma
5. All patients enrolled in combination therapy cohorts with check point inhibitor (dose
escalation and efficacy expansion phases) must have received prior treatment with a PD
1/PD-L1 inhibitor therapy (prior PD-1/PD-L1 may have been given as monotherapy or
combination therapy)
1. In combination dose-escalation, patients may have received a PD 1/PD L1 inhibitor
as part of any prior line of therapy (additional criteria apply when this is the
most recent line of therapy - see below)
2. In dose expansion cohorts, patients must have been treated with a PD 1/PD-L1
inhibitor as part of their most recent treatment
3. For all patients who received PD-1/PD-L1 inhibitor therapy as part of their most
recent line of treatment (includes dose-escalation and all patients in
dose-expansion), this must have been for a minimum of 6 weeks and maximum of 6
months, with best response of SD or PD - Patients with PD following treatment
with a PD-1/PD-L1 inhibitor as their most recent therapy must have a <50%
increase in disease burden
6. At least one measurable site of disease according to RECIST Version 1.1 criteria; this
lesion must be either (i) outside a previously irradiated area or (ii) progressive if
it is in a previously irradiated area
7. Tumour accessible for biopsy, biopsy deemed safe for biopsy by the Investigator, and
patient willing to consent to tumour biopsies
8. Ability to comply with study procedures in the Investigator's opinion
9. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
10. Predicted life expectancy of 6 months or more
11. Adequate lung reserve
12. Adequate renal function
13. Adequate hepatic function
14. Adequate bone marrow function
15. Coagulation profile within the normal range (international normalized ratio =1.5)
16. Meeting reproductive status requirements
Exclusion Criteria:
1. Prior or planned allogeneic 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. 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
5. 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
a. Patients with vitiligo, type I diabetes mellitus, asthma/atopy, residual
hypothyroidism due to autoimmune disease (which only requires hormone replacement
therapy), or conditions not expected to recur in the absence of an external trigger
are permitted to enrol providing they comply with the other eligibility criteria
relating to renal function. Use of inhaled corticosteroids, local steroid injection,
or steroid eye drops is allowed
6. Treatment with any live, live attenuated or COVID-19 vaccine in the 28 days before the
first dose of NG 350A
a. COVID-19 vaccines known not to be based on an adenoviral vector (e.g. mRNA
vaccines) are not subject to the 28-day exclusion (see exclusion criterion 7)
7. Treatment with any other vaccine (including known non-adenoviral COVID-19 vaccines) in
the 7 days before first dose of NG-350A
8. History of prior Grade 3-4 acute kidney injury or other clinically significant renal
impairment
9. History of clinically significant interstitial lung disease or non-infectious
pneumonitis
10. Lymphangitic carcinomatosis (clinically suspected or radiographic evidence)
11. Infectious or inflammatory bowel disease in the 3 months before the first dose of
study treatment
12. Myocardial infarction, stroke or other significant cardiovascular or cerebrovascular
event in the 12 months before the first dose of study treatment
13. Pulmonary embolism, deep vein thrombosis, or other uncontrolled thromboembolic event
in the 12 months before the first dose of study treatment, or current treatment with
therapeutic or prophylactic anticoagulation therapy
14. Grade 3 or 4 gastrointestinal bleeding (or risk factors for gastrointestinal bleeding)
or haemoptysis in the 3 months before first dose of study treatment, or any history of
bleeding requiring an investigative procedure (e.g. endoscopy), transfusion or
hospitalisation in the 12 months before the first dose of study treatment
15. Tumour location/extent considered by the Investigator to present a significant risk 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)
16. Use of the following prior therapies/treatments:
1. Treatment with any other anti CD40 antibody at any time
2. Treatment with an investigational or licensed 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.
Prior anti PD-1 / PD-L1 therapy is permitted without a 'washout' phase
3. Treatment with an investigational or licensed 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
4. 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
i. Bisphosphonate therapy or treatment with Receptor Activator of Nuclear factor
Kappa-B (RANK)-ligand inhibitors for metastatic bone disease is permitted
17. 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. Patients with toxicities (other than renal toxicities) attributed to
prior anti-cancer therapy that are not expected to resolve and result in long lasting
sequelae, such as neuropathy after platinum-based therapy, are permitted to enrol
18. Treatment with the 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
19. Known allergy/immune-related adverse reactions to NG-350A transgene or immune
checkpoint inhibitor products or formulation; severe hypersensitivity to another
monoclonal antibody
20. 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
21. Symptomatic brain metastases or any leptomeningeal metastases that are symptomatic
and/or require treatment. Patients with brain metastases are eligible if these have
been treated (surgery, radiotherapy). Both surgery and or radiotherapy must have been
completed at least 2 weeks before first dose of study treatment. There must also be no
requirement for immunosuppressive doses of systemic corticosteroids (>10 mg/day
prednisone equivalent) for at least 2 weeks before the first dose of study treatment
22. 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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