Status and phase
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About
This study will evaluate the safety, tolerability and preliminary efficacy and also pharmacokinetics, immunogenicity and other pharmacodynamic effects to elucidate the mechanism of action of NG-350A, either alone or in combination with a check point inhibitor, in patients with advanced or metastatic epithelial tumours.
Full description
Phase Ia of this study is a dose escalation phase, investigating NG-350A administration by intravenous (IV) infusion, either alone or in combination with a check point inhibitor. Phase Ib of this study comprises of a Combination Dose Efficacy Expansion with NG-350A in combination with a check point inhibitor.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Provide written informed consent to participate
Aged 18 years or over
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
Additional tumour type specific criteria:
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)
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
Tumour accessible for biopsy, biopsy deemed safe for biopsy by the Investigator, and patient willing to consent to tumour biopsies
Ability to comply with study procedures in the Investigator's opinion
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Predicted life expectancy of 6 months or more
Adequate lung reserve
Adequate renal function
Adequate hepatic function
Adequate bone marrow function
Coagulation profile within the normal range (international normalized ratio ≤1.5)
Meeting reproductive status requirements
Exclusion criteria
Prior or planned allogeneic or autologous bone marrow or organ transplantation
Splenectomy
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
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
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
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)
Treatment with any other vaccine (including known non-adenoviral COVID-19 vaccines) in the 7 days before first dose of NG-350A
History of prior Grade 3-4 acute kidney injury or other clinically significant renal impairment
History of clinically significant interstitial lung disease or non-infectious pneumonitis
Lymphangitic carcinomatosis (clinically suspected or radiographic evidence)
Infectious or inflammatory bowel disease in the 3 months before the first dose of study treatment
Myocardial infarction, stroke or other significant cardiovascular or cerebrovascular event in the 12 months before the first dose of study treatment
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
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
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)
Use of the following prior therapies/treatments:
i. Bisphosphonate therapy or treatment with Receptor Activator of Nuclear factor Kappa-B (RANK)-ligand inhibitors for metastatic bone disease is permitted
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
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
Known allergy/immune-related adverse reactions to NG-350A transgene or immune checkpoint inhibitor products or formulation; severe hypersensitivity to another monoclonal antibody
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
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
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
Primary purpose
Allocation
Interventional model
Masking
28 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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