First in Human Study With NG-641, a Tumour Selective Transgene Expressing Adenoviral Vector

About

Brief Summary

To characterise the safety and tolerability of NG-641 in patients with metastatic or advanced epithelial tumours.

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase I

Eligibility

Gender

All

Healthy Volunteers

Minimum Age

18 Years

Maximum Age

N/A

Inclusion Criteria:

Histologically or cytologically documented advanced or metastatic epithelial cancer that has relapsed from or is refractory to standard treatment, or for which no standard treatment is available
Provide written informed consent to participate
Aged 18 years or over
Tumour accessible for biopsy, biopsy deemed safe by the Investigator, and patient willing to consent to tumour biopsies
ECOG performance status 0 or 1
Predicted life expectancy of 6 months or more
Ability to comply with study procedures in the Investigator's opinion
Adequate lung reserve
Adequate renal function
Adequate hepatic function
Adequate bone marrow function
Coagulation profile within normal range and International Normalised Ratio ≤1.5, as appropriate
Meeting reproductive status requirements
Phase Ia - Dose Optimisation Phase only: at least one measurable site of disease according to RECIST Version 1.1 criteria

Exclusion Criteria:

Prior or planned allogenic or autologous bone marrow or organ transplantation
Splenectomy
Active infection within 1 week of the anticipated first dose of study drug that required antibiotics (or other systemic therapy), physician monitoring or was associated with recurrent fevers (>38.0˚C)
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
Treatment with any live, live-attenuated or COVID-19 vaccine in the 28 days before the first dose of NG-641
Treatment with any vaccine (including known non-adenoviral COVID-19 vaccines) in the 7 days before the first dose of NG-641
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
Infectious or inflammatory bowel disease in the 3 months before the first dose of study treatment
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
Tumour location/extent considered by the Investigator to present a significant risk if tumour flare or necrosis were to occur
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 in the 4 weeks before the first dose of study treatment
Grade 3 or 4 gastrointestinal bleeding
Pulmonary embolism, deep vein thrombosis, or other uncontrolled thromboembolic event in the 12 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
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.
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
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 requires treatment. Patients with brain metastases are eligible if these have been treated (surgery, radiotherapy)
Penetrating tumour infiltration of major blood vessels, pericardium, gastrointestinal tract or other hollow organs that may lead to perforation due to tumour necrosis
Patients at an increased risk due to tumour flare, as assessed by the Investigator (e.g. an initial increase in tumour size that may lead to intestinal obstruction, obstruction of the ureter or airway)
Previous treatment with enadenotucirev or FAP targeting agents
Known allergy to NG-641 transgene products or formulation
Any other medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent

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