In short
NG-350A is an investigational oncolytic adenoviral vector designed to express an anti-CD40 antibody within tumours. It is being studied in patients with metastatic or advanced epithelial tumours. One registered trial (NCT05165433) has completed a Phase 1 evaluation of NG-350A in combination with pembrolizumab, enrolling 198 participants. A separate first-in-human study reported outcomes for 25 patients treated with NG-350A alone.
Key points
- NG-350A is a tumour-selective adenoviral vector engineered to express an agonist anti-CD40 antibody.
- The registered trial is a Phase 1 study in metastatic or advanced epithelial tumours.
- The trial enrolled 198 participants and has been completed.
- The primary focus of the trial was safety and tolerability, including dose-limiting toxicities.
- NG-350A was given by intravenous infusion in the registered combination trial.
- A first-in-human study reported NG-350A was well tolerated after intravenous and intratumoral dosing in 25 heavily pretreated patients.
What is NG-350A?
NG-350A is an investigational oncolytic adenoviral vector. It is a next-generation, blood-stable adenovirus that has been engineered to express an agonist anti-cluster of differentiation 40 (CD40) antibody while retaining tumour selectivity and oncolytic potency. The substance is not an authorised medicine; it remains under investigation in clinical trials. Oncolytic viruses are a class of cancer therapeutics that are designed to infect and destroy cancer cells while also stimulating an immune response against the tumour.
How does NG-350A work?
NG-350A is designed to work in two ways. First, as an oncolytic virus, it selectively infects and replicates within tumour cells, leading to their destruction. Second, the virus carries a transgene that encodes an agonist anti-CD40 antibody. CD40 is a receptor found on immune cells, and activating it can help remodel the immunosuppressive tumour microenvironment, potentially enhancing the immune system's ability to recognise and attack cancer cells. In a first-in-human study, transgene messenger RNA from replicating NG-350A was detected in 5 of 12 patients who received intravenous treatment and in 1 of 9 patients who received intratumoral injection, confirming that the virus can deliver its genetic payload within tumours.
Which conditions is it studied for?
- Metastatic or advanced epithelial tumours — cancers that arise from epithelial cells, which line the surfaces of organs and glands, and have spread to other parts of the body or are no longer amenable to curative treatment. This is the population studied in the registered Phase 1 combination trial.
How is NG-350A given?
In the registered combination trial, NG-350A was administered by intravenous infusion. The first-in-human study evaluated both intravenous and intratumoral administration. Intravenous dosing was given as infusions on Days 1, 3 and 5 of a 57-day treatment period across four dose levels; intratumoral dosing was given either as a single injection on Day 1 or as injections on Days 1, 8, 15 and 22.
What do the clinical trials show?
One registered clinical trial of NG-350A plus pembrolizumab is reported in the EU Clinical Trials Information System. The FORTIFY study is a Phase 1 trial that enrolled 198 participants with metastatic or advanced epithelial tumours and has been completed. The primary objective was to characterise the safety and tolerability of NG-350A in combination with pembrolizumab, including the incidence of adverse events, serious adverse events, adverse events leading to discontinuation, adverse events resulting in death, and dose-limiting toxicities. The trial also aimed to determine a recommended dose of NG-350A in combination with pembrolizumab for further development.
A separate first-in-human Phase Ia/Ib study (NCT03852511) evaluated NG-350A as a single agent in 25 heavily pretreated patients with metastatic or advanced epithelial tumours. Both intravenous and intratumoral dosing were reported to be well tolerated, with no evidence of transgene-related or off-target viral toxicity. Delivery of NG-350A to tumours was demonstrated in biopsy samples following both routes of administration, with a dose-dependent pattern seen with intravenous infusion and four patients remaining positive for vector DNA in biopsies at Day 57.
What side effects are known?
In the first-in-human study, intravenous and intratumoral dosing of NG-350A were both reported to be well tolerated, with no evidence of transgene-related or off-target viral toxicity. Both routes of administration induced anti-virus antibodies, although sustained persistence of NG-350A in blood samples was observed up to 7 weeks after the last dose, particularly with higher intravenous dose levels. Detailed side effect data from the registered combination trial have not been published in the provided sources.