Active Cancer NIHR-supported project Digestion, Kidneys & Other Organs

A multicentre, open-label, non-randomized, phase 1b trial of NG-350A, a tumour-selective anti-CD40-expressing adenoviral vector, in combination with chemoradiotherapy in locally advanced rectal cancer

In plain English

AI plain-English summary

A genetically engineered virus will be injected into patients with locally advanced rectal cancer, where it is designed to infect only tumour cells and force them to produce an immune-stimulating antibody. This matters because rectal cancer often resists standard chemoradiotherapy, and current treatments fail to achieve a complete response in many patients. The experimental therapy, NG-350A, aims to turn the tumour itself into a factory for an anti-CD40 antibody that activates the immune system to attack the cancer. The virus also kills cancer cells directly while leaving normal cells unharmed. If successful, this approach could transform how locally advanced rectal cancer is treated. Instead of relying solely on chemoradiation, patients might receive a single targeted viral injection that boosts their own immune response against the tumour. The trial will test whether combining NG-350A with standard therapy increases the proportion of patients who achieve a complete response within 12 to 36 weeks. It will also track side effects and long-term outcomes over up to three years. A positive result could lead to larger trials and eventually a new treatment option that reduces the need for surgery or prevents recurrence.

View original technical description
Worldwide, almost 10 million deaths in 2020 were estimated to be due to cancer. Despite the introduction of multiple new therapies, the overall burden of cancer incidence and mortality is growing worldwide and there remains a critical need for new and effective treatments.NG-350A is an experimental gene therapy medicinal product derived from a virus. The added gene is information in the form of deoxyribonucleic acid (DNA) required for making proteins or other molecules. This additional drug is called an ‘anti-CD40 antibody’ and is designed to help the immune system to attack cancer cells:1. The virus (study drug) infects only tumour cells2. The virus (study drug) forces tumour cells to produce another drug (anti-CD40 antibody)3. This additional drug is designed to help activate the immune system4. Activated immune cells then further attack the cancer cells.NG-350A can multiply in and kill cancer cells, but it is not expected to have an effect on normal cells.The study will include approximately 30 patients with locally advanced rectal cancer (LARC) that will all receive NG-350A. The trial is designed so that the initial anti-cancer effect of NG-350A plus standard chemotherapy and radiotherapy can be tested during a short active study treatment period of 12 weeks, while hospital sites can give additional standard-of-care treatment during the trial follow-up period. The study will determine the number of patients that achieve a complete response in 12, 18 and 36 weeks after starting NG-350A. The study will also investigate what side effects people have and what percentage of people experience these. The estimated duration of follow up during the study from joining to the end is at least 1 year up to a maximum follow-up of three years.

Researchers

Maria Hawkins (Principal Investigator)

Related Research

Grants with similar aims, by meaning.

FORTRESS - A multicentre, open-label, non-randomized, phase 1b trial of NG-350A, a tumour-selective anti-CD40-expressing adenoviral vector, in combination with chemoradiotherapy in locally advanced rectal cancer
FORTIFY:A multicentre, open-label, non-randomized, phase 1a/1b study of NG 350A, a tumour-selective anti-CD40-expressing adenoviral vector, in combination with pembrolizumab in patients with metastatic or advanced epithelial tumours
Exploratory development of NG-350A for a Phase 1b expansion cohort clinical trial
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Original classification

Cancer

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