A new targeted drug, ozekibart, has halted the progression of advanced bowel cancer in 87 per cent of patients in an early trial, offering hope to those with few remaining treatment options. The phase I study, led by the Royal Marsden NHS Foundation Trust, combined the drug with Folfiri chemotherapy in 45 patients whose disease had worsened after two or three prior treatments and who were not eligible for surgery.
Results presented at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago showed that tumours shrank in 20 per cent of participants. In one case, a follow-up scan revealed no visible tumour. Dr Hazel Lote, a consultant medical oncologist at the Royal Marsden and honorary appointee at the Institute of Cancer Research, London, said: “These early results are promising for patients with advanced colorectal cancer who have very few treatment options left. The combination of ozekibart plus Folfiri not only shrank tumours in some patients, but stopped the cancer from worsening in many others, suggesting this treatment combination could offer a promising new treatment option.”
The objective response rate of 20 per cent compares favourably with historical response rates of between 1 and 6 per cent for current late-line therapies. Median progression-free survival was 5.5 months, with 42 per cent of patients remaining progression-free at six months. The disease control rate – meaning the cancer stopped growing – reached 87 per cent. Importantly, responses were observed irrespective of whether the tumour carried mutations in RAS or RAF genes, which often limit the effectiveness of other treatments.
How ozekibart targets cancer cells while sparing healthy tissue
Ozekibart, also known by its research name INBRX‑109, is a tetravalent death receptor 5 (DR5) agonist antibody. It works by mimicking a natural protein that binds to DR5 receptors on the surface of cancer cells, triggering a pathway that leads to programmed cell death – apoptosis. The drug is designed to exploit tumour-biased cell death signalling, meaning it preferentially activates the death pathway in cancer cells while largely leaving healthy tissue untouched. This selectivity is what makes the approach particularly promising, as conventional chemotherapy can damage healthy cells and cause severe side effects.
The safety profile of the combination therapy proved manageable, consistent with the known toxicities of Folfiri chemotherapy alone. Common treatment-related adverse events included diarrhoea, fatigue and nausea, which were predominantly grade 1 or 2 in severity. Notably, no significant liver toxicity was observed, despite a high prevalence of baseline hepatic metastases among trial participants.
Ozekibart has already shown clinical activity in other malignancies. A previous phase 2/3 trial, known as ChonDRAgon, met its primary endpoint for progression‑free survival in conventional chondrosarcoma, and a phase 1 trial in Ewing sarcoma reported a 64.5 per cent objective response rate when ozekibart was added to chemotherapy. The US Food and Drug Administration (FDA) granted ozekibart Fast Track and Orphan Drug designations for chondrosarcoma, and a Biologics License Application for that indication was submitted to the FDA in April 2026. A partial clinical hold on earlier trials was lifted by the FDA in April 2023.
Patient testimony and wider context
Among those to benefit was Amanda Burgess, a 59‑year‑old from East Sussex who joined the trial in July 2025. Diagnosed with bowel cancer in April 2024, she had surgery to remove the tumour but later learned the cancer had spread. “Chemotherapy and immunotherapy followed, but unfortunately they weren’t successful,” she said. “This new treatment has given me a new lease of life. Since starting the trial, I’ve had two significant reductions in the size of my tumour and things are now stable. The chemotherapy has been hard at times, but I’ve had no side effects from the trial drug itself. My energy has returned, and I’m back to doing the things I love. I walk my black labs Cromwell and Pip every day, I’m playing tennis, attending Pilates classes and spending time with my husband, David, and our children. I feel incredibly fortunate to be on the trial.”
Bowel cancer is the fourth most common cancer in the United Kingdom, with more than 48,000 new cases diagnosed each year. It is the second biggest cause of cancer deaths, claiming around 17,700 lives annually. The trial is being supported by the Bowelbabe Fund for Cancer Research UK, established by Dame Deborah James, who died from the disease in June 2022 at the age of 40. The fund has raised over £21 million for cutting‑edge research, early detection, personalised medicine and awareness campaigns.
Looking ahead, Inhibrx Biosciences – the company developing ozekibart – plans to engage with the FDA in the second half of 2026 to discuss initiating a first‑line registrational trial in colorectal cancer. It is also exploring potential accelerated approval pathways for ozekibart in fourth‑line colorectal cancer and Ewing sarcoma. A phase 1/2 trial (NCT03715933) with expansion cohorts for colorectal cancer and Ewing sarcoma continues to recruit. Dr Lote said the findings “are really encouraging” and support further research.