A new drug combination has halted bowel cancer progression in 87 per cent of patients with advanced disease, early trial results show, raising hopes for a novel treatment option where few exist.
Trial results show marked improvement over standard care
The Phase I/II trial, led by the Royal Marsden NHS Foundation Trust with the Institute of Cancer Research, London, involved 45 evaluable patients aged 29 to 77 with locally advanced or metastatic, unresectable colorectal cancer. All had seen their disease worsen after two or three prior lines of systemic therapy and were not eligible for surgery. Approximately 70 per cent received the combination as a fourth-line treatment, and 80 per cent had previously progressed on irinotecan-based regimens.
Patients received ozekibart alongside FOLFIRI chemotherapy — a standard regimen of folinic acid, fluorouracil and irinotecan. Tumours shrank in 20 per cent of participants, a significant improvement over the historical response rate of 1 to 6 per cent for similar late-line settings. Crucially, the cancer stopped growing in 87 per cent of patients, including those whose tumours stabilised. In one case, a follow-up scan revealed no visible tumour.
The median progression-free survival (PFS) for the evaluable group was 5.5 months. At the six-month landmark, 42 per cent of patients remained progression-free, with nine still on active therapy. Nearly half of the observed responses lasted more than six months. Notably, responses were seen regardless of RAS or RAF mutation status, suggesting potential activity across molecular subgroups.
Dr Hazel Lote, consultant medical oncologist at the Royal Marsden NHS Foundation Trust 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 findings are being presented at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.
How ozekibart targets cancer cells while sparing healthy tissue
Ozekibart is a precision-engineered, tetravalent death receptor 5 (DR5) agonist antibody developed by Inhibrx Biosciences, Inc. It works by mimicking a natural protein to bind specifically to DR5 receptors on the surface of cancer cells. This binding triggers a process of programmed cell death known as apoptosis. The drug’s tetravalent structure — meaning it has four binding sites — allows it to cluster DR5 receptors on cancer cells with high efficiency, delivering a potent signal for self-destruction.
This mechanism exploits the fact that the DR5 death pathway is often more sensitive in cancer cells than in healthy tissue. By aiming directly at this vulnerability, ozekibart can trigger cell death in tumours while largely sparing normal cells. Earlier DR5-targeting therapies had been limited by liver toxicity, but in this trial no significant liver toxicity was observed despite 68 per cent of patients presenting with liver metastases at baseline.
Ozekibart has previously demonstrated clinical activity in other malignancies. In a randomised, placebo-controlled Phase 2/3 trial in conventional chondrosarcoma — a rare bone cancer — involving 206 patients, ozekibart more than doubled median PFS to 5.52 months from 2.66 months, representing a 52 per cent reduction in the risk of disease progression or death. Those results supported a biologics license application (BLA) submitted to the US Food and Drug Administration in April 2026. Ozekibart received FDA Fast Track designation for chondrosarcoma in January 2021 and Orphan Drug designation in November 2021. The drug has also shown promise in relapsed or refractory Ewing sarcoma, with a Phase 1 expansion cohort reporting a 64.5 per cent objective response rate and an 87.1 per cent disease control rate.
‘A new lease of life’: patient testimony
Amanda Burgess, 59, from East Sussex, joined the trial in July 2025. She was diagnosed with bowel cancer in April 2024 and had surgery to remove the tumour, but was later told the cancer had spread. “Chemotherapy and immunotherapy followed, but unfortunately they weren’t successful,” she said. Since starting the ozekibart combination, she has experienced two significant reductions in the size of her tumour and her condition is now stable. “This new treatment has given me a new lease of life,” she said. “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.”
Safety profile and future directions
The combination of ozekibart plus FOLFIRI was generally well tolerated, with a safety profile broadly consistent with FOLFIRI chemotherapy alone. The most common treatment-related adverse events included anaemia, diarrhoea, nausea, fatigue and alopecia, most of which were low grade (Grade 1 or 2). Common side effects associated with FOLFIRI itself can include nausea or vomiting, heartburn, stomach cramps, changes in taste or smell, hair thinning, mouth sores, constipation, and sun sensitivity. More serious potential side effects include increased risk of infection, bruising, bleeding gums, nosebleeds, breathlessness and acute cholinergic syndrome related to irinotecan.
Inhibrx plans to discuss initiating a first-line registrational trial in colorectal cancer with the FDA in the second half of 2026. The company is also exploring potential accelerated approval pathways for ozekibart in fourth-line colorectal cancer and in refractory Ewing sarcoma.
Bowel cancer is the fourth most common cancer in the UK, 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 supported by the Bowelbabe Fund for Cancer Research UK, established by Dame Deborah James, who died in June 2022 at the age of 40 after campaigning tirelessly to raise awareness of the disease. The fund has raised millions to support research, clinical trials and awareness of bowel cancer symptoms, building on Dame Deborah’s legacy of breaking taboos and driving early detection.
