Immunotherapy drug shows lack of promise in Phase 3 clinical trial for glioblastoma patients

Last week Bristol-Myers Squibb announced the initial results from their Phase 3 clinical trial that was assessing the effectiveness and safety of the immunotherapy drug Nivolumab in patients with recurrent glioblastoma.

Glioblastoma tumours are the most common and aggressive brain tumours found in adults. With an average survival period of 12-18 months, new and more advanced treatments are urgently needed to prolong survival. The current standard treatment protocol is to remove as much of the tumour as possible, before chemotherapy and radiotherapy are given. However, if the tumour returns, current standard treatments lack efficacy in prolonging survival.

Unfortunately this trial did not show improved overall survival in patients who had this treatment when compared to patients who had a different type of treatment, called Bevacizumab. Bevacizumab is currently approved for use in recurrent glioblastoma patients in America but not in the UK.

This trial was assessing whether Nivolumab was effective in extending the survival of patients who had a glioblastoma recurrence against those who received Bevacizumab.

Fouad Namouni, M.D., Head of Oncology Development and Head of Medical, Bristol-Myers Squibb said, “Glioblastoma is a historically difficult disease to treatment and conventional treatment options have demonstrated limited responses.

“We remain steadfast in our pursuit of treatments for diseases with the highest unmet need and continue our work to determine how our Immuno-Oncology agents can potentially improve outcomes for these patients."

The full set of data will be presented on 7 May at the World Federation of Neuro-Oncology Societies (WFNOS) meeting in Zurich, Switzerland.

So how does Nivolumab work?

Nivolumab is a drug that is designed to uniquely harness the body's immune system to help it recognise and destroy tumour cells. Our immune systems depend on multiple checkpoints or 'immunological brakes' to avoid attacking healthy cells. Tumour cells often take advantage of these checkpoints to escape detection by the immune system. PD-L1 is an example of a checkpoint protein found on glioblastoma cells. Binding of PD-L1 to the protein PD-1 found on immune keeps the cells from killing the tumour cells in the body.

However, inhibiting a checkpoint protein using a drug such as Nivolumab releases the brakes on the immune system and can improve the ability of the immune system to respond to the tumour cells. This type of therapy has been shown to be effective in treating other cancers such as melanoma.

When it comes to the brain, immune-based treatments face a number of obstacles before they can even reach the tumour. One of the most significant challenges is the blood-brain barrier which protects the brain from harmful substances. Glioblastoma tumours are also very good at making immune suppressive environments around the tumour site to prevent immune cells attacking.

On the other hand, treatment advances for patients with glioblastoma have been rare which is why a lot of hope lies in immunotherapy treatments.

Although the results of this particular trial show that Nivolumab is not as effective when compared to Bevacizumab, other Phase 3 clinical trials are currently running testing the effectiveness of Nivolumab in newly diagnosed patients against standard therapy (radiotherapy and chemotherapy). The results of these trials will help researchers to identify whether the drug may suitable for a different subset of patients i.e. those who are newly diagnosed.

Dr David Jenkinson, our Chief Scientific Officer said: "We are very disappointed to hear about the results of this specific clinical trial. We believe that a lot of promise lies in immunotherapy as a potential treatment for these aggressive tumours."

"Despite the fact that this trial hasn't shown nivolumab to be effective as a standalone treatment for patients with recurrent glioblastoma, there still lies hope in testing this drug in combination with other treatments, which is something that this trial did not do. Alongside this study, Bristol-Myers Squibb are also co-ordinating trials testing the effectiveness of using nivolumab as a first line treatment for newly diagnosed patients in combination with radiotherapy, with or without standard of care chemotherapy."

"We look forward to seeing the full set of results from these trials as we know only too well that many of those diagnosed with a brain tumour have few, if any, effective treatment options"