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Nivolumab fails to meet its target

Nivolumab, an immunotherapy drug, has been unsuccessful in improving overall survival in a phase 3 clinical trial when tested in newly diagnosed glioblastoma with unmethylated MGMT

Nivolumab, an immunotherapy drug, has been unsuccessful in improving overall survival in a phase 3 clinical trial when tested in newly diagnosed glioblastoma with unmethylated MGMT

In disappointing news the pharmaceutical company, Bristol-Myers Squibb, recently announced that the phase 3 clinical trial called CheckMate-498 didn’t meet its overall survival target.

This trial was evaluating nivolumab plus radiation therapy compared to temozolomide plus radiation therapy in patients with newly diagnosed glioblastoma with unmethylated MGMT promoter.

We know that a cure can’t wait for people with brain tumours and the fact that nivolumab had reached Phase 3 trials gave us hope. Unfortunately during the rigorous testing that all new drugs go through, nivolumab didn’t live up to these hopes in this group of people.

Tests are still ongoing in another group of people so we’ll keep an eye out for more results.

We’ve put some more information about this trial below.

Glioblastoma is the most common primary, high-grade brain tumour occurring in adults. In the last decade, there have been no new drugs approved for clinical use to treat glioblastoma and as such there is an acute need for new treatments for this aggressive tumour.

Glioblastomas have a biomarker, called MGMT, which is often tested for because it sometimes predicts how well chemotherapy will work.

The MGMT gene is the code for a protein involved in DNA repair. Higher levels of this protein can mean that some chemotherapy drugs won’t be as effective because the protein fixes the damage the drugs create.

However, if the MGMT gene is methylated, or altered, there is less protein to repair DNA, which means the chemotherapy drugs have a better chance of killing the cancer cells.

In CheckMate-498, nivolumab was being tested in people who have a glioblastoma with unmethylated MGMT, where the need for new treatments is even more urgent.

Nivolumab is a checkpoint-inhibitor, a type of immunotherapy which ‘takes the brakes off’ the immune system, allowing the immune cells to target and destroy the tumour cells.

Nivolumab has been successfully used to treat other tumours like melanoma and some lung cancers.

A phase 3 clinical trial, like CheckMate-498, compares new treatments to the current gold standard treatment, in this case is temozolomide plus radiotherapy.

In order for a new drug to be approved and make it to the clinic, it must be better than the existing treatment.

One way that the potential new treatment is assessed is using ‘overall survival’, which refers to how long people live after receiving different treatments.

Furthermore, although nivolumab did not meet its overall survival target in newly diagnosed patients with unmethylated MGMT promoter, it’s still being tested in another phase 3 clinical trial in people newly diagnosed with a glioblastoma with methylated MGMT promoter.

Although this is a disappointing development, it is important that we don’t view this clinical trial as a ‘failure’ or ‘loss’. Important progress is made by learning from negative results, as they provide opportunities to better understand how the drug works, and can highlight any improvements in trial design and implementation for the future.

While it is sad news that nivolumab has not proven to be better than current standard of treatment for one group of people, it still is a step towards developing precision treatments for people with brain tumours.