World-First US Clinical Trial Opens for Glioblastoma Immunotherapy

A world-first clinical trial aimed at transforming the treatment of glioblastoma, the most aggressive form of brain cancer, has opened in the United States. The trial, dubbed GIANT (Glioblastoma Immunotherapy Advancement with Nivolumab and Relatlimab), will test whether immunotherapy drugs can help patients diagnosed with the lethal brain tumour.

Australian medical oncologist Professor Mustafa Khasraw, from Duke University in North Carolina, is leading the trial. Duke will join four other cancer centres in Los Angeles, San Francisco, Houston and New York in the two-stage trial.

The first stage will check the safety of the experimental treatment on a small number of newly diagnosed patients. The second will involve many more patients getting a random assignment of one or two immunotherapy drugs (Nivolumab and Relatlimab) before surgery, followed by combining them with more conventional treatments (radiotherapy and chemotherapy) after surgery.

The trial's foundation was laid by Professor Richard Scolyer, the 2024 Australian of the Year, who was diagnosed with IDH wild-type glioblastoma in mid-2023. Knowing it was incurable, colleague and medical oncologist Professor Georgina Long proposed trying what she had learnt successfully treating advanced melanoma patients with immunotherapy. Scolyer said: "Even if it knocked a few months off [my life], it was going to give some very important information quickly. That I’m still alive and functioning a long time after diagnosis certainly gives hope."

Scolyer was devastated when an operation revealed the tumour had returned last March, but he has defied expectations that he had just months to live. While he believes he has continued to deteriorate, he has been training for a charity bike ride in Tasmania next month, interrupted by fracturing two ribs when he fell while running.

Khasraw, the study principal investigator, said the GIANT trial was "team science" drawing together clinicians and scientists from many institutions around the world "to bring innovation and hope to patients". Three patients had been enrolled so far, with a fourth at the early screening stage.

While Khasraw hoped Scolyer would lead a very long life, he could not draw too many conclusions about his treatment from the fact that he is still alive. "I’m a scientist," he said. "I’m driven by data. In order to believe that something is truly effective, I need to see the clinical trial data." He considered the trial "absolutely a step in the right direction" for glioblastoma treatment.

Khasraw said he expected to know in about two years whether the treatment would be transformative. A peer-reviewed paper on the treatment developed by Long, published in the international journal Nature Medicine last year, laid the groundwork for the trial.

In Australia, the trial will be conducted by researchers at the Brain Cancer Centre, founded by radio presenter Carrie Bickmore after her husband Greg Lange’s death from brain cancer in 2011. The Australian leader will be Associate Professor Jim Whittle, a neuro-oncologist at Melbourne’s Peter MacCallum Cancer Centre. The trial will recruit only newly diagnosed glioblastoma patients, as immunotherapy is believed to have a better chance of working on tumours before they have been treated with radiotherapy or chemotherapy.

Khasraw said the trial would establish whether this approach is feasible or effective for the treatment of glioblastoma.