Clinical Trial to Evaluate Opdivo, Opdualag in Glioblastoma

Following the results of a hypothesis-generating study of immunotherapy in glioblastoma, a type of brain cancer, a phase 2 clinical trial is set to evaluate Opdivo (nivolumab) with or without relatlimab, a combination known as Opdualag, among patients with isocitrate dehydrogenase (IDH)-wildtype newly diagnosed glioblastoma (ndGBM).

The GIANT trial, set to be held in the United States at Duke University in Durham, North Carolina, was designed by professor Georgina Long, following up on her research into glioblastoma that was published in Nature Medicine.

Long is the medical director of Melanoma Institute Australia (MIA), and chair of melanoma medical oncology and translational research at MIA and Royal North Shore Hospital, The University of Sydney. 

The Nature Medicine article looked at the case of one patient with IDH-wild-type, MGMT promoter unmethylated glioblastoma who received treatment with a single dose of triplet immunotherapy followed by surgery who, after 17 months, showed no definitive sign of recurrence.

“It really showed that despite what the oncology field thinks about glioblastoma, that the immune system is not able to be activated against it, you can actually do that in certain circumstances,” said Long. “So when I came up with the idea and the hypothesis, because I developed drugs in melanoma — yes, we are curing over 50% of patients with immune stimulants or immunotherapy, [but] we still have 45% of patients who die from melanoma, and they die quickly — from my experience in the translational lab and in the clinic, because I'm a medical oncologist and translational researcher, my thinking about those sort of patients and the resistance to immunotherapy is what I applied to the glioblastoma.”

In light of the findings, the GIANT trial has an estimated start date of June 1, 2025, and will enroll approximately 92 patients, according to its listing on clinicaltrials.gov.

Long discussed her findings and the upcoming GIANT trial in an interview with CURE.

Transcript:

So the principles are, first of all, choose the right immunotherapies. You need to use CTLA4. That's very important as part of your regimen in these terrible, terrible tumors. Number two, use it early. Immunotherapy is best if you're going to test it. Test it early. Number three, that publication, was hypothesis generating, we don't want to give false hope. We now need to show clinical benefit in a trial, and we are opening that. And in fact, I designed that within six weeks, and got the drugs within 10 weeks of that diagnosis of that patient. And then number four, the science showed activation of T cells, T cells infiltrating the glioblastoma after treatment and drug bound to the T cells. They're the four principles from that piece of work that I led, and now the trial should open in 2025 across America and Australia. It's an Australian trial driven by the Australians, but the Americans came on board, and now it's co led by Duke University and the [Walter and Eliza Hall Institute of Medical Research] and [Peter MacCallum Cancer Centre] in Australia, but that came from the work I did and I put together.

Transcript has been edited for clarity and conciseness.

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