BMS immunotherapy combo to be trialled for deadly brain cancer

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, significantly improving survival rates in melanoma. The 10-year melanoma-specific survival rate for patients with stage IV disease treated with combination ICIs has risen from less than 5% to 52%.

Now, a pioneering approach developed by Professor Georgina Long AO, a medical oncologist at the University of Sydney and Medical Director of the Melanoma Institute Australia, is set to be trialled for glioblastoma by researchers at the Brain Cancer Centre in Melbourne.

Drawing on her expertise in immunotherapy and melanoma research, Professor Long led the first documented use of neoadjuvant triple immunotherapy in glioblastoma. This innovative treatment combines three checkpoint inhibitors – BMS’ anti-PD-1 Opdivo (nivolumab), anti-CTLA-4 Yervoy (ipilimumab), and anti-LAG3 Opdualag (relatlimab) – administered before surgery to prime the immune system.

“My hypothesis was that we could administer combination immunotherapy as first-line treatment before surgery to boost the immune system and activate T-cells to target the brain tumour – an approach I had previously developed successfully in both stage 3 melanoma and melanoma that had spread to the brain,” said Professor Long.

“This has never been done before, and what this trial will do is establish whether this approach is feasible or effective for the treatment of glioblastoma.”

Within the next year, a clinical trial will commence to investigate first-line neoadjuvant combination checkpoint inhibitor therapy in newly diagnosed glioblastoma patients. The Phase 2 GIANT study will test the efficacy of dual immunotherapy (nivolumab and relatlimab), with some patients also receiving chemotherapy.

The Brain Cancer Centre, established in partnership with the Walter and Eliza Hall Institute of Medical Research (WEHI) and supported by the Victorian Government, will lead the trial. Professor Long has secured drug access for the study and is passing the baton to Dr Jim Whittle, a leading Australian neuro-oncologist at the Peter MacCallum Cancer Centre, The Royal Melbourne Hospital, and Co-Head of Research Strategy at the Brain Cancer Centre.

“I am delighted to be handing the baton to Dr Jim Whittle to commence a broader scientific study to scientifically determine if – and how – this process might work in treating glioblastoma,” Professor Long said. “While we are buoyed by the results of this experimental treatment so far, a clinical trial in a large group of patients would need to happen before anyone could consider it a possible breakthrough,” she added.

Dr Whittle emphasised the importance of rigorous trial design in translating early success into meaningful clinical outcomes.

“We are pleased to be able to build on this exciting work by diving into the process of designing a clinical trial, which takes time, care and accuracy. When that process is complete, the result will be a world-first clinical trial that enables us to thoroughly test the hypothesis against a representative sample of patients,” he said.

Glioblastoma remains one of the most aggressive and deadly cancers, with a median survival time of just 12 to 18 months. Only 25% of patients survive beyond one year, and fewer than 5% live beyond three years.

The forthcoming trial builds on Professor Long’s work in immunotherapy. Last week, she published a paper in The Lancet Oncology which detailed the development of a dual combination immunotherapy which has seen to a seven-year survival rate in 51 percent of patients with melanoma that had metastasised in the brain. The previous survival rate was 16 weeks.

If successful, the GIANT study could mark a significant step forward in the treatment of glioblastoma, offering new hope for patients facing this devastating disease.

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