Brain cancer candidate heads vaccine news at ASCO

Positive survival data with Celldex’ Rintega in glioblastoma at the ASCO meeting in Chicago was a highlight of the cancer vaccine track.

Part of the buzz surrounding the brain cancer vaccine data probably stemmed from its target – the same disease that tragically claimed the life of Beau Biden, the son of US vice president Joe Biden – last month. However, the results speak for themselves with Rintega (rindopepimut) improving both overall survival, progression-free survival and the overall response rate to therapy when added to Roche’s Avastin (bevacizumab) in the phase II ReACT trial.

Glioblastoma is the most aggressive and lethal form of brain cancer, and there are currently few treatments to halt its progress.

28 per cent of the 73 total patients on Rintega/Avastin had not progressed after six months, compared to 16 per cent of those on Avastin alone. The vaccine also extended life by around two months, from 9.3 to 11.6 months and reduced the need for concomitant medications such as steroids, which are used to alleviate swelling in brain cancer.

Standard therapy for glioblastoma consists of surgical resection followed by concurrent chemo and radiotherapy with a median overall survival of 16 months. After 18 months’ follow-up, 30 per cent of patients on the combination were still alive, twice as many as on Avastin alone.

Rintega is a peptide vaccine that targets EGFRvIII, a version of the epidermal growth factor receptor (EGFR) that is expressed on a number of tumour cell types, and is now in a phase III trial. In February, the FDA granted the vaccine breakthrough status for the treatment of adult patients with EGFRvIII-positive glioblastoma.

Vaccines that encourage the immune system to respond to tumours have suffered a string of failures in late-stage testing, with researchers suggesting one reason may be the use of multiple mechanisms by cancer cells to evade detection.

That is one reason why there has been so much interest in combining checkpoint inhibitors, which switch off these evasion pathways, with each other and, indeed, with other forms of immunotherapy such as vaccines.

The first, and still only, cancer vaccine to be approved for marketing – Dendreon’s Provenge (now owned by Valeant) – did show efficacy in prostate cancer, but has been held back by complexities in making and delivering the therapy.

Celldex’ data suggests it may be able to break through the barriers restraining vaccines for cancer, and analysts have suggested commercial success could follow, with $400 million in sales potential as a treatment for glioblastoma recurrences, rising to $1 billion or more if it eventually gets approval for first-line use.

Rintega grabbed the headlines, but was not the only vaccine showing promise at ASCO. Phase II data on another glioblastoma candidate developed by Agenus, called HSPPC-96, was also presented at the conference and showed a survival benefit compared to standard therapy, with median progression-free survival of nearly 18 months.

Agenus’ approach is a bit more like Dendreon’s Provenge therapy as it requires tissue to be harvested during surgery to form the basis of the vaccine, and analysts have suggested Celldex’ off-the-shelf candidate may prove easier and cheaper to deliver.

Last year, a vaccine for glioblastoma based on dendritic cells and developed by Northwest Biotherapeutics, called DCVax-L, became the first drug to be approved for early access under the UK’s Promising Innovative Medicine (PIM) fast-track programme.

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