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Chimeric steps up fight against deadliest brain cancer

Chimeric Therapeutics is building hope for brain cancer patients. Credit: File

Chimeric Therapeutics says it is a step closer to unlocking treatment hope for patients suffering from the world’s deadliest form of brain cancer after dosing its first patient as part of a phase-1B trial.

The new trial comes on the back of positive survival results in the previous phase of testing as the company continues to tackle the devastating glioblastoma condition with the development of its “CHM 1101” chimeric antigen receptor (CAR) T cell therapy.

Glioblastoma multiform (GBM) is a highly-aggressive and deadly cancer that often starts in the brain or spinal cord. It is fast-growing and has a poor survival rate – only about 40 per cent of patients remain alive in the first year after their diagnosis and just 17 per cent the following year.

Chimeric today revealed it had dosed its latest trial patient as a second line of therapy at the Sarah Cannon Transplant & Cellular Therapy Program within St. David’s South Austin Medical Center in Austin, Texas. It follows initial positive data from its phase-1A trial on patients treated with the first two dose levels.

More than half of the cancer fighter’s participating patients extended their median survival expectations up to 10 months, with two patients demonstrating survival beyond 14 months. Three of the patients are still alive and in follow up treatment.

Chimeric Therapeutics managing director and chief executive officer Jennifer Chow said: “We are thrilled to have reached this key milestone for Chimeric and the advancement of the CHM 1101 clinical development program. We believe that the full potential of CHM 1101 for patients with recurrent and/ or progressive glioblastoma will only be unlocked through the advancement of our clinical development program and we look forward to continuing to advance this trial forward.”

The CHM 1101 trial is being conducted under a United States investigational new drug application which has been designed as a two-part clinical trial that includes a dose confirmation trial and dose expansion testing.

If the dose confirmation trial proves successful, the study will advance to evaluate dose expansion. A further positive outcome will see the company design and initiate a registration trial, in collaboration with global regulatory feedback.

Chimeric managing director and chief medical officer Jason Litten said the company wanted to now build on the positive results from the phase-1A trial by advancing the clinical development of its “unique and potentially transformative cell therapy for patients with this devastating disease”.

The company says the phase-1A trials featured heavily pre-treated patients who received CHM 1101, on average, as a fourth line of therapy and demonstrated a 55 per cent disease control rate.

GBM is the most common and most aggressive primary brain tumour. More than 300,000 new cases are diagnosed globally, leading to some 250,000 deaths each year – a heartbreaking reality for patients and their families suddenly hit with a diagnosis. Patients with recurrent GBM have a poor prognosis, with limited treatment options and a median survival of less than a year.

Previous attempts to treat GBM with CAR T cells have been limited by tumour diversity. But chlorotoxin (CLTX)-directed CAR T cells in mice have shown broad anti-tumour activity and prolonged survival with no off-tumour toxicity or antigen escape.

CLTX is a small, basic peptide first isolated from scorpion venom and named for its ability to block chloride channels and cause neurotoxicity chlorotoxin. It selectively binds to a great proportion of malignant glioma cells, tumours and constituent tumour cells.

CAR T cells using CLTX as the targeting domain have been shown to mediate potent anti-GBM activity and efficiently target tumours lacking the expression of other GBM-associated antigens.

Now the world is waiting to see if Chimeric’s new trial phase can strike a new blow against a deadly condition that is currently leaving behind a trail of heartbreak.

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