Peter Mac scientists working with the drug company Senhwa Biosciences have developed a new way to target cancer, and have demonstrated it can stall disease progression in patients who are no longer responding to conventional treatments.
The experimental drug CX-5461 is the result of basic and pre-clinical laboratory research at Peter Mac and in collaboration with scientists at the John Curtin School of Medical Research.
Sixteen Peter Mac patients with various hard-to-treat blood cancers were involved in the Phase I trial, which was led by clinicians Dr Amit Khot and Assoc Prof Simon Harrison, and the results are published the latest edition of the journal Cancer Discovery.
CX-5461 works by effectively shutting down the production of ribosomes – the energy-making factories that cancer cells rely on to proliferate. In the trial, CX-5461 demonstrated clinical activity in a third of trial participants (6 of 16 patients).
“Our first-in-human trial showed CX-5461 can produce striking results in blood cancer patients who had otherwise developed resistance or were not responding to conventional treatments,” says Professor Rick Pearson, who is the head of the Research Program at Peter Mac that led the laboratory study.
‘These early positive results support moving to further clinical trials, involving a larger number of patients and targeting those cancers in which CX-5461 has shown the most potential.”
The trial participants had uncontrolled blood cancer. After treatment, one patient with anaplastic large cell lymphoma achieved a prolonged and clinically significant response. Five patients with myeloma, or diffuse large B-Cell lymphoma, saw a stabilisation of their disease.
The trial confirmed CX-5461 was safe at doses associated with a clinical benefit, and with manageable side effects.
CX-5461 is considered first in a potential new class of anti-cancer drugs that directly targets a critical part of the ribosome-making machinery - a protein called RNA Polymerase I – inside cancer cells.
“Many of our commonly used chemotherapy drugs can stop cells from dividing, but have significant side effects,” Prof Pearson says.
“CX-5461 is the first drug to stall cancer via a new mechanism, by targeting ribosomes, and our initial trial indicates this approach can be both effective and is well tolerated.
“This drug - the first of its kind to be given to patients, let alone show a clinical benefit - represents a paradigm-shift in the way we think about how cancer cells can be killed.”
The laboratory development of CX-5461 was also led by Prof Grant McArthur and Dr Gretchen Poortinga, at Peter Mac, and Prof Ross Hannan at Peter Mac and The John Curtin School of Medical Research, at the Australian National University.
The paper describing the trial results is titled “First-in-Human RNA Polymerase I Transcription Inhibitor CX-5461 in Patients with Advanced Hematological Cancers: Results of a Phase I Dose Escalation Study”。
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