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”.


For more information contact the Peter Mac Communications team on 0417 123 048.

About Peter Mac

Peter MacCallum Cancer Centre is one of the world’s leading cancer research, education and treatment centres globally and is Australia’s only public hospital solely dedicated to caring for people affected by cancer. We have over 2,500 staff, including more than 580 laboratory and clinical researchers, all focused on providing better treatments, better care and potential cures for cancer.

About Senhwa Biosciences

Senhwa Biosciences, Inc. (TPEx:6492), a leading clinical stage pharmaceutical company focusing on developing First in Class, Next Generation DNA Damage Response (DDR) therapeutics for patients with unmet medical needs in oncology. Headquartered in Taiwan, but with a vital operational base in San Diego, California, the Senhwa Team is well positioned to oversee the development of their compounds. Development currently focused on two lead products Silmitasertib (CX-4945) and CX-5461 with novel MOA and for multiple indications. CX-5461 is under human clinical trial for solid tumors including breast cancer conducted by Canadian Cancer Trials Group (CCTG) in Canada. Silmitasertib (CX-4945) currently is under multiple clinical trials for the treatment of cholangiocarcinoma, basal cell carcinoma and medulloblastoma.