‘Game-changing’ clinical trial leads to further discoveries

Clinical researchers Associate Professor Con Tam and Dr Hang Quach have built a reputation as leaders in the field of haematology, and their contributions to clinical knowledge with their own discoveries have pharmaceutical companies taking notice.

A/Prof Tam and Dr Quach are key members of an international program that developed a new class of anti-cancer drug that has literally given a new lease of life for patients with what would previously be considered terminal blood cancer.

‘A number of blood cancers, including non-hodgkin’s lymphoma and chronic lymphocytic leukaemia (CLL), have origins in B-cells,’ A/Prof Tam says. ‘There is a protein named BTK that plays a crucial role in B-cell development, and studies in a class of drugs called BTK inhibitors have begun targeting these cells in adults.’

A/Prof Tam and Dr Quach became involved in the study of the first drug in this field, Ibrutinib, in 2012, after seeing a phase one trial presented at an international conference.

Dr Hang Quach and Associate Professor Con Tam

‘What struck us was how effective Ibrutinib was,’ A/Prof Tam says. ‘In attempting to find the toxic dose of the drug, it became apparent that there wasn’t one. What was even more remarkable was that at anything apart from the lowest dose, all patients responded and the cancer shrunk away.

Patients that required transfusions no longer needed them and went back to work. Patients who had been given three to six months to live all of a sudden had a much brighter outlook.

‘We thought “wow, this is a gamechanger”, we need to get involved. We approached the company, Pharmacyclics, and said we have many needy Australian patients and we would love to make this drug accessible for clinical trials in Australia.’

‘We were invited to join the phase three study which compared Ibrutinib with an antibody, which was then the best standard of care in patients with advanced CLL. The response rate for the drug was ten times higher than that of the antibody and patients were three times more likely to survive.’

The results of this study were published in the New England Journal of Medicine. According to A/Prof Tam, there has seldom been a clinical trial so one-sided in medicine.

The team has since been involved with studies comparing Ibrutinib to the best standard of care in older patients who were not fit for chemotherapy. After overwhelming results proving its efficacy, Ibrutinib is now licenced in Europe, US and Australia.

A/Prof Tam and Dr Quach were Australia’s biggest recruiters to these studies. Three years later most of these patients are alive and working, after previously been given dismal outlooks. The team also made a number of observations on side-effects which has led to further discoveries.

A major side effect of Ibrutinib is bleeding, and the team found that this was because the drug inhibits platelets. In fact, BTK inhibitors may turn out to be quite effective cardiovascular drugs.

The team also made discoveries on another complication caused by the drug, an arrhythmia of the heart called atrial fibrillation.

Working with researchers right here in Melbourne, we were able to make new discoveries, and published three papers in Blood and Leukemia, the top ranked journal in Haematology.’

In 2013, the team began working with BeiGene Pharma, a company based in China, who had developed a second generation Ibrutinib drug. ‘BeiGene Pharma approached us due to our demonstrated expertise in BTK and our previous discoveries.’v

St Vincent’s is now a phase one site, along with Peter MacCallum Cancer Centre and Royal Melbourne Hospital, with A/Prof Tam acting as Principal Investigator overseeing the trial program which extends across US and Asia. ‘Australia is a much sought after destination for clinical trials.

We have highly trained medical staff and strong collaboration with lab and clinic staff. For example, we may never have found out about the bleeding side-effects of Ibrutinib if not for a close relationship between clinicians and lab researchers. ‘In America, that would be impossible, because platelets have a very short shelflife.

You only have an hour to test these samples and in institutions like the big American Cancer Centres, you’d be lucky if the samples could get to the pathology lab within three hours.’

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