After the success of a previous clinical trial that used immunotherapy to target rare cancers, the team at the ONJCRI are conducting a second phase II trial to offer more patients a rare treatment option and try to find a biomarker to predict which patients respond to this treatment.


A cancer is considered rare if it affects fewer than six people per year per 100,000 of the population. This may seem like a small number, but collectively, these cancers account for around 20 per cent of all cancers diagnosed in Australia and worldwide. Despite this, individuals diagnosed with rare cancers often have limited treatment options and worse outcomes than those diagnosed with more common cancer types.

“There are very few clinical trials for rare cancers. Generally, you need a large number of patients to really see the benefit of treatments,” says Associate Professor Andreas Behren, Head of the Tumour Immunology Laboratory at the ONJCRI.

The two-year trial launched in 2021, will primarily target neuroendocrine cancers, biliary tract cancers, gynaecological cancers, and MSI-H cancers. Andreas explains that this Phase II clinical trial has come after the success of a previous trial led by Principal Investigator Professor Jonathan Cebon and Clinician-Scientist Dr Oliver Klein, who challenged the difficulty of running a rare cancer trial by using immunotherapy to target a variety of cancer types.

“Jonathan and Oliver basically grouped many rare cancers together for treatment. So, it didn’t matter if someone had cancer of the genital tract or of the GI tract, if it was a rare cancer than they were included in the study,” says Andreas.

“The trial was a huge success; response rates were higher than 30 per cent, which is unheard of in many of these types of cancers. But even better than the response rate was the fact that so many of the different cancer types responded.”

The current trial aims to confirm the efficacy of nivolumab combined with ipilimumab when tested on a larger number of patients with rare cancers while adding a new unique feature – genomic testing.  Under the direction of Professor David Thomas at the Garvan Institute, this testing will give patients and their clinicians valuable information about why the treatment is working in some patients and not in others and may guide future and more targeted treatment strategies.

“One of the key things we are now trying to do is find a biomarker which will allow us to predict if someone will respond to treatment in a more targeted way. In a perfect world, we would be able to use a biomarker to identify patients who will respond well to treatment via a blood test or other mechanism,” says Andreas.

Clinical Trials Manager Dr Jodie Palmer is excited by the possibilities and sees firsthand how these trials can change someone’s outcome.

“This trial will treat 240 participants from nearly every state in Australia, with a strong focus on regional sites. We are hopeful that the response rates will be higher than the first trial due to selecting more of the cancer types that responded previously, so for many of the patients this trial could be lifesaving, or at the least life extending.” She said.

Dr Oliver Klein, an immunologist and lead clinician for the trial, reiterates the impact that this trial may have for the future of rare cancers.

“It’s exciting that the MoST-CIRCUIT trial is part of a larger network that enables tumours to be sequenced so we can investigate if these tumours harbour any mutated genes. This might also allow us to use targeted agents to treat that particular mutation.” Says Oliver.

“So, you have immunotherapy that is working via the patient’s immune system, but also, if your tumour includes a mutated gene, there may be an option for dual targeting, so it is quite unique and has the potential to be game changing for patents.”


This trial is funded by the Minderoo Foundation, with tumour testing and financial support from OMICO via the MoST genomic cancer medicine program, and trial drugs provided as in-kind support by Bristol Myers Squibb.