A new targeted therapy which uses radioactive material sourced from Australia’s Lucas Heights nuclear reactor has produced dramatic responses in some men with aggressive prostate cancer who have failed current therapies.

The treatment LuPSMA (Lutetium-177 PSMA-617) involves a radioactive molecule that is purpose made to bind to prostate cancer cells, enabling the targeted delivery of radiation to kill these tumours.

LuPSMA was also seen to reduce bone pain and improve quality of life in the proof-of-concept clinical trial which involved 30 patients – a world-first on this scale. Results of the Peter Mac-sponsored Phase II, single-arm study are published online today by Lancet Oncology.

Professor Michael Hofman, who led the trial at Peter Mac, says the responses were remarkable and supported starting a larger, randomised and multi-site trial of LuPSMA.

“Our small proof-of-concept trial shows that LuPSMA is highly active in men with aggressive prostate cancers, and it can trigger striking responses in some men,” says Prof Hofman.

“That LuPSMA was able to achieve this in men who have exhausted conventional treatment options is remarkable, and we now look forward with great interest and optimism to results of our Australia-wide TheraP trial now underway.”

The TheraP trial (ANZUP 1603) - which commenced once the positive results of Peter Mac’s proof-of-concept trial were known - is a partnership between ANZUP Cancer Trials Group Limited (ANZUP) and Prostate Cancer Foundation of Australia (PCFA).

The primary endpoint of Peter Mac’s proof-of-concept trial was whether LuPSMA could reduce PSA (Prostate Specific Antigen) levels by more than 50%. PSA is a blood biomarker for prostate cancer, so lowering PSA levels in men with advanced disease indicates a reduction in cancer activity.

After LuPSMA, all but one of the men saw a decline in PSA levels. More than half (57%, 17 of 30) showed at least a halving of their PSA levels - meeting the primary endpoint.  Notably, in six of the men (20%) exceptional responses were seen with PSA levels becoming close to undetectable. Full body scans also confirmed dramatic changes in men before and after receiving LuPSMA (see below).

“Some men also reported LuPSMA gave them rapid relief from otherwise severe bone pain and they had more energy for daily tasks and to enjoy their family time,” Prof Hofman says, noting the treatment was well tolerated with no immediate adverse effects and no treatment-related deaths.

LuPSMA is a personalised treatment using a concept called “theranostics”. This combines a diagnostic test and targeted therapy. First patients undergo a PSMA PET scan to see if the tumours “light up” reflecting adequate expression of the target. Only if suitable do they proceed with treatment. Peter Mac has a long history of expertise in theranostic therapies which enabled the team to perform this world-first study.

The Australian Nuclear Science and Technology Organisation (ANSTO) produces the Lutetium-177 required for LuPSMA in its OPAL research reactor.

“ANSTO produces a range of nuclear medicines used for diagnosis and treatment of a range of cancers, as well as heart, lung, liver and muscular-skeletal conditions, that one in two Australians need on average in their lifetime,” Mark Moore, General Manager at ANSTO Health says.

“ANSTO is proud to partner with the wider clinical community to develop potential new treatment options.”

Recruitment for the larger ANZUP/PCFA TheraP trial (ANZUP 1603) is underway with trial sites now open in Victoria, NSW and Queensland and soon to open in WA and SA.

ANZUP Chair, Professor Ian Davis, says ANZUP was delighted to work with Prof Hofman to launch this important study in partnership with PCFA and: “Clinical trials like this are the only way we can find out how well new treatments work, whether they are safe, and whether they should become the new gold standard for treatment in the future."

Read the paper published online by Lancet Oncology 

Reduced cancer activity observed in six men involved in Peter Mac’s proof-of-concept trial who recorded post-treatment PSA level declines of >96%. Red dots indicates sites of prostate cancer before (left side) and after (right side) treatment with LuPSMA.
Reduced cancer activity observed in six men involved in Peter Mac’s proof-of-concept trial who recorded post-treatment PSA level declines of >96%. Red dots indicates sites of prostate cancer before (left side) and after (right side) treatment with LuPSMA.

About LuPSMA

Scientists attach radioactive Lutetium-177 (Lu-177) to PSMA-617, a molecule that binds to Prostate Specific Membrane Antigen (PSMA) found on prostate cancer cells. When infused into the patient, it travels around the body attaching to and killing cancer cells. The radioactivity emitted from Lutetium travels only 1mm ensuring effects are confined to cancer cells with minimal impact on neighbouring healthy cells. The Lutetium-177 was supplied Australian Nuclear Science and Technology Organisation (ANSTO, Sydney). PSMA-617 is supplied by Endocyte (Indiana, USA).

About TheraP

TheraP (ANZUP 1603) is a randomised phase II trial of 177Lu-PSMA617 theranostic versus cabazitaxel chemotherapy in progressive metastatic castration resistant prostate cancer. This randomised study will compare Lu-PSMA with cabazitaxel, which is the standard treatment for advanced prostate cancer when other treatments have stopped working. Half the participants will receive Lu-PSMA and half will receive cabazitaxel. This study will provide further information about the risks and benefits of Lu-PSMA compared with cabazitaxel in men with prostate cancer. The study aims to enrol 200 participants in Australia. (More information about TheraP).

For more information or to arrange an interview please contact the Peter Mac Communications team on 0417 123 048.