ANZUP at ASCO 2025 – EVOLUTION

EVOLUTION

Background

Prostate cancer remains the most commonly diagnosed cancer in Australia and New Zealand with over 30,000 people expected to be diagnosed every year. Thanks to world class research, prostate cancer can be treated effectively for the majority of the people affected¹,². Nevertheless, over 4,000 people every year will die due to an advanced or hard-to-treat form of prostate cancer and many more people will have life-long treatment related side-effects including morbidity associated with long-term hormonal suppression, sexual dysfunction and mental health issues³. 

Metastatic castration-resistant prostate cancer (mCRPC) is a type of advanced prostate cancer that has spread to other parts of the body and no longer responds to standard hormone therapy, which is meant to lower testosterone. Even though testosterone levels are low, the cancer keeps growing. While it can’t be cured, there are several treatment options that can help slow the cancer down and manage symptoms.

About the trial

The aim of this study is to see if combining ipilimumab and nivolumab (drugs that activate the body’s own immune response to kill cancer cells), with Lu-PSMA (a type of treatment called radionuclide therapy that can be used to treat prostate cancer by bringing radioactive atoms into the cancer cells), can further improve the anti-cancer effects of Lu-PSMA. It is thought that ipilimumab and nivolumab and Lu-PSMA may work together to treat prostate cancer. Lu-PSMA can potentially kill cancer cells and break up the tumour into small pieces that may be recognised by your immune system while ipilimumab and nivolumab help activate the immune system to find and attack the cancer. This new treatment combination may lead to shrinkage or stabilisation of previously progressing tumours and therefore hopefully stop or reverse the growth of the cancer.

The EVOLUTION Trial is an investigator-initiated trial sponsored and led by ANZUP. This trial has received funding in partnership with the Prostate Cancer Foundation of Australia, Bristol Myers Squibb and Novartis. This trial is a collaboration between ANZUP, the NHMRC Clinical Trials Centre at the University of Sydney and the Australasian Radiopharmaceutical Trials Network (ARTnet) with support from MIM Software Inc. and ANSTO.

The EVOLUTION trial is now closed to recruitment and enrolled 93 people from across Australia.

Oral presentation at ASCO 2025

177 Lu-PSMA-617 with ipilimumab and nivolumab in metastatic castration-resistant prostate cancer (mCRPC): an investigator-initiated phase 2 trial

Prof Shahneen Sandhu reported the overall survival results of the EVOLUTION trial that showed the benefits of combining the radioligand therapy 177Lu-PSMA-617 (LuPSMA) and immunotherapy (nivolumab and ipilimumab) in hard-to-treat and metastatic castrate resistant prostate cancer. LuPSMA is now a standard of care for people affected by this disease, but all will eventually progress on treatment. The promising results showed that by 12 months, 33% of participants who received the combination were free of progressive disease compared to 17% if they received LuPSMA alone. Now, translational work is ongoing to understand the biology of response and to improve patient selection for this combination treatment.

References:

  1. Cancer Data in Australia, Australian Institute of Health and Welfare (AIHW) 2024
  2. New Zealand Cancer Registry (NZCR), Health New Zealand-Te Whatu Ora
  3. National Cancer Control Indicators; relative survival for prostate cancer by stage, 2011