Prof Ben Solomon and Nick Pavlakis, renowned leaders in lung cancer research, have secured a landmark $14,707,962 in funding for the “ASPiRATION-2 Liquid” (ASPiRATION 2L) clinical trial in the Medical Research Future Fund 2022 Frontier Health and Medical Research grant opportunity.
This pioneering project, in collaboration with University of Sydney and University of Melbourne, will place Australia at the forefront of global precision medicine by evaluating the use of serial liquid biopsies to revolutionise personalised lung cancer treatment.
Over the last decade, NSCLC treatment has been transformed by the discovery of several genomic mutations that drive tumour growth, and the development of targeted therapies to specifically target that mutation.
For patients with these forms of mutation-driven advanced stage NSCLC (oncogene-addicted NSCLC), treatment has changed from empirical treatments, such as chemotherapy, to daily tablets taken from home with tolerable side effects.
People that can be treated with these drugs have survived more than 10 years living with metastatic NSCLC. However, resistance to these targeted therapies is inevitable.
Over half of all NSCLCs have genomic alterations for which highly effective targeted treatments are currently available. Source: Thai, Solomon et al. The Lancet 2021
The ASPiRATION 2L study: Addressing resistance to targeted therapies
The ASPiRATION 2L trial, led by Chief Investigators Prof Ben Solomon (CIA) and Prof Nick Pavlakis (CIB), alongside a national team of esteemed researchers, will evaluate the use of serial liquid biopsies (sampling the blood to detect circulating tumour DNA (ctDNA)) to guide treatment decisions for 500 patients with advanced oncogene-addicted NSCLC that has become resistant to therapy.
Determining the tumour genomic profile that gives rise to resistance is an active area of research, but to date has relied on sampling tumour tissue through invasive tissue biopsy.
Resistance to earlier generation targeted therapies arose primarily through escape variants of the mutation driving tumour growth, but as targeted therapies have become more sophisticated, there is a growing body of evidence, including TOGA’s ALKTERNATE and OSCILLATE clinical trials, suggesting that resistance is now also dependent on co-mutations that constantly evolve during the course of treatment.
"The ASPiRATION-2L trial presents a unique opportunity to redefine personalised medicine for lung cancer using liquid biopsy with ctDNA to guide treatment decisions, not just at the time of diagnosis, but throughout the patient journey."
Liquid biopsy: The key to the personalised medicine revolution
ASPiRATION2L strives to develop a new model of personalised medicine in cancer where therapies are directed by serial sampling of the tumour genomic environment. While the patient may continue to have a burden of tumour, this is adequately controlled so it is possible to live with highly aggressive cancers, such as NSCLC, in a chronic disease-like state.
Liquid biopsy is less invasive and able to be undertaken more frequently to build an ongoing profile of the tumour genome. This enables more frequent feedback on how the tumour genome is responding to additional treatments.
This innovative approach that will be employed in ASPiRATION2L aims to revolutionise personalised medicine, moving away from empirical therapies, and introducing genomically-directed therapy. It is hypothesised that this approach will enable people to live with metastatic NSCLC in a chronic disease-like state with improved survival and quality of life, and reduce the use of costly, ineffective treatments.
The Chief Investigator Team
Building upon the success and infrastructure developed during the recently completed ASPiRATION program, co-led by Professors Solomon, Pavlakis, and David Thomas, the ASPiRATION 2L trial represents a significant advancement in lung cancer care.
The national team of Chief Investigators, including Prof Chee Lee, A/Prof Thomas John, Prof Sarah-Jane Dawson, Prof Sean Grimmond, Prof Stephen Fox, Dr Lisa Briggs, Prof Wendy Cooper, Prof Kate Sutherland, Prof Rachel Morton, A/Prof Venessa Chin, Dr Rebecca Tay, and Prof Michael Milward, brings together a wealth of expertise and geographical reach in lung cancer clinical care and ctDNA technologies.
The significance of ASPiRATION 2L
Lung cancer remains the leading cause of cancer death in Australia and worldwide. The ability to identify actionable gene alterations in tumour tissue has led to the development of highly effective targeted therapies, improving patient outcomes and reducing side effects. However, obtaining tumour tissue for subsequent treatment decisions can be challenging, often requiring invasive and potentially painful biopsies.
The ASPiRATION 2L trial will address this critical gap by evaluating the use of liquid biopsies, a simple blood test that can be repeated throughout a patient’s treatment. This approach, available through remote testing to every Australian with advanced oncogene-addicted NSCLC showing resistance to TKIs, offers a less invasive and more accessible method for monitoring tumour evolution and guiding treatment adjustments, ultimately enhancing patient care.
Moreover, ASPiRATION2L enables lung cancer to lead the genomics revolution in cancer care, with the potential to bring significant changes in survival and quality of life.
"Recognition of lung cancer in this way shines a much-needed spotlight on the challenges we face, and is a critical step forward in improving both research and patient outcomes. It also helps elevate lung cancer as a priority within the broader healthcare landscape, and I cannot wait to see this vision come to fruition! I am alive because of the research and advancements made in the field, and am privileged to still be here 10 years later, willing and able to work on this project."
A Vision for the Future
The Thoracic Group of Australasia is committed to advancing lung cancer research and improving patient outcomes. The ASPiRATION 2L trial represents a significant step forward in achieving this goal, positioning Australia as a global leader in precision medicine.
“Over the past decade, significant progress has been made in treating lung cancers, with highly effective therapies being selected at the time of diagnosis based on genomic testing of tumour tissue,” said Professor Ben Solomon.
“The ASPiRATION-2L trial presents a unique opportunity to redefine personalised medicine for lung cancer using liquid biopsy with ctDNA to guide treatment decisions, not just at the time of diagnosis, but throughout the patient journey.”
