News

ASPiRATION 2L: Liquid Biopsy Clinical Trial for Advanced Lung Cancer Patients Across Australia

The Australia-wide trial using liquid biopsy to guide treatment after targeted therapy progression in advanced lung cancer and how you can participate. 

The ASPiRATION-2 Liquid (ASPi-2L) program is a landmark national initiative aiming to change how lung cancer is diagnosed, monitored, and treated across Australia. Led by Prof Ben Solomon, Prof Nick Pavlakis, and TOGA, this innovative study builds on the success of the original ASPiRATION trial, which delivered nationwide access to comprehensive tumour-based genomic testing for people with advanced lung cancer. The ASPi-2L program, supported through a successful $14.7 MRFF Frontier Health and Medical Research Grant, will establish a national framework for delivering liquid biopsy testing, focused on providing access to people with metastatic non-small cell lung cancer (mNSCLC) after their cancer progresses on targeted therapy. Through the delivery of non-invasive liquid biopsy testing, the clinical study aims to help shape treatment decisions and enable personalised treatment based on the tumour’s changing molecular profile. 

Click here for remote referral information and links, or contact the ASPi-2L study team at info.aspiration2@sydney.edu.au or call 02 9351 2409 for more information.

Why is ASPiRATION 2L important for oncogene-driven lung cancer? 

In oncogene-driven mNSCLC, first-line targeted therapies such as tyrosine kinase inhibitors (TKIs) can control cancer for many months or even years. However, the cancer may eventually progress despite treatment and when this happens, it often leaves patients and clinicians with limited targeted treatments options. 

When that happens, doctors may need to review the treatment plan and this often requires resampling of the tumour. Currently, this involves a tissue biopsy that is invasive, requires hospitalisation, and is sometimes risky or not possible at all due to the location of the tumour or the particular patient circumstances. ASPiRATION 2L uses liquid biopsy testing to better understand the tumour’s molecular changes. This opens the door for patients to require a simple blood test (known as a ‘liquid biopsy’) to help identify the most appropriate next treatment. 

What is a liquid biopsy in lung cancer?

A liquid biopsy is a blood test that detects fragments of tumour DNA called circulating tumour DNA (ctDNA) that are released into the bloodstream. 

Compared to a traditional tissue biopsy, it is: 

  • Less invasive – no surgery or lung needle biopsy required
  • Repeatable over time – can track tumour changes during treatment
  • Fast – results can return sooner, allowing quicker treatment decisions

For people with lung cancer, liquid biopsy is particularly useful for detecting new mutations that emerge during treatment, potentially opening up targeted therapy or clinical trial options.  

To learn more listen to the TOGA podcast about liquid biopsy with three leaders in the lung cancer field. 

How ASPi-2L will achieve liquid biopsy informed precision oncology 

Over the next five years, ASPiRATION-2 Liquid will: 

  • Recruit 500 Australians with metastatic non-small cell lung cancer (NSCLC) harbouring any actionable mutations whose cancer has progressed after targeted therapy. 
  • Use liquid biopsy to guide treatment decisions throughout a patient’s journey, not just at diagnosis. So even if a patient progresses after the initial liquid biopsy and tailored treatment through ASPi-2L, the opportunity will be available to repeat the liquid biopsy and personalisation of further lines of treatment. 
  • Connect patients to the most suitable therapies, whether through PBS-funded treatments, clinical trials, or other programs. 
  • Test the real-world benefits and cost-effectiveness of integrating liquid biopsy into standard care. 
  • Ensure equal access nationwide through telehealth, remote consent, and virtual molecular tumour boards. 
 
A flowchart detailing the ASPiRATION 2-Liquid study design. The study is an observational cohort of 500 adults with metastatic NSCLC, who have disease progression on targeted therapy and an ECOG performance status of 0-2. After consenting to screening, participants undergo both liquid biopsy and, if a biopsy was performed, tissue NGS. The liquid biopsy uses either ctTSO500 or FoundationOne Liquid CDx, while the tissue NGS uses TSO500 or FoundationOne CDx. The results from these tests are categorized into three possible outcomes: 1) No new actionable alteration found (estimated 30% of cases), leading to a "Standard of care" pathway with non-targeted therapies like immunotherapy or chemotherapy. 2) Liquid biopsy is uninformative (estimated 30% of cases), leading to a PBS pathway with targeted therapy. 3) A new actionable alteration is identified (estimated 40% of cases). The results are then presented to a Molecular Tumour Board for a guided treatment recommendation, which can lead to four different pathways: a PBS pathway with targeted therapy, an Access program with targeted therapy, an Industry trial with targeted therapy, or a TOGA trial with targeted therapy.
Schematic of the proposed ASPiRATION-2L study incorporating liquid biopsy, molecular tumour board treatment recommendation and options to access further treatments.

How do ASPiRATION 2L results guide treatment? 

Test results are reviewed by a Molecular Tumour Board (MTB) — a multidisciplinary panel of lung cancer experts. The MTB report to the referring clinician includes: 

  • Detected mutations or molecular changes
  • Potential targeted therapy or standard care options
  • Relevant clinical trials or drug access schemes

This liquid biopsy and MTB cycle is repeated at key stages of treatment, ensuring recommendations remain aligned with the cancer’s evolution. 

 

Who can join the ASPiRATION 2L trial? 

Any adult in Australia with oncogene-driven mNSCLC whose disease has progressed after first-line TKI therapy can be referred. 

Participation pathways include: 

  1. Activated trial site – patient’s hospital is a participating site 
  1. Remote referral and consent – coordinated by the Sydney Clinical Trials Centre 

Once enrolled, the referring site collects a blood sample for next-generation sequencing (NGS), which is analysed in a central laboratory. 

Clinical trial schema: patients tested with liquid biopsy at baseline, start second-line treatment, and undergo repeat testing with liquid biopsy at each progression
Schema of a clinical trial patient pathway showing molecular testing and access to liquid biopsy in ASPI-2L. At baseline, patients undergo testing and may receive liquid biopsy before starting prescribed second-line treatment. At first progression, patients undergo repeat testing including liquid biopsy, with subsequent cycles of treatment and testing continuing.

Following the Molecular Tumour Board recommendation 

Following the report, the clinician and patient may choose to: 

  • Continue the current standard of care
  • Switch to another PBS-reimbursed therapy
  • Enrol in a clinical trial (TOGA-led or industry-sponsored)
  • Access treatment via a drug access program

All treatment options follow the usual regulatory and consent requirements. 

Referring patients to the ASPiRATION-2L study

We want clinicians and cancer centres across Australia to be part of this national effort. There are two pathways to referring participants to the study:  

1. Remote referral

Any medical oncologist in Australia outside of a participating site can refer a patient to the ASPi-2L study.  

Eligibility is to be confirmed by the referring clinician and registration will be performed by the NHMRC CTC as soon as possible after informed consent has been obtained. 

Click here for remote referral information and links, or contact the ASPi-2L study team at info.aspiration2@sydney.edu.au or call 02 9351 2409 for more information.

2. Enrolment at one of the participating sites

If you wish to refer a patient to one of the participating sites, please contact the relevant Principal Investigator or aspiration2.study@sydney.edu.au

Site
Principal Investigator
ACT
Canberra Hospital
Geoffrey Peters
NSW
Royal North Shore Hospital
Nick Pavlakis
Chris O’Brien Lifehouse
Malinda Itchins
Liverpool Hospital
Victoria Bray
St George Hospital
Chee Lee
Nepean Hospital
Pei Ding
QLD
Princess Alexandra Hospital
Ken O’Byrne
The Prince Charles Hospital
Brett Hughes
Sunshine Coast University Hospital
Bryan Chan
SA
Queen Elizabeth Hospital
Rachel Roberts-Thomson
TAS
Royal Hobart Hospital
Rebecca Tay
VIC
Peter MacCallum Cancer Centre
Ben Solomon
St Vincent’s Hospital Melbourne
Melissa Moore
Austin Hospital
Sagun Parakh
Monash Medical Centre – Clayton
Surein Arulananda
WA
Sir Charles Gairdner Hospital
Samantha Bowyer
Fiona Stanley Hospital
Lydia Warburton

How can I be more involved with ASPI 2L?  

If you are interested in conducting a clinical trial or are involved in an ongoing clinical trial that would benefit from recruitment via ASPi-2L please submit the study concept or protocol to info@thoraciconcology.org.au.
TOGA’s concept process and further information can be found here.

Studies proposing to recruit through ASPi-2L will be reviewed by the ASPi-2L executive committee and if approved, will be mentioned on the MTB report when a relevant patient is identified. This opportunity is available to TOGA members, non-members and industry. The clinical trial needs to be independently funded. There may be some required sharing of data to enable follow up of patients on the main cohort study. 

Learn more about TOGA clinical trials and how innovative studies are improving outcomes for people with lung cancer.

Share this

Facebook
Twitter
LinkedIn
The DEFIANT trial will evaluate datopotamab deruxtecan (Dato-DXd) in EGFR exon 20 insertion NSCLC after targeted therapy and chemotherapy.
Discover the major advances from TOGA ASM 2026, including lung cancer screening, precision medicine, immunotherapy, survivorship and multidisciplinary care shaping the future of thoracic oncology.
Professor Robert Stirling OAM devoted his career to improving the lives of people with lung cancer through clinical excellence, research, education and compassionate leadership.
Their work is often invisible, but its impact isn't. Specialist Lung Cancer Nurses are quietly becoming the backbone of modern lung cancer care.
Teletrials, also known as digi trials, are when a clinician at a primary site uses telehealth (videoconference or telephone calls) to enrol, consent, treat and/or
A simple guide to what happens after a lung CT scan in the Australian National Lung Cancer Screening Program
Updates from our Inspirational Research Grant 2025 recipients on pioneering lung microbiome research and its impact on immunotherapy efficacy.
Clinicians, nurses, consumers and health service leaders came together at TOGA’s Lung Cancer Optimal Care Pathway workshop to examine why Australia continues to struggle to
Understanding the language helps patients, families and clinicians stay informed, confident and part of the conversation.
TOGA is pleased to announce the latest appoints for our Scientific Committee.
Discover how a vibrant Lunar New Year Banquet, organised by Dr. Angeline Low and Ms. Maria Chan, raised over $50,000 for vital lung cancer research.
The MRFF is holding $1B+ in unspent funds. Learn why TOGA is calling for the release of this research funding to accelerate lung cancer breakthroughs
Discover TOGA’s FY25 highlights, including the new Strategic Plan, clinical trial milestones and record membership growth across Australia and New Zealand.
The Preventative and Quality Care Working Group represents TOGA’s commitment to improving the outcomes of thoracic cancers.
TOGA’s Working Groups are evolving to better reflect where thoracic cancer research is heading: From prevention and early detection through to advanced disease and living
Learn how to turn your endorsed research concept into a clinical trial; from sponsor selection to budgeting, data, safety and protocol design.
Learn how to design an investigator-initiated clinical trial, from refining your research idea to securing TOGA endorsement and funding.
Learn why EGFR-positive lung cancer disproportionately affects Asian populations and non-smokers. Discover modern targeted therapies and symptoms to watch for.
Discover how 2025 transformed lung cancer care in Australia. Explore the impact of national screening, modern diagnostics, and new PBS treatment approvals.
Let's take a moment to celebrate the incredible guests, ground breaking discussions, and dedicated listeners that made 2025 our most successful year yet.
If you are interested in joining TOGA on a Committee, please submit your nominations by 30 January 2026
The final Scientific Meeting of 2025 was held in November. Five concepts were presented, spanning both Recurrent and Metastatic NSCLC populations and four Mesothelioma concepts.
Bispecific antibodies target two pathways at once, reshaping lung cancer treatment through dual checkpoint blockade and targeted precision.
Research advances only improve outcomes when they are accessible to patients. TOGA drives change in lung cancer care by advocating through stakeholder submissions, including PBS.......
We are excited about awarding new grants but first, we check in on progress made by our 2024 recipients....
Learn how TOGA’s ASPiRATION study led to Medicare-funded genomic testing for lung cancer and national best practice guidelines in Australia.
Optimise cancer care for older Adults with practical tips and tools to implement person-centred geriatric oncology.
DYNAMALK is a significant clinical trial investigating the potential of comprehensive genomic profiling to revolutionise the treatment of ALK+ Non-Small Cell Lung Cancer (NSCLC)
Liquid biopsy is revolutionising lung cancer care by using a blood test to examine the tumour without the need for a lung biopsy.
OCEANiC will determine if patients with resected stage II to IIIA EGFR mutant NSCLC require intensification of osimertinib monotherapy with chemotherapy.
Latest results from the SHERLOCK clinical trial show promising first-line outcomes for patients with KRAS G12C-mutated lung cancer, combining sotorasib with chemotherapy and bevacizumab.
A re-cap of the Scientific Committee meeting in August 2025 and the year to date.
Celebrating TOGA's leadership transition: We honour the service of our past Board members and welcome the new Chair and Directors who will chart TOGA’s future.
Why doesn’t immunotherapy work for all lung cancer patients? This article breaks down T-cell resistance mechanisms and what clinical trials are doing to overcome them.
Precision medicine has revolutionised lung cancer treatment by matching therapies to a patient’s genetic profile. Learn more.....
An in-depth recap of the 2025 Annual Scientific Meeting. Read about the key takeaways, a new strategic plan, and who took home the top awards.