DYNAMALK, a TOGA-endorsed study led by A/Prof Malinda Itchins, is an innovative study that focuses on patients who have recently started or switched to lorlatinib therapy. Lorlatinib is a targeted drug designed to combat ALK+ non-small cell lung cancer (NSCLC), a specific type of lung cancer. Through the TOGA Research Development Pathway, DYNAMALK was reviewed by the Advanced NSCLC Working Group and TOGA Scientific Committee, refined through multidisciplinary and consumer input, and developed into a national study.
The DYNAMALK clinical trial has now officially closed to recruitment, with preliminary results presented by study lead A/Prof Malinda Itchins at the 2025 World Conference on Lung Cancer (WCLC). This landmark Australian lung cancer study investigates how liquid biopsy and circulating tumour DNA (ctDNA) can guide precision treatment decisions for people living with ALK-positive NSCLC.
Understanding the Trial’s Objectives
As explained by A/Prof Malinda Itchins, “when someone has a type of lung cancer that is ALK-positive, they often take inhibitor drugs directed to the ALK target to help treat it. But over time, the cancer can become resistant to this medicine. Right now, doctors don’t have a reliable way to predict when this might happen or how to adjust treatment based on each person’s specific situation.”
DYNAMALK aims to address this critical challenge. By analysing comprehensive genomic profiles, including those derived from circulating tumor DNA (ctDNA) – a “liquid biopsy” obtained from blood samples – researchers hope to:
- Predict resistance: Identify early signs of treatment resistance, allowing for timely adjustments to therapy.
- Guide treatment decisions: Personalise treatment plans based on individual genetic profiles.
- Improve outcomes: Ultimately, enhance the lives of patients with ALK+ NSCLC by improving treatment effectiveness and potentially extending survival.
Study Design and Structure
Participants were eligible from anywhere in Australia, with ctDNA kits express-shipped to ensure equal access.
Arm A: First-line lorlatinib treatment
Arm B: Subsequent-line treatment of clinician choice (requiring a planned systemic therapy change)
ctDNA samples were collected at baseline, at 2–3 months on treatment, and again at 24 months or progression.
The study was conducted through AURORA, a national real-world data platform, which operated across 21 active hospital sites nationwide. Innovative telehealth-based consent and participation processes ensured access for patients in regional and remote Australia.
Preliminary Results and Impact
The DYNAMALK trial opened in August 2023 and completed enrolment in July 2025, successfully recruiting 61 patients over 20 months. Follow-up will continue until July 2028.
At the data cut-off (15 August 2025), the median time on treatment was 8.5 months (Arm A) and 9.5 months (Arm B).
Early findings indicate that ctDNA testing effectively captures the dynamic genomic landscape of ALK+ NSCLC—from initial diagnosis through to the development of resistance—complementing tissue-based testing. The average turnaround time for ctDNA sample processing was just 12 days, demonstrating its potential for near real-time clinical application.
These early insights from DYNAMALK are shaping the next phase of research, informing the design of TOGA’s upcoming ASPI-2L study, which will extend serial ctDNA monitoring to all oncogene-driven NSCLC.
Additionally, A/Prof Malinda Itchins was awarded a 2026 TOGA Inspirational Research Grant to examine if interpreting PET imaging together with ctDNA results, provides a greater insght into developing resistance.
Consumer Co-Design and Collaboration
A hallmark of DYNAMALK is its strong consumer partnership. Initially planned for newly diagnosed metastatic ALK+ NSCLC patients commencing lorlatinib, the study was expanded to include patients switching to lorlatinib in later lines of therapy following consumer feedback. When funding for this expansion was unavailable, consumer representatives successfully raised over $100,000—broadening both the research question and the diversity of participants. Hear A/Prof Malinda Itchins describe how consumer engagement changed the DYNAMALK study design.
Natalie Dubs, a lung cancer survivor celebrating ten years of life, shared her inspiring story:
“Ten years ago, I was diagnosed with Stage 4 ALK+ lung cancer. Today, I’m celebrating a decade of living life to the fullest, thanks to incredible advancements in medical research, my husband’s and family support and my oncologist forefront knowledge in lung cancer treatments. I’ve travelled the world, bought and renovated a home, and even welcomed a furry friend named Taicho into my life. While managing the disease, I haven’t let it stop me from pursuing my dreams and continuing working.”
Natalie’s commitment to raising over $16,000 for DYNAMALK exemplifies the incredible spirit of the lung cancer community.
DYNAMALK highlights how precision oncology, real-world data, and consumer co-design can work together to transform lung cancer research in Australia. The study’s success underscores the importance of national collaboration, equitable access, and patient-centred innovation in delivering next-generation cancer care.
Acknowledgments
The DYNAMALK research project is grateful for the generous support of Lung Foundation Australia and Rare Cancers Australia. Their contributions are vital in advancing this crucial research and improving the lives of patients with ALK+ lung cancer.
