Dynamic liquid molecular profiling in anaplastic lymphoma kinase (ALK) Non-Small Cell Lung Cancer

This study aims to use specialised blood tests to assess any changes in of the tumour DNA circulating in the blood of patients with advanced ALK-positive (ALK+) non-small cell lung cancer (NSCLC) throughout their diagnosis and treatment to help improve outcomes.

Who is it for?
You may be eligible for this study if you are an adult aged 18 years or older and you have been diagnosed with advanced ALK+ non-small cell lung cancer. Patients commencing but who have not started treatment with a new ALK-targeted tablet therapy may be eligible to participate in this study. This study is being conducted through the Australian Registry and Biobank of Thoracic Cancers (AURORA). Existing and new AURORA participants will be screened for eligibility and offered participation. Non-AURORA patients can be enrolled into AURORA through a referral by their treating clinician to an AURORA site specifically to participate in this study. Patients receiving treatment at a site not registered with AURORA will still receive their treatment at their local Center, whilst undergoing DYNAMALK activities through the AURORA site which may occur in person or virtually as appropriate.

Study details
All who choose to participate in this study will be asked to provide blood samples at three occasions over a 2 year period, once after they have enrolled, once at 6-12 weeks after enrolment and once again at 2 years after enrolment, or at any earlier time if they have evidence that their cancer has progressed and the current treatment is recommended to stop to consider a new approach.

Tissue samples will be collected where biopsies are performed as part of standard care. Collection of these samples will be organised to coincide with participants' scheduled appointments with their oncologist to minimise the need for additional travel requirements.

Participants who choose to enrol in this study will also be asked to allow the research team to review their previous medical history relevant to their NSCLC diagnosis and treatment. Results from the blood assessments will be provided to participants by their treating clinician within a few weeks after collection and may help their treating clinician to decide on the best treatment strategy.

It is hoped this research will identify how markers from DNA in the blood could be used to understand more confidently how well a treatment will work for patients with ALK+ NSCLC and identify markers that could be used to guide new therapies that will treat these cancers more precisely.

Description of the Control: No control group. This study has two parallel arms and outcomes will be reported separately for each arm. It is not designed to compare outcomes between arms. Outcomes within each group will be indirectly compared against published studies post-hoc.
Description of the Intervention: ctDNA profiling at three time points: (1) baseline, (2) +6-12 weeks coinciding with first on treatment imaging, (3) +24 months OR at disease progression whichever occurs first.

ctDNA profiling will involve provision of a single blood sample at each of the three time-points. Samples will be collected at the hospital of enrolment to be sent for centralised testing and reporting. Treating clinicians and patients will be provided real-time results from ctDNA profiling with decision to impact standard of care prescribing at the discretion of the treating clinician. Tissue samples will be obtained from standard care biopsies when available.

DYNAMALK is an AURORA sub-study with participation requiring enrolment in AURORA. Existing AURORA participants will be screened for DYNAMALK eligibility and offered participation. Non-AURORA patients can be enrolled into AURORA by their treating clinician specifically to participate in DYNAMALK.

DYNAMALK includes two arms based on standard of care treatment initiated by the treating clinician. Participants in ARM A will receive lorlatinib as first line treatment. Lorlatinib is being delivered as standard of care and access to lorlatinib is not reliant on participation in this profiling study. Participants in arm B will have received at least one prior ALK directed therapy as part of standard of care management. There is no requirement for duration or recency of prior ALK treatments. Prior treatment with chemotherapy or immunotherapy does not preclude participation.

Allocation to Intervention:

Description of the detailed clinicopathologic, baseline and temporal plasma ctDNA next-generation sequencing profiles
36 months months post-enrolment
Proportion of participants with changes in clinical management of ALK+ NSCLC based on their ctDNA profile results.

Changes in clinical management will be documented by the treating clinician and may include change in imaging or other monitoring schedule, or change in therapy.
36 months months post-enrolment

Consent to participate rate *uptake (%, patients enrolled in study/ patients offered study enrolment) *Local feasibility

Consent rate will be ascertained by audit of study enrolment/withdrawal logs to determine the number of participants enrolled vs. the number of participants approached for enrolment.
After last participant enrolment (estimated 16 months after study opened for enrolment)
Concordance of ALK plasma molecular results compared to ALK tissue molecular results by standard of care assays and non-standard comprehensive genomic profiling where available. Concordance will be assessed based on review of laboratory molecular profiling reports by study molecular tumour board.
36 months post-enrolment
Plasma ctDNA turn-around time to result in days (compared to standard of care molecular and tissue next generation sequencing if available) for an Asia Pacific population sequenced abroad. Turn around time is defined as date/time of sample collection to date/time of report availability, and will be collected from audit of pathology reports.
36 months post-enrolment
Identification of molecular sub-groups of interest determined by ctDNA profiling of blood samples. *Biomarker exploration
36 months post-enrolment

Side effect profiles varying according to chosen ALK-directed therapy, which is selected by the treating clinician as part of routine care

Arm A: advanced ALK+ patients, treatment naïve planned to start lorlatinib
Arm B: advanced ALK+ patients, pre-treated at resistance to any prior ALK directed line of treatment

DYNAMALK is an AURORA sub-study with participation requiring enrolment in AURORA. All existing AURORA participants will be screened for DYNAMALK eligibility and offered participation. Non-AURORA patients can be enrolled into AURORA by their treating clinician specifically to participate in DYNAMALK. 18 Years No limit Both males and females

Diagnosis other than ALK+ NSCLC

Hospital Peter MacCallum Cancer Centre 305 Grattan Street Melbourne Victoria 3000 Australia Australia

Commercial sector/Industry Pfizer Australia Commercial sector/Industry Guardant Health AMEA

N/A

Similar cost as usual care
Similar time commitment as usual care
Same amount of travel