Study of Plasma NGS for Assessment, Characterization, Evaluation of Patients With ALK Resistance

SPACEWALK is an innovative remote consent and participation study using next-generation sequencing (NGS) of plasma cell-free DNA (cfDNA) to characterize resistance mechanisms arising in ALK-positive non-small cell lung cancer (NSCLC) after progression while on a next generation ALK tyrosine kinase inhibitor (TKI). Additionally, the study will capture the potential of genomic-driven resistance therapy approach for effecting outcomes in patients with advanced ALK-positive NSCLC and TKI resistance. Finally, the study will assess the role of repeat plasma NGS in evaluating drug response. The study will accrue patients with advanced ALK-positive NSCLC on systemic progression (outside the brain) while on treatment with a next-generation ALK TKI. Any patient interested in the study will find information about the study on the study website. The patient will consent remotely through the study website and documentation of advanced ALK-positive NSCLC and systemic progression while on a next-generation ALK TKI. The study team will reach out to the patient to confirm eligibility and send a blood collection kit. In the study kit the study participants will find all the necessary materials for local blood draws, and collected specimens will be sent directly to the central study laboratory (Resolution Bioscience) for plasma NGS. Plasma NGS of cfDNA will involve sequencing of 19 genes, including ALK, permitting remote tumor genotyping. Plasma NGS analysis and results will be done following standard procedures of the Resolution Bioscience CLIA-certified laboratory. Results will be sent to study participants, their physicians and study team within 1-2 weeks. Plasma NGS reports will not include any specific treatment recommendations but will describe the presence of an ALK rearrangement, ALK resistance mutation, or other relevant mutations. Study participants are followed remotely. The study coordinator will contact the participants weekly for 4 weeks after enrolled into the study to learn of any new treatment initiation and to release an additional plasma collection kit 2-4 weeks after starting treatment. Study participants will then be remotely contacted every 3 months to follow clinical outcomes on therapy for up to 2 years. If the cancer progresses on the participant's new treatment, the patient will have the option to provide a third blood specimen. Medical records and local imaging will be collected and studied. The primary objective of the study is to characterize ALK TKI resistance to next-generation ALK TKIs in patients with advanced ALK-positive NSCLC. Secondarily, the investigators will assess the potential of plasma NGS to impact outcome on treatment by studying time to treatment discontinuation. Serial plasma NGS will also be assessed as a response biomarker. A total of 300 patients are planned to be enrolled, with the expectation that approximately 200 will have tumor-related mutations detected in plasma NGS.