ENIGMA+: a national, decentralized, remote consent study for clinical data and biospecimen collection in patients with ALK-positive advanced NSCLC.

OBJECTIVE

Despite advances in ALK inhibitors for ALK fusion-positive (ALK+) non-small-cell lung cancer (NSCLC), drug resistance remains a challenge. Studies of treatment outcomes and resistance biomarkers are imperative for drug development, yet patient representation can be limited. This study evaluated the feasibility of a decentralized research infrastructure to establish a clinical and biospecimen repository, broadening patient access and inclusion.

PATIENTS AND METHODS

Patients with advanced ALK+ NSCLC across the United States were enrolled through remote informed consent. Clinical history and tumor molecular profiling data were collected at baseline and during remote follow-ups. Archival tumor and saliva biospecimens (for germline sampling) were obtained for analysis.

RESULTS

Of 87 eligible patients, 80 (92%) completed remote consent and enrolled. The clinical data collection rate was 100%, with archival tumor acquired from 80% and saliva samples from 65%. Patients represented 31 states, with 94% residing outside the study center's state and 90% receiving care elsewhere. Next-generation sequencing was conducted on 55 treatment-naïve and 18 treatment-resistant biopsies, all of whom received at least one prior second-generation ALK inhibitor, and 9 received lorlatinib. ALK resistance mutations were identified in 54% of treatment-resistant biopsies; other commonly co-altered genes included TP53 (18%) and CDKN2A/B (16%).

CONCLUSIONS

This study highlights the feasibility of a decentralized design to enhance the inclusion of a broader patient population with ALK+ NSCLC. This establishes a scalable framework that may help overcome barriers to patient participation in research, with the goal of improving therapy development and patient outcomes. The Elucidating Novel Immune and Genomic Markers for ALK+ study accrual and analysis continue (NCT04881916).