ENIGMA+: A National, Decentralized, Remote Consent Study for Clinical Data and Biospecimen Collection in Patients with ALK-Positive Advanced NSCLC.

Abstract

Background: 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 U.S. 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. 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 nine 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 ENIGMA+ study accrual and analysis continue (NCT04881916).