Too targeted.

The Lung Matrix Trial is a UK multi-drug phase II umbrella trial of rationally-selected targeted therapy for advanced non-small cell lung cancer (NSCLC). Enrollment started with the integrated Stratified Medicine Programme 2 (SMP2) where tumor biopsies were collected and underwent next-generation sequencing looking for actionable mutations in 28 different genes. Patients with actionable mutations were allowed to enroll after failing (or refusing) standard of care therapy. Of the >5000 patients screened, 37% had mutations eligible for the trial. Only 14% of those (5% of screened) actually enrolled, with the most common reason for not enrolling being death on first-line therapy—a decent reason if you ask us. TBL: While the purpose of the study was to accelerate identification of promising targeted drug activity, the results thus far mostly highlight the challenges of running and establishing therapeutic effect in such a large scale precision medicine trial. | Middleton, Nature 2020