ALCHEMIST (Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials)

ALCHEMIST opened in 2014 as three linked NCI trials. The screening protocol A151216 collects tumour and blood from patients with completely resected stage IB to IIIA non-squamous (later also squamous) non-small-cell lung cancer, tests centrally for EGFR mutations and ALK rearrangements, and follows everyone for recurrence with periodic re-sequencing. Patients with an EGFR mutation were offered A081105, erlotinib for two years against placebo after standard adjuvant chemotherapy; those with an ALK rearrangement were offered E4512, crizotinib against observation; and from 2016 those with neither were offered ANVIL (EA5142), a year of nivolumab against observation. A later chemo-immunotherapy trial, ACCIO, joined the family.

The platform has recruited several thousand patients and its treatment trials have all completed or closed to accrual. The strategic question it was built to answer, whether a targeted adjuvant drug prevents relapse in EGFR- and ALK-driven early lung cancer, was answered first by industry trials with newer drugs: ADAURA showed osimertinib prolongs disease-free and overall survival after EGFR-mutant resection and won approval in 2020, and ALINA did the same for alectinib in ALK-positive disease with approval in 2024. Both changed the standard of care while ALCHEMIST was still following its patients, so its erlotinib and crizotinib comparisons are now read as evidence about older drugs and about the natural history of resected driver-positive disease.

What ALCHEMIST has already delivered is the largest prospectively sequenced cohort of resected lung cancer with long follow-up, a template for adjuvant umbrella trials, and the demonstration that routine molecular testing after surgery is feasible across community sites in the United States. Its remaining value lies in its biobank, in the ANVIL immunotherapy comparison and in the recurrence samples that show how driver-positive cancers evolve after surgery.