The SWOG S2302 Pragmatica-Lung trial, which broke new ground with its streamlined pragmatic design, unusually broad eligibility criteria, and reduced data collection, has quickly answered its primary question, finding that the investigational combination it tested did not significantly extend overall survival compared to standard of care treatments. Importantly, the phase 3 trial’s rapid development and implementation, coupled with its successful enrollment of a group of patients broadly representative of the larger U.S. population, establish Pragmatica-Lung as a paradigm-shifting model for the design and conduct of future large randomized studies.