Jun 04
2025
news
News Medical — SWOG S2302 Pragmatica-Lung study demonstrates value of streamlined clinical trials in real world settings
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.
Results will be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago on June 2nd by study co-chair Konstantin Dragnev, MD, of Dartmouth Cancer Center (Abstract LBA8671).
Pragmatica-Lung compared treatment with an immune checkpoint inhibitor-based combination of ramucirumab (Cyramza) and pembrolizumab (Keytruda) to physician’s choice of standard treatment in patients with stage 4 or recurrent non-small cell lung cancer (NSCLC) that had been previously treated with immunotherapy and chemotherapy. The study’s primary objective was to evaluate whether a survival benefit that had been seen with this regimen in the smaller, phase 2 S1800A trial (a Lung-MAP sub-study) would be validated in a larger, more representative population of patients.
Although the answer to the trial’s primary question is negative, the trial itself, in its speed, its broad and highly representative enrollment, and the reduced burden for clinic staff and participants alike, has been hugely positive in demonstrating the viability of a model for large, pragmatic clinical trials that are lean, inclusive, and quick, even with FDA registrational intent.”
Karen L. Reckamp, MD, MS, study chair of Cedars-Sinai Cancer
A planned second interim analysis of Pragmatica-Lung data in April found that it was unlikely the investigational combination would lengthen overall survival compared to standard of care. Based on the analysis, the trial’s Data and Safety Monitoring Committee (DSMC) recommended that results be publicly released.
The DSMC also reported that no safety concerns had been identified, and that patients clinically benefitting from treatment with the combination could continue the protocol treatment. Model letters summarizing the findings and the DSMC recommendations were sent to participating clinical sites for use in notifying clinicians and enrolled patients.
The April interim analysis found that, with 370 patient deaths reported, overall survival was not significantly different between the study arms, with a hazard ratio (HR; 95% CI) of 0.99 (0.81-1.22), with p = 0.46. Median overall survival was 10.1 months on the investigational arm and 9.3 months on the standard-of-care arm.
Pre-specified subset analyses evaluated treatment effects within squamous cell and non-squamous histologic subgroups. Among the 29 percent of enrolled patients who had squamous cell carcinoma, the HR (95% CI) was 0.82 (0.56-1.22), with p = 0.17. Among those with non-squamous histology, the HR (95% CI) was 1.09 (0.85-1.39), with p = 0.75. Longer-term follow-up data are needed to determine whether this difference represents a benefit for patients with squamous cell histology.
“For patients enrolled to Pragmatica-Lung, overall survival appears comparable across arms, so the investigational combination may offer patients a non-chemotherapy-based regimen that’s as effective as traditional chemo but that may be less toxic,” said the study’s lead biostatistician Mary W. Redman, PhD, of the SWOG Statistics and Data Management Center and the Fred Hutch Cancer Center.