Dr Reckamp on the Future Implications of the PRAGMATICA-LUNG Trial in Lung Cancer

“The pragmatic design is something that could be followed. Especially in the second-line setting or subsequent-line settings, where there are many combinations that [we] want to [test], and we’ve had many negative results, these are ways to get trials done more efficiently, include a more generalizable population, and get the answers in an efficient way.”

Karen L. Reckamp, MD, director of Medical Oncology, associate director of Clinical Research, and the medical oncology director of the Lung Institute at the Samuel Oschin Cancer Center at Cedars Sinai, discussed how the feasibility of the phase 3 PRAGMATICA-LUNG trial (NCT05633602) design may influence the uptake of future pragmatic clinical trials for patients with lung cancer.

The PRAGMATICA-LUNG trial results were reported in June 2025. This was a randomized, FDA registration–directed study evaluating ramucirumab (Cyramza) in combination with pembrolizumab (Keytruda) vs investigator’s choice of standard-of-care (SOC) therapy in patients with advanced non–small cell lung cancer. What distinguishes this trial is its pragmatic design, which allowed for a broad and inclusive eligibility criteria, according to Reckamp. The only limitations imposed were on the number of prior lines of therapy and the patients’ ability to receive treatment consistent with accepted standards of care (SOCs).

Importantly, patients in the SOC arm received any treatment the investigator deemed appropriate, resulting in a highly heterogeneous and real-world-representative comparator group, Reckamp reported. This inclusive approach enabled the enrollment of a demographically diverse cohort; for instance, 13% of patients identified as Black.

Although the study did not demonstrate a statistically significant improvement in overall survival (OS) between the ramucirumab/pembrolizumab combination and SOC therapies, the investigational combination was associated with fewer treatment-related toxicities, Reckamp said. Notably, the trial successfully enrolled 838 patients in 21 months, a rare achievement within the National Clinical Trials Network for a lung cancer study, Reckamp emphasized. This rapid accrual reflects the advantages of the pragmatic design, which could serve as a model for future clinical trials, particularly in the second-line or later-line settings, where multiple therapeutic options exist and traditional trial models have frequently yielded negative results, Reckamp explained.