The phase 3 S2302 Pragmatica-Lung study offers a new blueprint for cancer clinical trials, one that emphasizes simplification, inclusivity, and real-world applicability, according to Konstantin Dragnev, MD, of Dartmouth Cancer Center. By minimizing protocol requirements and simplifying enrollment, the study reduces complex barriers that have historically limited clinical trial participation. This approach may help broaden the reach of investigational therapies to patient populations often excluded from clinical research, he said.
S2302 Pragmatica-Lung is a randomized, registration-intent trial comparing pembrolizumab plus ramucirumab with standard of care in patients with advanced non–small cell lung cancer (NSCLC) who have previously received both platinum-based chemotherapy and immunotherapy.
According to Dragnev, the true innovation of the trial lies in its pragmatic design. In contrast to an explanatory trial that tests efficacy under ideal conditions, a pragmatic trial asks, “Does this intervention work under usual conditions?” he explained.
At the Summit on Cancer Health Disparities 2025 in Seattle, Dragnev discussed the trial, which was then formally presented a few weeks later at the 2025 ASCO Annual Meeting in June, as a potential model for future studies. “This trial addresses a major unmet need in the lung cancer community,” he said, referring to acquired resistance to immunotherapy. “As immunotherapy becomes more common across all stages of lung cancer, designing treatments to overcome resistance is increasingly critical.”
A Study With Real-World Reach
The trial’s predecessor, the phase 2 S1800A study, demonstrated a survival benefit for the pembrolizumab plus ramucirumab combination; median overall survival was 14.5 months versus 11.6 months with standard therapy. “As exciting as those results were, they needed to be validated,” said Dragnev. “And that’s what led to the design of Pragmatica-Lung.”
The study capitalized on a known drug combination with a well-characterized safety profile. This allowed researchers to focus on reducing the burden of clinical trial participation, particularly in underrepresented populations. The design incorporated:
- Limited eligibility criteria
- No required labs or imaging
- Heavy reliance on investigator discretion
- A simplified study calendar and data collection structure
The study’s primary objective was overall survival, with a secondary objective of summarizing serious and unexpected high-grade (grade ≥3) treatment-related adverse events. “‘Unexpected’ was the key word here,” he said.
“Patients were treated as they would be in real-world practice,” he added. “And investigators were empowered to make decisions consistent with their usual care models.”
Supporting Inclusion Through Simplicity
From the beginning, the study team focused on rapid, representative accrual. With support from organizations including the Friends of Cancer Research and the Foundation for the National Institutes of Health, the trial launched in March 2023 and accrued more than 700 patients across more than 2500 sites in the United States—both academic and community-based—by December 2024.
Dragnev emphasized the “convergence of many factors” that made the trial possible, including growing awareness of trial inequities, post-COVID staffing limitations, and leadership from the National Cancer Institute and FDA encouraging pragmatic trial designs.
Importantly, the study included a recruitment and retention plan shaped by patient advocates and community leaders. Plain-language summaries, culturally appropriate outreach materials, and a social media tool kit were used to reach sites serving patients from historically underrepresented backgrounds—particularly across the southeastern states.
This study highlights the importance of removing participation barriers to promote more inclusive clinical research. “Patients want to enroll in trials,” Dragnev noted. “But standard designs often create barriers that prevent them from doing so.”
By eliminating unnecessary procedures, relaxing eligibility requirements, and streamlining data collection, pragmatic trials make participation more feasible for a wider range of patients.
Although the study results are still pending, data from Pragmatica-Lung may offer more than clinical insight, according to Dragnev. It offers a model for how to design trials that are accessible, equitable, and scalable.
“The pragmatic design approach for registrational intent trials is novel and potentially paradigm-changing,” he said. “And more importantly, it promotes the inclusion of all participants with the disease.”
Source
Dragnev K, Redman R, Reckamp, et al. PRAGMATICA-LUNG (SWOG S2302): A prospective, randomized study of ramucirumab plus pembrolizumab versus standard of care for participants previously treated with immunotherapy for stage IV or recurrent non-small cell lung cancer. J Clin Oncol. 43, 2025; suppl 17; abstr LBA8671.