Lung cancer trial reports model for faster, leaner, more representative trials

The SWOG S2302 Pragmatica-Lung trial, which broke new floor with its streamlined pragmatic design, unusually broad eligibility standards, and lowered information assortment, has rapidly answered its major query, discovering that the investigational mixture it examined didn’t considerably prolong general survival in comparison with normal of care remedies.

Importantly, the section 3 trial’s speedy improvement and implementation, coupled with its profitable enrollment of a bunch of sufferers broadly consultant of the bigger U.S. inhabitants, set up Pragmatica-Lung as a paradigm-shifting mannequin for the design and conduct of future massive randomized research.

Outcomes can be offered on the 2025 American Society of Medical Oncology (ASCO) Annual Assembly in Chicago on June 2 by examine co-chair Konstantin Dragnev, MD, of Dartmouth Most cancers Middle (Summary LBA8671).

Pragmatica-Lung in contrast remedy with an immune checkpoint inhibitor-based mixture of ramucirumab (Cyramza) and pembrolizumab (Keytruda) to doctor’s alternative of ordinary remedy in sufferers with stage 4 or recurrent non-small cell lung most cancers (NSCLC) that had been beforehand handled with immunotherapy and chemotherapy.

The examine’s major goal was to judge whether or not a survival profit that had been seen with this routine within the smaller, section 2 S1800A trial (a Lung-MAP sub-study) can be validated in a bigger, extra consultant inhabitants of sufferers.

“Though the reply to the trial’s major query is detrimental, the trial itself, in its velocity, its broad and extremely consultant enrollment, and the lowered burden for clinic workers and members alike, has been vastly constructive in demonstrating the viability of a mannequin for giant, pragmatic medical trials which can be lean, inclusive, and fast, even with FDA registrational intent,” mentioned examine chair Karen L. Reckamp, MD, MS, of Cedars-Sinai Most cancers.

A deliberate second interim evaluation of Pragmatica-Lung information in April discovered that it was unlikely the investigational mixture would lengthen general survival in comparison with normal of care. Based mostly on the evaluation, the trial’s Information and Security Monitoring Committee (DSMC) beneficial that outcomes be publicly launched.

The DSMC additionally reported that no security issues had been recognized, and that sufferers clinically benefitting from remedy with the mixture may proceed the protocol remedy. Mannequin letters summarizing the findings and the DSMC suggestions have been despatched to taking part medical websites to be used in notifying clinicians and enrolled sufferers.

The April interim evaluation discovered that, with 370 affected person deaths reported, general survival was not considerably completely different between the examine arms, with a hazard ratio (HR; 95% CI) of 0.99 (0.81-1.22), with p = 0.46. Median general survival was 10.1 months on the investigational arm and 9.3 months on the standard-of-care arm.

Pre-specified subset analyses evaluated remedy results inside squamous cell and non-squamous histologic subgroups. Among the many 29% of enrolled sufferers who had squamous cell carcinoma, the HR (95% CI) was 0.82 (0.56-1.22), with p = 0.17. Amongst these with non-squamous histology, the HR (95% CI) was 1.09 (0.85–1.39), with p = 0.75. Longer-term follow-up information are wanted to find out whether or not this distinction represents a profit for sufferers with squamous cell histology.

“For sufferers enrolled to Pragmatica-Lung, general survival seems comparable throughout arms, so the investigational mixture could supply sufferers a non-chemotherapy-based routine that is as efficient as conventional chemo however that could be much less poisonous,” mentioned the examine’s lead biostatistician Mary W. Redman, Ph.D., of the SWOG Statistics and Information Administration Middle and the Fred Hutch Most cancers Middle.

The S2302 Pragmatica-Lung trial is led by the SWOG Most cancers Analysis Community, supported by the Nationwide Most cancers Institute (NCI), a part of the Nationwide Institutes of Well being (NIH), and carried out inside the NCI’s Nationwide Medical Trials Community (NCTN).

The examine was meant to function a prototype for giant pragmatic trials that would cut back the burden of participation for each medical websites and sufferers, would promote enrollment of all sufferers with the illness, and might be developed and carried out extra effectively, giving us earlier solutions.

It was developed in session with the U.S. Meals and Drug Administration’s (FDA’s) Oncology Middle of Excellence and with collaborative enter from the NCI’s Division of Most cancers Therapy and Prognosis, the advocacy group Pals of Most cancers Analysis, and the NCTN’s Alliance for Medical Trials in Oncology.

To make the trial accessible to the widest doable vary of sufferers, at as many remedy websites as doable, Pragmatica-Lung was designed with comparatively few restrictions on which sufferers with superior NSCLC can be eligible to enroll. The group that in the end did enroll appears very like the U.S. inhabitants general, with sturdy illustration of a number of demographic teams which can be usually understudied in medical trials.

Of the 838 enrolled sufferers, 22% have been non-white, 13% have been Black, and 15% lived in rural places. This broad illustration helps make sure the trial’s outcomes are generalizable throughout the U.S. inhabitants. (See ASCO Summary 11016 for extra particulars on growing illustration on this trial.)

With its swift enrollment and lowered burden of knowledge assortment, the trial was capable of reply its major query in simply over two years, way more rapidly than the everyday section 3 examine. It opened in March 2023, accomplished enrollment by December 2024, and notified taking part websites of preliminary ends in April 2025.

The trial’s design stage was additionally unusually temporary—examine protocol improvement, from evaluate of the preliminary idea to check activation, was accomplished in simply 200 days, chopping about 100 days off of what would sometimes be thought-about an environment friendly timeline for constructing a section 3 examine of this kind. Of observe is that this speedy timeline was achieved in a examine with registrational intent—designed in order that outcomes might be used, if wanted, in an software for FDA evaluate of the remedy.

“Designing trials so that they take a look at new remedies in settings that replicate on a regular basis, real-world follow removes limitations to participation and speeds trial enrollment and completion. Pragmatica-Lung gives a paradigm-shifting instance in trial conduct that ought to be utilized to future massive randomized research, together with research with FDA registrational intent,” mentioned Jhanelle E. Grey, MD, of Moffitt Most cancers Middle, and chair of the SWOG lung committee.

Supplied by
SWOG Most cancers Analysis Community