When less is more—reducing complexity in cancer trials

Oncology clinical trials submitted for regulatory review have become increasingly complex in their design and conduct. The Pragmatica-Lung Study (NCT05633602), sponsored by the US National Cancer Institute (NCI) and catalysed through an effort by the NCI and US Food and Drug Administration (FDA) to modernise clinical trials, represents a fundamental shift from this course, deploying a much simpler and more pragmatic design. The Pragmatica-Lung Study aims to confirm an initial signal for improved overall survival with pembrolizumab and ramucirumab versus investigator's choice of chemotherapy, observed in a small, randomised trial (Lung-MAP S1800A) in patients with advanced non-small-cell lung cancer who had progressed on or following front-line immunotherapy. 1 Reckamp KL Redman MW Dragnev KH et al. Phase II randomized study of ramucirumab and pembrolizumab versus standard of care in advanced non-small-cell lung cancer previously treated with immunotherapy-lung-MAP S1800A. J Clin Oncol. 2022; 40: 2295-2306 Crossref PubMed Scopus (63) Google Scholar The trial is uniquely designed to minimise barriers to enrolment and reduce trial complexity by broadening eligibility criteria and minimising data collection to focus on those outcomes that are most relevant to the primary objective—overall survival. The hope is that with a less complex trial design, the trial will be easier to open, more efficient to conduct, and more swift to answer the key clinical question: does combination therapy provide a survival advantage for patients versus the standard of care?