The National Cancer Institute (NCI) announced that it has helped launch the randomized phase III Pragmatica-Lung trial examining the efficacy of ramucirumab plus pembrolizumab in treating patients with advanced non–small cell lung cancer (NSCLC). The new study is one of the first NCI-supported clinical trials to use a trial design that removes many of the barriers preventing patients from joining clinical trials and aims to promote a pragmatic approach to increase clinical trial accessibility.
Background and Previous Lung-MAP Substudy
The Pragmatica-Lung trial (ClinicalTrials.gov identifier NCT05633602) is part of a broader effort by the National Institutes of Health and the U.S. Food and Drug Administration (FDA) to modernize clinical trials. Pragmatic clinical trials may have fewer and simpler eligibility criteria than conventional trials, while still ensuring patient safety. The hope is that this type of simplified trial can be less burdensome to patients and researchers, be more representative of the real-world patient population, accrue study participants faster, and serve as a model for future cancer clinical trials.
“These trials will make it easier for physicians who do not work in big academic medical centers to enroll their patients, resulting in participation by more diverse populations,” noted James H. Doroshow, MD, Director of the Division of Cancer Treatment and Diagnosis and Deputy Director of Clinical and Translational Research at the NCI. “Making trials more accessible, while upholding rigorous scientific and safety standards, means that more health-care practitioners and patients will have an opportunity to participate,” he highlighted.
The Pragmatica-Lung trial seeks to confirm encouraging results published by Reckamp et al in the Journal of Clinical Oncology of a randomized phase II Lung-MAP nonmatch substudy—the first lung cancer precision medicine trial supported by the NCI. The substudy involved 136 patients with advanced NSCLC who had been previously treated with chemotherapy and immunotherapy, and findings indicated that the combination of ramucirumab plus pembrolizumab may have extended survival compared with standard treatment.
Pragmatic-Lung Trial Methods and Goals
In the new study, researchers will enroll up to 700 patients aged 18 years and older with stage IV or recurrent NSCLC whose disease has progressed after previous treatment with immune checkpoint inhibitors and chemotherapy. The researchers will randomly assign the patients to receive either ramucirumab plus pembrolizumab or standard treatment—and evaluate whether the two-drug combination can potentially improve overall survival compared with standard treatment in this patient population.
“This study is designed to eliminate potential barriers to enrollment and provides a model for increasing diversity and enrollment in clinical trials,” explained Monica M. Bertagnolli, MD, Director of the NCI.
Conclusions
The researchers concluded that the pragmatic approach used in the new Pragmatica-Lung trial may be most appropriate for trials in which the drugs being studied have already been approved and their side effects are well understood.
The study will be conducted with the participation of the SWOG Cancer Research Network, the Alliance for Clinical Trials in Oncology, the ECOG-ACRIN Cancer Research Group, and NRG Oncology.
“[The] Pragmatica-Lung [trial]—with its critical public and private partnerships—reflects the innovative approaches NCI is taking to achieve the Cancer Moonshot goals, including reducing the cancer death rate by 50% within the next 25 years,” she emphasized.
The Pragmatica-Lung trial is expected to complete enrollment by the end of 2025.
Disclosure: For more information on the Pragmatica-Lung trial, visit cancer.gov.
