Karen L. Reckamp, MD, MS
The Lung Cancer Master Protocol (Lung-MAP) is an innovative clinical trial designed to efficiently address the unmet needs of patients with advanced non–small cell lung cancer (NSCLC) following front-line therapy. This pioneering effort was the first biomarker-driven umbrella master protocol initiated by the National Cancer Institute (NCI), the NCI’s National Clinical Trials Network led by SWOG (formerly known as the Southwest Oncology Group) Cancer Research Network, the U.S. Food and Drug Administration, the Foundation for the National Institutes of Health (NIH), Friends of Cancer Research, leading academic researchers and institutions, patient advocacy groups, and industry.1
This Lung-MAP design allows multiple targeted treatments and immunotherapies to be tested simultaneously and independently of the other substudies, permitting the efficient addition of novel substudies, as new promising treatment options emerge. This umbrella trial focuses on precision medicine, and the structure enables patients’ tumors to be genetically profiled, matching them to specific substudies targeting molecular alterations or biomarkers identified in their cancer while still allowing therapeutic nonmatch substudy options for patients without genomic alterations that match any of the available Lung-MAP biomarker-driven substudies. The trial is an adaptive clinical trial platform designed to improve treatment options for patients with advanced NSCLC.
Incorporating Next-Generation Sequencing Into Standard of Care
The Lung-MAP trial was launched in 2014 for squamous NSCLC to establish an infrastructure for biomarker screening and for the rapid regulatory intent evaluation of targeted therapies at a time when standard-of-care genomic testing for this type of lung cancer was not readily available.2 The study has since provided thousands of patients access to comprehensive genomic testing, often supplied by one company’s screening platform, that they otherwise would not have had. As molecular diagnostic testing and treatment options have expanded for the disease, Lung-MAP has remained dynamic and continues to adapt to meet current patients’ needs.
In 2019, Lung-MAP 2.0 was initiated to increase trial eligibility by including all histologic types of NSCLC. Over time, as genomic testing for the cancer became mainstream, Lung-MAP’s requirement for patient tissue submission and testing using a single platform became a hindrance to enrollment since most patients already had undergone tumor molecular testing, often using a different testing panel.
With the increasing advances in next-generation sequencing over the past decade, in 2024, Lung-MAP 3.0 was introduced to expand genomic screening through a variety of commercial and academic next-generation sequencing platforms to align with current testing patterns and remove barriers to study accrual. This latest iteration of Lung-MAP allows screening for substudy entry by Clinical Laboratory Improvement Amendments (CLIA)-certified tests that are sufficiently broad, including the required tumor genetic alterations of interest (usually included in oncology-focused panels of ≥ 150 genes or whole exome). The ability to obtain a biopsy or send tissue for next-generation sequencing remains an option in the study, although it is no longer required if genomic testing was already completed. The use of liquid biopsy testing is also allowed for eligibility to a substudy if one or more gene alterations of interest are reported.
These enhancements aim to ensure a broader, more representative pool of patients into the trial, enabling researchers to study the efficacy of treatments across a variety of demographic groups. This inclusivity is essential for understanding the efficacy of treatments in a study population that reflects the real-world population of patients with advanced, previously treated NSCLC.
Addressing Cancer Care Inequities
Some operational aspects of the study have contributed to its longevity. For example, Lung-MAP is an adaptive trial, meaning it can add or close substudies over time. This flexibility enables the rapid incorporation of new scientific findings that can provide significant benefits to patients, such as emerging targeted therapies or immunotherapies, enhancing the trial’s responsiveness to advances in lung cancer research. The trial continues to focus on precision medicine using genomic testing to identify more than 150 cancer-related gene alterations and guiding patients to substudies tailored to their specific tumor profile, with the ultimate goal of increasing response rates and improving outcomes for patients.
The study remains flexible and new treatments are added as science progresses. In addition, patients without a genetic match to a therapy can participate in immunotherapy-focused nonmatch studies.
Furthermore, the Lung-MAP trial has made significant strides in addressing disparities in cancer care by increasing trial access to minority patients living in geographically diverse parts of the country. Currently, Lung-MAP has treatment sites in more than 800 centers nationwide,3 with over half of patient accruals occurring in community-based hospitals.1
With these improvements in place, Lung-MAP is poised to bring precision medicine to more patients with advanced lung cancer. Overall, Lung-MAP represents a novel approach in oncology research by allowing multiple therapies to be tested simultaneously within a single infrastructure. This trial design accelerates the pace of clinical research, aiming to bring effective, personalized treatments to patients with advanced lung cancer more quickly than traditional trials. Lung-MAP 3.0 will allow this model to continue to adapt to meet the needs of patients with lung cancer.
Improving Patient Outcomes
We remain committed to collaborating with NCI in a public-private partnership to carry on this innovative research. With representation from all four groups in the National Clinical Trials Network cooperative groups in adult cancers, including SWOG, the Alliance for Clinical Trials in Oncology, NRG Oncology, and the ECOG-ACRIN Cancer Research Group, we will build on the Lung-MAP infrastructure to efficiently evaluate the safety and efficacy of new drugs for lung cancer to achieve the primary goal of helping more patients with advanced disease live longer, higher-quality lives.
DISCLOSURE: Dr. Reckamp has served as a consultant for Amgen, AstraZeneca, Blueprint, Daiichi Sankyo, Genentech, GlaxoSmithKline, Janssen, Lilly, Mirati Therapeutics, Novartis, and Pfizer. Her institution receives research funding from Genentech, Blueprint, Daiichi Sankyo, Elevation Oncology, and Janssen. Dr. Redman reported no conflicts of interest. Dr. Waqar has served on the advisory boards of AstraZeneca, Gilead Sciences, Daiichi Sankyo, Janssen, Boehringer Ingelheim, and Pfizer. Dr. Kozono is a consultant for Genentech and Roche and receives royalties for UpToDate contributions from Wolters-Kluwer. Dr. Borghaei has served as an advisor or consultant to BMS, Lilly, Genentech, Pfizer, Merck, EMD-Serono, Boehringer Ingelheim, AstraZeneca, Novartis, Genmab, Regeneron, BioNTech, Amgen, Axiom, PharmaMar, Takeda, Mirati Therapeutics, Daiichi, Guardant, Natera, Oncocyte, BeiGene, ITEO, Jazz Pharmaceuticals, Janssen, Puma, BerGenBio, Bayer, Iobiotech, Grid Therapeutics, RAPT, Gilead Sciences, AbbVie, and Novocure; has served on scientific boards of and receives stock options from Sonnetbio, Inspirna, and Nucleai; has received honoraria from Amgen, Pfizer, Daiichi, Regeneron, Janssen, and Jazz Pharmaceuticals; has received reimbursement for travel expenses from Amgen, BMS, Merck, Lilly, EMD-Serono, Genentech, Regeneron, Mirati Therapeutics, Jazz Pharmaceuticals, and Regeneron; and is on the data and safety monitoring board of the University of Pennsylvania in the chimeric antigen receptor T-cell program supported by Takeda, Incyte, Novartis, and SpringWorks Therapeutics.
REFERENCES
1. Herbst RS, Blanke CD, Sigal EV: Novel approach to accelerate lung cancer research: Lung-MAP and the potential of public-private partnerships. Clin Cancer Res 30:29-32, 2024.
2. Redman MW, Papadimitrakopoulou VA, Minichiello K, et al: Biomarker-driven therapies for previously treated squamous non-small cell lung cancer (Lung-MAP SWOG S1400): A biomarker-driven master protocol. Lancet Oncol 21:1589-1601, 2020.
3. Blanke CD: The Front Line. Lung-MAP 3.0: The next generation. November 1, 2024. Available at www.swog.org/news-events/news/2024/11/01/lung-map-30-next-generation. Accessed January 10, 2025.
Dr. Reckampis Chair of the Lung-MAP study and Professor of Medicine and Director of Medical Oncology at Cedars-Sinai Medical Center in Los Angeles, California.
Editor’s Note: Contributors to this article also included: Mary Redman, PhD, Statistical Chair of the Lung-MAP study; Professor, Clinical Research Division, Fred Hutch Cancer Center; Lead Statistician, Lung Cancer Committee at SWOG; Saiama N. Waqar, MD, MSCI, Vice Chair of the Lung-MAP study; Professor of Medicine, Division of Oncology at the Washington University School of Medicine in St. Louis; David E. Kozono, MD, PhD, Associate Professor of Radiation Oncology, Dana-Farber Cancer Institute, Boston; Hossein Borghaei, DO, MS, Professor and Chief, Division of Thoracic Medical Oncology, Fox Chase Cancer Center, Philadelphia.
Disclaimer: This commentary represents the views of the author and may not necessarily reflect the views of ASCO or The ASCO Post.
