A unique public-private collaboration among the National Cancer Institute (NCI), part of the National Institutes of Health, SWOG Cancer Research, Friends of Cancer Research (Friends), the Foundation for the National Institutes of Health (FNIH), five pharmaceutical companies (Amgen, Genentech, Pfizer, AstraZeneca, and AstraZeneca's global biologics R&D arm, MedImmune), and Foundation Medicine today announced the initiation of the Lung Cancer Master Protocol (Lung-MAP) trial.
Lung-MAP is a multi-drug, multi-arm, biomarker-driven clinical trial for patients with advanced squamous cell lung cancer. Squamous cell carcinoma represents about a quarter of all lung cancer diagnoses, but there are currently few treatment options beyond surgery for the disease. The trial will use genomic profiling to match patients to one of several different investigational treatments that are designed to target the genomic alterations found to be driving the growth of their cancer. This innovative approach to clinical testing should both improve access to promising drugs for patients and ease the significant recruitment and infrastructure burdens on researchers involved in traditional clinical trials.
"This diverse, collaborative approach, with support from leading lung cancer advocacy organizations, helps to ensure that the needs of patients, clinicians, developers, and regulators are all considered in the design and operation of the trial," said Dr. Ellen Sigal, Chair & Founder of Friends of Cancer Research.
The trial will initially test five experimental drugs—four targeted therapies and an anti-PD-L1 immunotherapy. It is anticipated that between 500 and 1000 patients will be screened per year for over 200 cancer-related genes for genomic alterations. The results of this test will be used to assign each patient to the trial arm that is best matched to their tumor's genomic profile.
"Lung-MAP represents the first of several planned large, genomically-driven treatment trials that will be conducted by NCI's newly formed National Clinical Trials Network (NCTN)," said Jeff Abrams, M.D., Associate Director of NCI's Cancer Therapy Evaluation Program. "The restructuring and consolidation of NCI's large trial treatment program, resulting in the formation of the NCTN, is quite timely, as it now can offer an ideal platform for bringing the benefits of more precise molecular diagnostics to cancer patients in communities large and small."
"Squamous cell lung cancer, like many other neoplasms, is increasingly recognized as consisting of a host of relatively rare genomic subsets, each of which may require treatment with a different targeted drug," said Dr. Charles Blanke, Chair of SWOG Cancer Research. "The Lung-MAP S1400 trial models a way to efficiently study a large number of these rare squamous cell subsets under one master protocol."
Lung-MAP aims to establish a model of clinical testing that more efficiently meets the needs of both patients and drug developers. Whereas a typical clinical trial for a targeted therapy tests each potential patient for a single biomarker and enrolls only a portion—sometimes a very small portion—of patients tested, Lung-MAP will simultaneously test patients for many biomarkers including selected base substitutions and small in/dels, gene fusions, and amplifications in order to assess compatibility with several different experimental treatments. All patients tested will then be enrolled into one of Lung-MAP's five trial arms.
"Traditional clinical trials have long imposed significant recruitment and infrastructure burdens on researchers and patients, with frustratingly slow results," said Maria Freire, Ph.D., President and Executive Director of the FNIH. "This master protocol will allow multiple enrollees to be tested once and assigned to a treatment most likely to work for them, rather than separate tests for separate trials with most patients ineligible. This strategy will validate biomarkers and facilitate drug development in one infrastructure, to more rapidly provide safer and more effective treatments to patients."
Lung-MAP will make it easier for patients and researchers to find one another. It will also be more flexible than traditional clinical trial models. Where typical clinical trials require the development of new protocols for each new drug tested, Lung-MAP uses a single "master protocol," which can be amended as needed as drugs enter and exit the trial, preserving infrastructure and patient outreach efforts.
The trial will be conducted at over 200 medical centers by NCI's NCTN, led by SWOG, and partly funded by NCI through its Cancer Therapy Evaluation Program. Significant additional funding will be provided by the participating companies as part of a partnership managed by FNIH that also involves the Food and Drug Administration (FDA), Friends, and other patient advocacy organizations. The trial infrastructure is capable of testing as many as 5-7 additional drugs over the next 5 years, and will cost up to $160 million.
In addition to the individuals quoted above, key members of the Lung-MAP trial leadership also include: David Gandara, Chair, Lung Committee, SWOG and director The Thoracic Oncology Program at UC Davis Cancer Center; Roy Herbst, Ensign Professor of Medicine and Chief of Medical Oncology at Yale Cancer Center; Vali Papadimitrakopoulou, Professor, Department of Thoracic/Head and Neck Medical Oncology at MD Anderson; and David Wholley, Executive Director, The Biomarkers Consortium, FNIH.
Said Vincent Miller, M.D., Chief Medical Officer of Foundation Medicine, "Squamous cell carcinoma of the lung is a deadly cancer killer and like many common solid tumors, analysis of no one or even several genes provides a sufficiently comprehensive characterization of the actionable alterations present in a population of patients to ensure a high screen hit rate when evaluating patients for a targeted therapy approach. Rather, multiple genes often altered by one or more classes of DNA changes and often co-occurring are unpredictably altered in any given patient. The comprehensive, broad based nature of FoundationOne testing allowed us to be uniquely suited to provide reliable results across an unprecedented broad swath of predictive biomarkers in a clinically relevant turnaround time to attract multiple interested pharma partners with distinct therapeutic targets".
For more information of Lung-MAP, visit www.Lung-MAP.org.