Precision Medicine Umbrella Trial Expands to Include All NSCLC Patients

The large precision medicine trial known as Lung-MAP (Lung Cancer Master Protocol) has announced it will expand to patients with all non–small-cell lung cancers (NSCLC), accounting for as many as 85% of all lung cancer diagnoses in the United States. This represents a large expansion from the previous design, which allowed only patients with advanced-stage squamous cell lung cancer.

Lung-MAP launched in 2014 and has since registered more than 1,800 patients at more than 600 medical centers around the country. Patients who enroll undergo comprehensive genomic profiling, and those who qualify are matched to a specific therapy being tested based on various genetic parameters.

“The Lung-MAP trial has already proven its value by successfully completing trials with new targeted agents in selected, molecularly defined subsets of squamous cell lung cancer. This amendment to the trial will allow patients with all types of non–small-cell lung cancer to potentially benefit,” said Meg Mooney, MD, MBA, of the National Cancer Institute’s Cancer Therapy Evaluation Program, according to a press release. The trial is a public-private partnership, cosponsored by the National Cancer Institute along with various other foundations and groups, as well as pharmaceutical companies.

Along with the expansion into all types of NSCLC, the trial will also incorporate screening with liquid biopsy, and is launching two new drug sub-studies. One will test a PARP inhibitor, while the other will test the combination of a PD-L1 inhibitor and a VEGF inhibitor.

Mooney highlighted the potential of immunotherapy in particular. “Checkpoint inhibitors have produced a major advance in this refractory cancer, and Lung-MAP now intends to build on the success of these immunotherapy agents by adding new agents to further increase the effectiveness of this approach,” she said.

As more and more oncogenic driver mutations are discovered and the genomic landscape underlying many cancers is described, some experts considered the Lung-MAP approach to be a novel and important way forward that could improve over more traditional clinical trial designs. When the study began, experts led by Conor E. Steuer, MD, of the Emory University Winship Cancer Institute in Atlanta, wrote that “the goal of this clinical trial is to rapidly identify new active drugs… by utilizing a novel trial design and involving all key stakeholders in drug development in a national effort. This could serve as a paradigm for drug development for malignancies with wide molecular heterogeneity.”

More recently, the leaders of the trial published a review touting the design’s success. “Cumulative experience from this overarching, multi-institution master protocol has demonstrated centralized, real-time biomarker screening is feasible and sub-study modularity is essential for protocol adaptability in a rapidly changing treatment landscape,” wrote Vincent K. Lam, MD, and Vassiliki Papadimitrakopoulou, MD, both of the University of Texas MD Anderson Cancer Center in Houston. Papadimitrakopoulou is the lead investigator for the Lung-MAP trial.