Skip to main content
Premium Trial:

Request an Annual Quote

Lung-MAP Trial Expands to Include All Advanced NSCLC Patients, Plans Liquid Biopsy Screening


SAN FRANCISCO (GenomeWeb) – The Lung Cancer Master Protocol (Lung-MAP) umbrella trial has expanded to enable all patients with advanced non-small cell lung cancer to enroll from its previous focus on advanced squamous cell lung cancer only.

In addition, researchers will begin implementing liquid biopsy as a screening protocol, initially in a pilot study to ensure that the results are comparable to tissue-based testing.

Lung-MAP is an umbrella trial that launched in 2014 and makes use of Foundation Medicine's next-generation sequencing assay to screen patients for biomarkers. Initially, the trial was open only for patients with squamous cell lung cancers, and patients with eligible biomarkers would be able to enroll in biomarker-driven drug trials. Meanwhile, patients without a biomarker would receive chemotherapy.

However, in 2016, the researchers implemented the first major update to the trial — opting to allow patients without a biomarker to receive immunotherapy. As previously reported, that change helped boost enrollment in the trial, which had been lagging.

Now, more than 1,800 patients have enrolled, and as of Feb. 2, 1,416 had biomarker results with 669 patients in ongoing or completed clinical trials, Vali Papadimitrakopoulou, a principal investigator of Lung-MAP and medical oncologist at MD Anderson Cancer Center, said.

In total, between 10 percent and 20 percent of patients who enroll in Lung-MAP end up having a biomarker that is indicative of eligibility into one of Lung-MAP's targeted therapy trials, said Roy Herbst, chief of medical oncology at Yale Cancer Center and chair of the Lung-MAP steering committee. But, even the patients who do not have a biomarker are still eligible for immunotherapy.

Papadimitrakopoulou noted that there is often a lag between when patients receive biomarker results and enrollment into a drug trial. "Ultimately, some patients choose not to enroll even though their biomarker results indicate they are eligible," she said. There's a variety of reasons for that, she added. If patients are doing well on their current therapy, they likely will not switch right away, or on the other end of the spectrum, patients may be at the end of their life and opt for palliative care.

Papadimitrakopoulou said that a number of factors led to the further expansion of Lung-MAP. The field is changing so quickly, she said, and researchers are trying to adapt to those changes.

For instance, soon after Lung-MAP launched in 2014, "data on immunotherapies began emerging," and the US Food and Drug Administration approved the first immunotherapy for lung cancer in 2015.

The original trial design assigned patients without biomarkers to receive chemotherapy, which was standard at the time. But that "quickly became non-standard" because immunotherapy became the new second-line standard therapy, Papadimitrakopoulou said. "So that change in the landscape prompted changes in the protocol."

Expanding into immunotherapy is ultimately what prompted the researchers to expand the indications from squamous cell to all non-small cell lung cancers. "By opening up the trial to all histologies, that opens up the possibility of rare driver mutation subsets that are more prevalent in adenocarcinoma and the opportunity to offer therapy to patients who belong to these rare mutation subgroups," Papadimitrakopoulou said. For instance, she said, there is now a trial being planned for patients who have a RET fusion.

Similarly, with growing evidence that screening for mutations in the blood can serve as a proxy for a tissue biopsy to profile the genomic landscape of a patient's tumor, the researchers are looking to implement a liquid biopsy screening protocol.

The Lung-MAP researchers will contract with Foundation Medicine for the liquid biopsy screening portion. The team plans to first conduct a study comparing liquid biopsy profiling to tissue-based profiling. Papadimitrakopoulou anticipates this experimental phase would last between six months and one year and would include 500 to 600 patients. She expects the study will demonstrate that the tissue and blood-based screening are comparable, as other studies have also demonstrated that, after which, the liquid biopsy assay could be used to enroll patients into the study.

"The ability to look at DNA in serum has become so precise that with time we might no longer need to biopsy tumors at great physical expense and with potential side effects to patients," Herbst said. "We're not quite there yet, but we're getting close," he said. And ultimately, he said, a liquid biopsy could be more accurate than a tissue biopsy because it may be able to better capture heterogeneity, which can be a challenge for tissue biopsies, since any given sample from one small section of the tumor may not capture the full spectrum of mutations.

Papadimitrakopoulou anticipated that eventually, when the liquid biopsy screening protocol was implemented at scale, it could help increase enrollment into Lung-MAP, since it would open up the study to patients for whom a tissue biopsy is not feasible.

In addition, she said, the assay also allows for the possibility of monitoring patients throughout the drug trial to determine whether they are responding. Such use would be dependent on the specific substudy, she noted.

The Lung-MAP team plans to continue to expand the trial to reflect the latest science, Papadimitrakopoulou said. For instance, the team is looking to incorporate at a later date biomarker-driven immunotherapy trials.

"We hope that the next generation of immunotherapy trials will be led by knowledge of the specific type of resistance that occurs from exposure to checkpoint inhibitors or the inherent resistance of tumors," she said. The idea would be to use data that's being generated from the existing trial to identify such biomarkers that could then be used as selection criteria for future immunotherapy trials.

The team is also looking to expand the types of biomarkers it analyzes to incorporate such things as tumor mutational burden and to analyze alterations that occur within the tumor microenvironment.

Already, materials are being collected that would enable RNA sequencing or immunofluorescence studies, for instance, on a case-by-case basis, she said.

"The field is moving very quickly," Herbst said, which has been one challenge for the study researchers as they have sought to adapt the trial. But the predominant challenge, he added, has been "having enough drugs and enough options" for patients.

"We need more trials like Lung-MAP that have the science built in to better understand the predictive biomarkers and find the best drug for the patient," he said.