NCI Launches ALCHEMIST

Two targeted drugs approved for metastatic lung cancer will be tested for the first time in early-stage disease to determine whether they can prevent lung cancer recurrence and prolong survival.

On August 18, the NCI launched a nationwide screening trial and two associated treatment trials. The Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials, or ALCHEMIST, will screen tumors from 6,000 to 8,000 patients with lung adenocarcinoma or a similar type of lung cancer for an EGFR mutation or ALK rearrangement following surgery. Patients will be recruited at hundreds of sites over the next 5 to 6 years through the NCI's newly formed National Clinical Trials Network (NCTN).

After surgical removal of the tumors, patients will undergo adjuvant chemotherapy with or without radiation therapy. Then, those with an EGFR tumor mutation will enter a trial testing erlotinib (Tarceva; Genentech and Astellas), while those with an ALK alteration will participate in a trial with crizotinib (Xalkori; Pfizer); they will receive either a placebo or the targeted drug and will be followed for 5 years. Researchers plan to enroll 300 to 400 patients in each of these treatment trials.

Patients whose tumors lack either alteration will also be followed for 5 years.

Such research could not be done by an individual institution or cooperative group because the population being studied is relatively small, says Pasi Jänne, MD, PhD, director of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute in Boston, MA, and co-principal investigator of the screening phase of the trial. “For rare but clinically meaningful patient populations where you may have an effective therapy, you need to work together as a group,” he says.

Indeed, lung cancer tends to be diagnosed after it has spread, and alterations in EGFR and ALK are not especially common. In the United States, about 10% of patients with lung adenocarcinoma have an EGFR mutation, and about 5% have an ALK rearrangement.

However, “most of the data we have are in patients with metastatic lung cancer, so we don't know what the prevalence may be in earlier-stage disease,” says Shakun Malik, MD, head of the NCI's Thoracic Cancer Therapeutics in the Clinical Investigations Branch.

Malik says the study also provides the opportunity to analyze tumor specimens when patients relapse to determine how those tumors became resistant to treatment—critical information, given that more than half of patients with early-stage lung cancer have a recurrence.

“There will also be advanced genomic analyses done on tumors to understand what their natural history and outcome will be,” says Jänne. “We will learn about genomics of lung cancer in general from this effort, which is exciting.”

ALCHEMIST is the second precision medicine trial to launch as part of the NCTN. Lung-MAP (Lung Cancer Master Protocol), a trial for patients with advanced squamous non–small cell lung cancer, began in June.