The cancer research community is moving forward in its efforts find more effective treatment for patients with lung cancer. Current clinical trials are taking innovative approaches to how therapies for both advanced and early-stage lung cancers are studied. The goal of each study is to improve access to promising drugs for patients with more efficient clinical trials processes.
These two trials include the Lung Cancer Master Protocol (Lung-MAP) trial and the Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials (ALCHEMIST). Lung-MAP is studying therapy for advanced lung cancer (squamous cell, specifically), and the ALCHEMIST trials are studying treatment in early-stage disease.[1], [2]
The Lung-MAP Trial
In Lung-MAP (Lung-MAP.org), researchers with several public institutions, including the National Cancer Institute (NCI), are working with pharmaceutical companies to study treatment for advanced squamous cell lung cancer. Though only a fraction (about a quarter) of all lung cancer diagnoses as squamous cell, it’s an important area of research, as there are few treatment options for these patients.
Lung-MAP will evaluate several investigational treatments and match patients with the therapy most likely to benefit them. Participants will undergo genomic profiling—a type of testing that provides information about all the genes in an organism, including variation, gene expression, and the way genes interact with each other and the environment. The drugs studied in Lung-MAP are designed to target genomic alterations involved in the growth of cancer, and researchers will use genomic profiling to match patients with the therapy designed to target the particular genomic alterations that their cancer expresses.
One of the goals of Lung-MAP is that by directly matching patients to the therapy most promising for their particular disease, patients are more likely have access to promising treatment.
As understanding of squamous cell lung cancer grows, researchers are increasingly aware that one squamous cell disease can be very different on a genomic level from the next. These distinct alterations might be most effectively treated with different targeted therapies. Lung-MAP includes five different therapy arms so that participants can be matched with the treatment most likely to work for them.
This more comprehensive approach marks a change in the typical clinical trial model for targeted therapies, in which separate studies for the same disease focus on particular genomic abnormalities and treatments. Potential participants are tested for that genomic biomarker (a molecule that is a sign of a normal or abnormal process or of a condition or disease), and only individuals who test positive are enrolled in the study. As a result, many patients are left out of each trial and—with multiple, separate trials—overall progress in treatment development is made less efficient.
In Lung-MAP, however, everyone who’s tested will be eligible for a therapy. And several treatments for advanced squamous cell lung cancer will be evaluated under one protocol in an effort to accelerate safe drug development.
The ALCHEMIST Lung Cancer Trials
The ALCHEMIST trials include three clinical trials for patients with certain types of early-stage non-small cell lung cancer (NSCLC) that has been treated surgically. The trials will study targeted therapies that have been approved for advanced lung cancer but are currently not approved for treatment of patients with early-stage disease.
Each participant will be matched with the targeted therapy most likely to work for them. In the screening component of the ALCHEMIST trials, researchers will screen tumor samples for specific genetic mutations (abnormalities in the DNA sequence of a cell that are passed from parents to children) that may be involved in the development of cancer. Once specific mutations are identified, these early-stage NSCLC patients will be assigned to one of two different treatment arms, where they’ll receive drugs approved to target their mutation in advanced lung cancer. The ALCHEMIST trials will assess whether these treatments are safe and effective in early-stage NSCLC that has been surgically removed.
Researchers will look for genetic mutations in two genes thought to drive cancer growth, ALK and EGFR. Therapies are available that target both of these mutations. Patients who have one of these alterations will then be referred to one of the two treatment trials. One study is evaluating the drugs Xalkori® (crizotinib) and the other Tarceva® (erlotinib)—both as treatment after surgery for patients with early-stage NSCLC. Patients will be monitored for recurrence and survival.
Researchers with the ALCHEMIST trials hope that identifying genetic mutations in early-stage lung cancer patients and treating them with the appropriate targeted therapies will help more patients get effective treatment.
More information on each component of the ALCHEMIST trials is available at:
ALCHEMIST Screening component: http://www.cancer.gov/clinicaltrials/NCT02194738
ALCHEMIST EGFR Treatment component: http://www.cancer.gov/clinicaltrials/NCT02193282
ALCHEMIST ALK Treatment component: http://www.cancer.gov/clinicaltrials/NCT02201992
References:
[1] Lung-MAP Launches: First Precision Medicine Trial From National Clinical Trials Network [press release]. The National Cancer Institute. Available at: http://www.cancer.gov/newscenter/newsfromnci/2014/LungMAPlaunch. Accessed December 19, 2014.
[2] The ALCHEMIST Lung Cancer Trials. The National Cancer Institute website. Available at: http://www.cancer.gov/clinicaltrials/noteworthy-trials/alchemist. Accessed December 19, 2014.