Primo N. Lara Jr, MD
Clinical trial designs are transforming dramatically in order to expedite the discovery and validation of new predictive biomarkers for patients with non–small cell lung cancer (NSCLC) and other types of solid tumors, according to a presentation by Primo N. Lara Jr, MD, at the 16th Annual International Lung Cancer Congress (ILCC) held in Huntington Beach, California.1
Once next-generation sequencing and other molecular profiling is conducted, clinical trials that randomize patients based on their genetics become more plausible. To this end, in the past 5 years, basket and umbrella protocols have been formed and the NCI has enhanced the study of exceptional responders. These steps are essential to accelerating biomarker development, Lara added.
In an umbrella trial, upfront next-generation sequencing is conducted and patients are randomized based on the results to smaller individualized arms or substudies. Each smaller group explores a targeted therapy matched to the patient’s biology. This type of trial generally explores various markers within a single histology and can grow to be very large, with 20 or more arms.
, and other markers. Immunotherapy will be administered for those without an apparent molecular driver and chemotherapy will be used as a comparator (NCT02154490).
In a basket trial, patients with various types of cancer are enrolled based on the presence of a biomarker, such as a genetic alteration or a distinct molecular signature. This style of trial takes the emphasis off histology and focuses it on the underlying genetics of each tumor. Typically, these protocols explore a single therapy across various types of cancer.
“NCI-MATCH is a classic basket study. I encourage everyone to open this trial at your center,” Lara noted. “The NCI tells us that it will take 10 to 14 days for the genetic report, which they have ensured us is feasible even in the context of an NCI trial.”
A number of basket and umbrella trials are open to enrollment, outside of the NCI-MATCH and Lung-MAP investigations. While these study designs are not new, they have begun to gain greater attention in recent years. However, in past trials that used these designs, the results were not always positive and all of the intended arms frequently had trouble enrolling, Lara cautioned. “Not all basket and umbrella strategies work out, sometimes it is a lot of resources and it doesn’t pan out,” he said. “This is not new, this is an accepted drug development pathway.”
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