Signatera, Natera’s personalized test to detect residual signs of cancer in people with solid tumors, will be used in an upcoming Phase 2 trial as a tool to identify patients with early HR-positive (hormone receptor-positive), HER2-negative (human epidermal growth factor 2-negative) breast cancer who are at high risk of cancer relapse.
The test also will be used to monitor the response of participants who do test positive for signs of residual disease to a combination therapy of Pfizer’s Ibrance (palbociclib) and AstraZeneca’s Faslodex (fulvestrant).
The trial, called DARE (NCT04567420), will be carried out in the U.S. at the Yale Cancer Center in Connecticut, through Criterium, doing business as Academic Breast Cancer Consortium (ABRCC). Enrollment is not yet active; more information will become available here.
“Detecting relapse before it becomes clinically symptomatic requires a test with high sensitivity and specificity,” Lajos Pusztai, MD, PhD, the trial’s principal investigator and a professor of medical oncology at Yale University, said in a press release.
Of note, sensitivity is a test’s ability to identify people with a disease (true positives), while specificity refers to its ability to detect individuals without the disorder (true negatives).
“Signatera enables us to confidently identify patients with molecular relapse when the disease burden is so low that it is undetectable with imaging. The trial will test if early intervention at this stage could delay or avert a clinical relapse,” said Pusztai, also co-leader of the genetics, genomics and epigenetics research program at the Yale Cancer Center.
A patient-tailored, personalized test, Signatera is designed to detect small DNA fragments from tumor cells circulating in the blood, called circulating tumor DNA (ctDNA).
The presence of ctDNA is a sign of molecular residual disease, as it means that cancer cells are still present despite treatment. These cells are the cause of cancer relapse, but often remain undetected during standard imaging analyses.
At the enrollment stage, Signatera will be used to identify 100 patients with stage 2 or 3 HR-positive and HER2-negative breast cancer undergoing treatment with hormone therapy who show signs of residual disease.
The participants will then be randomly selected to continue their current hormone therapy or start treatment with Ibrance plus Faslodex for two years.
The trial’s main goals include assessing the prevalence of ctDNA in patients during the screening phase, and determining if the combination therapy of Ibrance and Faslodex may be superior to standard hormone therapy at prolonging the time patients live without having a relapse.
Ibrance is an oral medication that works by blocking the activity of cyclin-dependent kinase (CDK) 4/6, enzymes that regulate cell proliferation and growth, and are often overactive in breast cancer.
The medication is approved in the U.S. to treat patients with HR-positive and HER2-negative advanced breast cancer, when given alongside hormone therapy. However, it is still unknown whether it also may be effective in treating patients with early stage breast cancer.
“We are delighted to collaborate with Yale and Criterium/ABRCC to investigate the efficacy of palbociclib in patients with detectable residual disease based on Signatera,” said Alexey Aleshin, MD, senior medical director for oncology at Natera.
“This is the second clinical trial using Signatera to evaluate the efficacy of a CDK4/6 inhibitor, and it heralds the significant utility of personalized MRD [molecular residual disease] testing for early relapse detection in patients with breast cancer,” Aleshin said.