Trial Set to Evaluate Palbociclib for Patients with Advanced Breast Cancer Using Signatera MRD Test

October 12, 2020
Matthew Fowler

Natera announced the DARE trial examining Palbociclib to treat patients with advanced breast cancer will use its Signatera molecular residual disease test.

Natera Inc. announced that its Signatera molecular residual disease (MRD) test will be used in the DARE study evaluating palbociclib (Ibrance), which is used to treat patients with HR-positive, HER2-negative advanced breast cancer, according to a Natera press release.

The randomized, multicenter, phase 2 clinical trial plans to enroll 100 MRD-positive patients to evaluate ctDNA-guided second-line adjuvant therapy in the treatment of stage II-III, HR-positive, HER2-negative breast cancer.

"Detecting relapse before it becomes clinically symptomatic requires a test with high sensitivity and specificity," Lajos Pusztai, MD, DPhil, co-leader of genetics at the Yale Cancer Center, Yale School of Medicine and principal investigator of the trial, said in a press release. "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."

The trial will be conducted in the United States, utilizing Criterium, Inc., known as the Academic Breast Cancer Consortium (ABRCC) network, to recruit the study’s population of 100 patients. These patients will then be randomized to either continue their current adjuvant endocrine therapy regimen or begin treatment with palbociclib plus fulvestrant (Faslodex) for a period of 2 years.

The primary end point for the DARE trial is improving relapse-free survival, with secondary end points of survival and ctDNA clearance.

The Signatera MRD test is expected to be used for patient enrollment eligibility and to monitor continued therapy effectiveness after the enrollment process.

Palbociclib, a CDK4/6 inhibitor developed by Pfizer, was the first of its kind to be approved by the FDA to treat patients with HR-positive, HER2-negative advanced breast cancer in conjunction with endocrine therapy. Research has yet to determine the efficacy of this treatment in early stage disease for this cohort of patients.

"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, MBA, Natera's Senior Medical Director for Oncology. "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 testing for early relapse detection in patients with breast cancer."

The Signatera test, which was granted breakthrough device designation by the FDA in 2019, is custom-built for treatment monitoring and MRD assessment for patients previously diagnosed with cancer. The test is available for both clinical and research use and allows for a personal customized blood test tailored specifically to fit the “unique signature of clonal mutations” found in an individual’s tumor. The test is intended to detect and quantify how much cancer remains in a patient’s body rather than matching patients with any particular therapy.


Natera Announces Prospective Randomized Clinical Trial to Evaluate Palbociclib in Early Stage Breast Cancer Patients Who Test Positive with Signatera™ [news release]. San Carlos, California. Published October 2, 2020. Accessed October 12, 2020.