Natera, Inc. (NASDAQ: NTRA) has announced the enrollment of the first patients in the HEROES clinical trial, a groundbreaking study that could transform treatment protocols for patients with metastatic HER2-positive breast cancer. The phase II trial will explore whether patients with no detectable molecular disease can safely discontinue anti-HER2 targeted therapy, which under current guidelines often means lifelong treatment.
The multi-center trial, supported by funding from the French Ministry of Health through the Hospital Clinical Research Program (PHRC), is being sponsored by Unicancer and developed within its French Breast Cancer Intergroup (UCBG) network. Approximately 170 patients are expected to enroll across up to 35 sites in France.
Understanding HER2+ Breast Cancer and Current Treatment Challenges
Human epidermal growth factor receptor 2 (HER2) is a protein found in cancer cells that can accelerate tumor growth when present at elevated levels. Between 15% and 20% of breast tumors are classified as HER2-positive, according to the American Cancer Society. Current standard-of-care recommendations for these patients include maintenance treatment with anti-HER2 therapies, often continuing indefinitely.
"Safely discontinuing treatment has been a long-lasting dilemma in HER2 metastatic breast cancer," explained Dr. Angel Rodriguez, senior medical director of oncology at Natera. "With Signatera monitoring, we hope oncologists can identify the patients without detectable disease who may be able to avoid additional therapy that can be costly and potentially harmful to their care."
HEROES Trial Design and Methodology
The HEROES trial (NCT06450314) will focus on metastatic HER2+ breast cancer patients who have been on anti-HER2 maintenance therapy for two or more years. The study's primary endpoint is one-year progression-free survival in patients who test negative for circulating tumor DNA (ctDNA) using Natera's Signatera test.
Key aspects of the study protocol include:
- All enrolled patients are currently receiving standard-of-care anti-HER2 targeted therapies and have been on treatment for at least two years
- Patients who test Signatera-negative at baseline will discontinue treatment and undergo regular monitoring with both Signatera testing and diagnostic imaging
- If radiological progression is confirmed or a patient becomes Signatera-positive during the trial, previous therapy will resume or a new treatment will begin
- Patients who test Signatera-positive at baseline will continue their maintenance therapy and will not proceed further in the trial
The study will also assess ctDNA dynamics and quality-of-life measures to gain deeper insights into the potential for ctDNA-guided de-escalation of treatment in patients with no detectable molecular disease burden.
Potential Impact on Treatment Paradigms
Dr. Thibault de la Motte Rouge, principal investigator of the trial and medical oncologist at the Comprehensive Cancer Centre Eugène Marquis in Rennes, France, emphasized the potential significance of the study: "The HEROES study could significantly reshape the way oncologists treat patients with metastatic HER2+ breast cancer. This could also pave the way for future research into ctDNA-guided treatment de-escalation in breast cancer."
The trial represents Natera's first clinical study using Signatera to guide de-escalation of therapy in patients with metastatic HER2+ breast cancer. If successful, the approach could spare patients from unnecessary treatment while maintaining effective disease monitoring.
About Signatera Technology
Signatera is a personalized, tumor-informed molecular residual disease test for patients previously diagnosed with cancer. The test is custom-built for each individual and uses circulating tumor DNA to detect and quantify cancer remaining in the body, identify recurrence earlier than standard-of-care tools, and help optimize treatment decisions.
The technology has been clinically validated across multiple cancer types and indications, with published evidence in over 100 peer-reviewed papers. It is currently available for clinical and research use and is covered by Medicare for patients with colorectal cancer, breast cancer, ovarian cancer, and muscle-invasive bladder cancer, as well as for immunotherapy monitoring of any solid tumor.
Unicancer's Role in Oncology Research
As the sponsor of the HEROES trial, Unicancer brings significant expertise in cancer research. The organization is the only French hospital network fully dedicated to fighting cancer and the only national hospital federation focused on oncology. It encompasses 18 cancer centers across 20 hospital sites in France, treating nearly 530,000 patients annually.
Unicancer is recognized as the leading academic promoter of clinical trials in oncology at the European level, with 106 active clinical trials promoted in 2020 and nearly 7,600 patients included. The network is also known for its flagship programs that utilize real-life data to improve knowledge and evaluate therapeutic strategies.
The HEROES trial represents an important collaboration between Natera's diagnostic technology and Unicancer's clinical research infrastructure, potentially offering a new paradigm for personalized treatment decisions in metastatic breast cancer care.
