Natera Announces Enrollment of First Patients in HEROES Clinical Trial for Metastatic HER2+ Breast Cancer
Natera, Inc., a leader in cell-free DNA and genetic testing, has announced the enrollment of the first patients in the HEROES clinical trial. This pivotal multi-center, phase II study is designed to explore the potential for de-escalating or discontinuing anti-HER2 targeted therapy in patients with metastatic HER2+ breast cancer. Supported by funding from the French Ministry of Health through the Hospital Clinical Research Program (PHRC), the trial is sponsored by Unicancer and is being developed within the Unicancer French Breast Cancer Intergroup (UCBG) network.
What is HER2+ Breast Cancer?
Human epidermal growth factor receptor 2 (HER2) is a protein found on the surface of certain cancer cells. When present in higher-than-normal amounts, it can cause these cancer cells to grow rapidly. Around 15% to 20% of breast cancers are classified as HER2+, meaning they have excessive HER2 protein levels that contribute to tumor growth.
For patients with metastatic HER2+ breast cancer, current treatment guidelines recommend the use of anti-HER2 therapies to slow down or halt the progression of the disease. In many cases, these patients are advised to remain on the medication indefinitely. However, the need for lifelong treatment can result in significant side effects, high costs, and potential long-term health risks.
The HEROES Clinical Trial: A New Approach to Treatment
The HEROES (NCT06450314) trial will enroll approximately 170 patients with metastatic HER2+ breast cancer who have already discontinued anti-HER2 maintenance therapy. The trial’s primary objective is to assess one-year progression-free survival in a cohort of patients who are Signatera-negative at baseline, meaning no detectable molecular disease burden. This approach focuses on using circulating tumor DNA (ctDNA) monitoring to guide treatment de-escalation.
Key aspects of the HEROES study include:
- Baseline Treatment: All patients at the start of the trial are currently receiving standard-of-care (SOC) anti-HER2 therapy and have been on treatment for at least two years.
- Signatera-Negative Patients: Patients who are Signatera-negative at baseline (meaning no detectable ctDNA) will stop their anti-HER2 therapy and will be monitored through serial Signatera testing and imaging. If any radiological progression or reappearance of ctDNA occurs, they will resume their previous therapy or switch to a new treatment.
- Signatera-Positive Patients: Patients who are Signatera-positive at baseline (meaning detectable ctDNA) will continue on their maintenance therapy and will not participate further in the trial.
The study also aims to examine ctDNA dynamics and quality-of-life measures to gain insights into whether ctDNA-guided de-escalation is feasible and safe for patients with no detectable molecular disease burden.
Potential Impact on Treatment Strategy
Dr. Thibault de la Motte Rouge, the principal investigator of the trial, emphasized the potential for the HEROES study to transform the management of metastatic HER2+ breast cancer. “This study could significantly change how oncologists treat patients with metastatic HER2+ breast cancer,” said Dr. de la Motte Rouge, who is a medical oncologist at the Comprehensive Cancer Centre Eugène Marquis in Rennes, France. “It could also pave the way for future research into ctDNA-guided treatment de-escalation in breast cancer.”
The use of ctDNA testing in monitoring disease progression could lead to more personalized treatment strategies, potentially allowing patients who are in remission to safely discontinue therapy, reducing unnecessary treatment and associated side effects. This approach may also help reduce healthcare costs by minimizing prolonged and unnecessary medication use.
Natera’s Role and Future Outlook
Natera’s proprietary Signatera test, a personalized ctDNA test, plays a crucial role in the HEROES trial by providing sensitive and accurate monitoring of molecular disease burden. The trial’s findings could change how clinicians approach metastatic HER2+ breast cancer treatment, specifically by identifying patients who may benefit from reducing or discontinuing therapy. This would allow for safer, more effective treatment plans that align with each patient’s unique needs.
Dr. Angel Rodriguez, Senior Medical Director of Oncology at Natera, expressed excitement over the trial’s progress. “We are excited to see the first patients enrolled in the HEROES clinical trial,” he said. “Safely discontinuing treatment has been a longstanding dilemma in metastatic HER2+ breast cancer. 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.”
The results of this trial could not only provide valuable insights into the potential for treatment de-escalation but also contribute to broader advancements in personalized cancer care. As the trial progresses, Natera and its partners hope to establish a new standard in breast cancer treatment that balances efficacy with patient well-being.
Conclusion
The HEROES clinical trial marks an important step in understanding how molecular testing can guide the treatment of metastatic HER2+ breast cancer. By using ctDNA monitoring to potentially reduce or stop therapy in patients with no detectable disease, this trial could offer new hope for patients seeking more personalized and less aggressive treatment options. With the first patients now enrolled, the HEROES study is poised to reshape the landscape of HER2+ breast cancer care and bring forward new opportunities for more precise, effective, and patient-centered treatment strategies.
About Signatera
Signatera is a personalized, tumor-informed, molecular residual disease test for patients previously diagnosed with cancer. Custom-built for each individual, Signatera uses circulating tumor DNA to detect and quantify cancer left in the body, identify recurrence earlier than standard-of-care tools, and help optimize treatment decisions. The test is 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. Signatera has been clinically validated across multiple cancer types and indications, with published evidence in over 100 peer-reviewed papers.
About Natera
Natera™ is a global leader in cell-free DNA and genetic testing, dedicated to oncology, women’s health, and organ health. We aim to make personalized genetic testing and diagnostics part of the standard of care to protect health and inform earlier, more targeted interventions that help lead to longer, healthier lives. Natera’s tests are validated by more than 250 peer-reviewed publications that demonstrate high accuracy. Natera operates ISO 13485-certified and CAP-accredited laboratories certified under the Clinical Laboratory Improvement Amendments (CLIA) in Austin, Texas, and San Carlos, California. For more information, visit www.natera.com.
About Unicancer
Unicancer is the only French hospital network 100% dedicated to the fight against cancer and the only national hospital federation dedicated to oncology. It brings together 18 Centres de lutte contre le cancer (CLCC), private non-profit healthcare establishments, spread over 20 hospital sites in France, as well as two affiliated member establishments. The CLCCs treat nearly 530,000 patients per year (in short stays, home hospitalisation and outpatient procedures).
Unicancer is also 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. Unicancer also runs flagship programmes that use real-life data to improve knowledge and the evaluation of therapeutic strategies, particularly through the ESME platforms, which bring together data from more than 76,000 cancer patients.
Recognised as a leader in research in France, the Unicancer network enjoys a worldwide reputation with the production of one third of French publications of international scope in oncology (source: bibliometric study/Thomson Reuters). In total, nearly 700 clinical trials (inclusions or follow-ups) were promoted in 2020 by the Unicancer network, more than 14% of CLCC patients are included in clinical trials and more than half of the PHRCs are allocated to CLCCs. The 18 CLCCs and the Unicancer R&D department are ISO 9001:2015 certified for their clinical research.
