Natera and MEDSIR Partner on MiRaDoR Trial to Advance Genome-Guided Treatment Strategies in HR+/HER2- Breast Cancer
Natera a global leader in cell-free DNA (cfDNA) testing and precision medicine, and MEDSIR (Medica Scientia Innovation Research), an international clinical research organization specializing in oncology, today announced a strategic collaboration on the MiRaDoR study (NCT05708235). The MiRaDoR trial is a multicenter, phase II, genome-guided interventional study designed to evaluate multiple treatment strategies in patients with hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer using Natera’s Signatera™ molecular residual disease (MRD) testing platform.
The MiRaDoR trial represents a significant step forward in the application of personalized oncology approaches for early-stage breast cancer, a disease area in which recurrence remains a substantial clinical challenge despite advances in systemic therapy and disease monitoring.
Addressing an Ongoing Clinical Need in Breast Cancer
Breast cancer remains the most commonly diagnosed cancer among women worldwide. According to global cancer statistics, approximately 2.3 million new breast cancer cases were diagnosed in 2022 alone. HR+/HER2- breast cancer accounts for nearly 70% of all breast cancer diagnoses, making it the most prevalent subtype of the disease.
While survival outcomes for patients with HR+/HER2- breast cancer have improved significantly over the past two decades, recurrence continues to pose a major concern—particularly in early-stage disease, where residual microscopic disease may persist despite curative-intent surgery and adjuvant therapy. Traditional surveillance strategies rely primarily on clinical assessment and imaging, which may fail to detect recurrence until disease is clinically evident.
Emerging molecular technologies, such as circulating tumor DNA (ctDNA) testing, offer the potential to identify molecular residual disease months or even years before radiographic or symptomatic relapse occurs. By detecting tumor-specific DNA fragments in the bloodstream, ctDNA testing provides a highly sensitive and individualized approach to monitoring disease dynamics.
MiRaDoR: A Genome-Guided Interventional Trial
The MiRaDoR study is designed to assess whether treatment decisions guided by ctDNA detection and genomic profiling can improve therapeutic outcomes in early-stage HR+/HER2- breast cancer. Funded by F. Hoffmann-La Roche Ltd. and sponsored by MEDSIR, the trial will leverage Natera’s Signatera Genome platform to guide treatment selection and evaluate therapeutic response.
MiRaDoR is a multicenter, phase II clinical trial that plans to enroll up to 60 patients who have previously been treated for early-stage HR+/HER2- breast cancer and who are found to be Signatera-positive—indicating the presence of molecular residual disease—despite having no clinical or radiological evidence of disease recurrence.
Patients meeting eligibility criteria will be sequentially enrolled and assigned to one of four treatment arms designed to evaluate the effectiveness of various endocrine and targeted therapy combinations.
Study Design and Treatment Arms
All participants will initially receive standard-of-care endocrine therapy during the first 90-day period of the study, referred to as Arm A. This initial phase will serve as a reference point for evaluating molecular response to conventional treatment.
Following this period, patients will transition to one of three investigational treatment arms:
- Arm B: Giredestrant, an oral selective estrogen receptor degrader (SERD), administered as monotherapy
- Arm C: Giredestrant in combination with abemaciclib, a CDK4/6 inhibitor
- Arm D: Giredestrant combined with inavolisib, a PI3Kα inhibitor, for patients whose tumors harbor PIK3CA mutations
By stratifying patients based on molecular characteristics and therapeutic exposure, the trial aims to identify whether intensified or targeted treatment strategies result in greater reductions in ctDNA compared to standard endocrine therapy alone.
Leveraging ctDNA as a Predictive Biomarker
A central feature of the MiRaDoR trial is the use of serial ctDNA monitoring to assess treatment response in real time. Signatera is a personalized, tumor-informed assay that tracks up to 16 patient-specific tumor variants derived from whole-exome sequencing of tumor tissue.
The primary endpoint of the study is the proportion of patients who achieve either a 90% reduction or complete clearance of baseline ctDNA levels after three months of treatment in each arm. Secondary endpoints include longitudinal ctDNA dynamics and comparisons of molecular response across treatment groups.
Patients will undergo Signatera testing at baseline and at multiple predefined time points, including at 6, 9, and 12 months, followed by testing every six months until treatment discontinuation. This approach will enable investigators to closely monitor molecular response patterns over time and potentially correlate ctDNA changes with longer-term clinical outcomes.
Results from the trial may help determine whether specific therapy combinations are more effective at eliminating molecular residual disease than standard endocrine therapy, potentially informing future treatment strategies for patients at high risk of recurrence.
Advancing Precision Oncology in Clinical Trials
The MiRaDoR trial reflects a broader shift toward precision oncology, where treatment decisions are increasingly informed by molecular insights rather than solely by clinical or pathological features.
By combining Signatera Genome’s ability to detect molecular residual disease with genomic profiling, we are helping to establish a new paradigm for precision oncology clinical trials,” said Angel Rodriguez, M.D., senior medical director of oncology at Natera. “In the MiRaDoR study, investigators are not only asking whether the cancer has returned, but also gaining insight into the underlying genomic drivers—such as PIK3CA mutations—that may inform the most effective treatment approach.”
Rather than relying on a “wait-and-see” strategy, the trial seeks to proactively intervene based on molecular evidence of disease, potentially enabling earlier and more targeted therapeutic escalation.
Role of MEDSIR and Global Trial Execution
MEDSIR, the study sponsor, brings extensive experience in the design and execution of innovative oncology trials. The organization has a strong track record of conducting investigator-driven studies that integrate cutting-edge biomarkers and novel therapeutic approaches.
Enrollment for the MiRaDoR trial is currently underway, with multiple clinical sites already active in the United Kingdom. Additional site activations are expected across Europe in 2026, expanding patient access and supporting robust data collection across diverse healthcare settings.
Implications for the Future of Breast Cancer Care
If successful, the MiRaDoR trial could have far-reaching implications for the management of early-stage HR+/HER2- breast cancer. By demonstrating the feasibility and clinical value of genome-guided intervention based on ctDNA detection, the study may help pave the way for more personalized surveillance and treatment strategies in routine clinical practice.
Moreover, the trial may provide critical insights into how molecular residual disease can be used not only as a prognostic marker, but also as a predictive biomarker to guide therapy selection and optimize patient outcomes.
As the oncology community continues to explore ways to reduce recurrence risk and improve long-term survival, studies such as MiRaDoR underscore the growing role of precision medicine in transforming cancer care.
About Natera
Natera™ is a global leader in cell-free DNA and precision medicine, 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 supported by more than 325 peer-reviewed publications that demonstrate excellent performance. Natera operates ISO 13485-certified and CAP-accredited laboratories certified under the Clinical Laboratory Improvement Amendments (CLIA) in Austin, Texas, and San Carlos, California, and through Foresight Diagnostics, its subsidiary, operates an ISO 27001-certified and CAP-accredited laboratory certified under CLIA in Boulder, Colorado.
About MEDSIR
Established in 2012, MEDSIR prides itself on working closely with its strategic partners to drive innovation in oncology research. Operating in Spain and the United States, the company provides end-to-end clinical trial management, from study design to publication, with an extensive global network of experts and integrated technology to streamline the process. The company offers proof-of-concept support and a strategic approach that enables research partners to benefit from the best of both worlds: industry clinical research and investigator-driven trials. With the aim of promoting independent research worldwide, MEDSIR has formed a strategic alliance with Oncoclínicas, the leading oncology group in Brazil, which offers outstanding research potential in South America.
