The UNC Lineberger Comprehensive Cancer Center has secured $28 million from the Advanced Research Projects Agency for Health (ARPA-H) to launch a groundbreaking clinical trial that could transform how metastatic breast cancer is treated. The trial, called "Evolutionary Clinical Trial for Novel Biomarker-Driven Therapies" (EVOLVE), will adapt treatment plans in near real-time by analyzing changes in patients' cancers and matching them to the most promising therapies.
"This has the potential to be practice-changing," said Bill Schaller, the Lineberger Center's director of communications. "This trial could pave the way for a new, more dynamic approach to treatment."
Addressing an Urgent Medical Need
Metastatic breast cancer remains a formidable challenge in oncology. Between 15 and 20 percent of early-stage breast cancer cases will become metastatic, and only one in three people with metastatic breast cancer survive beyond five years. Currently, metastatic breast cancer is incurable, with nearly 90% of patients developing resistance to therapy.
"Despite progress in treating breast cancer during the past 30 years, we still lack curative therapies for metastatic disease," said Dr. Lisa Carey, the deputy director of clinical sciences at the Lineberger Center and the study's lead investigator. "EVOLVE takes a different approach to clinical research by using real-time biomarker data to adapt treatment as a tumor changes."
Revolutionary Trial Design
EVOLVE will enroll up to 700 patients with metastatic breast cancer across 15 institutions in the Translational Breast Cancer Research Consortium (TBCRC). The trial represents a fundamental shift from traditional clinical approaches by continuously monitoring tumor evolution through multiple data sources including tumor biopsies, blood samples, high-resolution imaging, and medical records.
A key innovation involves tracking biomarkers, particularly fragments of tumor DNA that circulate in the blood, which could signal developing treatment resistance and inform therapy choices. This approach allows clinicians to intervene earlier in the treatment process.
"This trial will let us act earlier, modify treatment when resistance begins – not just when symptoms return," Carey explained, "and ultimately give patients more time, and better quality of life."
Collaborative Research Network
The study brings together leading cancer researchers from multiple institutions. Eric Winer, MD, director of Yale Cancer Center and president of Smilow Cancer Hospital, and Ian Krop, MD, PhD, chief clinical research officer at Yale Cancer Center, serve as principal investigators alongside Carey. Additional principal investigators include Charles Perou, PhD, and Naim Rashid, PhD, of UNC Lineberger, and Antonio Wolff, MD, of Johns Hopkins Kimmel Comprehensive Cancer Center.
"This is the time to extend the breast cancer research of the consortium, leveraging its collaborative network of physicians and physician-scientists," says Winer. "The TBCRC is uniquely positioned to enroll a diverse patient population to collect and analyze biospecimens to develop and optimize new treatments."
Biomarker Discovery and Validation
Beyond adapting existing treatments, EVOLVE aims to identify additional biomarkers that can predict metastasis. Currently, there are limited biomarkers that signal when cancer might spread to other parts of the body. The trial will build on previous TBCRC work to identify and validate biomarkers for treatment sensitivity and resistance.
"Collecting and analyzing biospecimens to develop, validate, and test biomarkers and pair them with the proper therapy is critical," says Krop. "We can maximize the impact of the next generation of cancer-fighting drugs when we use the results from clinical trials to inform how the therapies can be refined to benefit the most patients."
ARPA-H's Precision Cancer Initiative
EVOLVE is part of ARPA-H's Advanced Analysis for Precision Cancer Therapy (ADAPT) program, which has committed up to $142 million to support research in advancing therapy recommendation techniques, evolutionary clinical trial design, and treatment platform development. The Lineberger trial is one of 10 projects receiving funding through ADAPT.
The program's ultimate goal is to use biomarkers to track how tumors mutate and change, then use that information to adapt cancer treatments accordingly. ARPA-H, created in 2022, focuses on funding high-potential, high-impact biomedical research to accelerate better health outcomes.
Clinical Impact and Future Implications
The trial addresses a critical gap in cancer care, where over 40,000 individuals in the U.S. lose their lives to breast cancer annually. By enabling real-time treatment adaptation, EVOLVE could significantly improve outcomes for patients with metastatic disease.
"We are grateful to have been trusted with this opportunity and look forward to getting the work underway," says Winer. "Great progress in the treatment of breast cancer has been made in recent years, but there is still so much more work to do if we are going to minimize and ultimately eliminate mortality from breast cancer."
The research will also create a comprehensive database and biorepository to support future clinical investigations, potentially benefiting cancer research beyond the immediate scope of the trial.
