image: “Despite progress in treating breast cancer during the past 30 years, we still lack curative therapies for metastatic disease. EVOLVE takes a different approach to clinical research by using real-time biomarker data to adapt treatment as a tumor changes," said Lisa Carey, MD, ScM, FASCO, the study’s lead investigator and the L. Richardson and Marilyn Jacobs Preyer Distinguished Professor for Breast Cancer Research at UNC School of Medicine and the deputy director of clinical sciences at UNC Lineberger.
Credit: UNC Lineberger Comprehensive Cancer Center
UNC Lineberger Comprehensive Cancer Center has been awarded up to $28 million by the Advanced Research Projects Agency for Health (ARPA-H) to lead the development of a next-generation clinical trial for breast cancer that has spread to other parts of the body. The new trial design will adapt treatment plans in near real-time by analyzing changes in each patient’s cancer and matching it to the most promising therapy.
The Translational Breast Cancer Research Consortium Evolutionary Clinical Trial for Novel Biomarker-Driven Therapies (EVOLVE) will leverage the resources and expertise from UNC Lineberger and 14 other member institutions of the Translational Breast Cancer Research Consortium (TBCRC), a collaborative network of laboratory and clinical investigators from National Cancer Institute-designated comprehensive cancer centers committed to speeding the translation of lab discoveries into new treatments.
Lisa Carey, MD, ScM, FASCO, the L. Richardson and Marilyn Jacobs Preyer Distinguished Professor for Breast Cancer Research at UNC School of Medicine and the deputy director of clinical sciences at UNC Lineberger, is the study’s lead investigator.
“Despite progress in treating breast cancer during the past 30 years, we still lack curative therapies for metastatic disease,” Carey said. “EVOLVE takes a different approach to clinical research by using real-time biomarker data to adapt treatment as a tumor changes.”
The study will enroll up to 700 patients with metastatic breast cancer. Researchers will use tumor biopsies, blood samples, high-resolution imaging and medical records to monitor changes in a patient’s cancer. They’ll also track circulating tumor DNA (ctDNA)—fragments of tumor DNA found in the blood—and other circulating biomarkers to identify signs of treatment resistance and guide therapy choices in real time.
TBCRC EVOLVE is part of ARPA-H’s up to $142 million Advanced Analysis for Precision Cancer Therapy (ADAPT) program, which aims to transform personalized cancer care. Focused initially on breast, lung and colon cancers, ADAPT is funding 10 projects that bring together experts in biology, data science and oncology to address the challenge of treating metastatic cancer, which often changes and becomes resistant to treatment. The program has three primary goals: developing tools that combine diverse patient data, modeling treatment resistance and identifying markers that predict drug response; designing adaptive clinical trials that adjust treatment as cancer evolves; and building a shared platform for researchers and doctors to collaborate using real-time data.
Carey said ADAPT will tackle several long-standing research gaps: “We don’t yet have strong predictive biomarkers for metastatic breast cancer, and we’ve largely failed to combine different kinds of data—genomic, clinical, imaging—in a meaningful way during treatment. EVOLVE changes that.”
Metastatic breast cancer is aggressive and currently incurable. While 6-10% of patients are diagnosed with metastatic, or stage IV, disease, about 15-20% of early-stage breast cancer cases will become metastatic. With only one in three people with metastatic breast cancer surviving beyond five years, there remains a significant unmet clinical need.
“Developing better treatments for metastatic breast cancer starts with understanding how the cancer evolves over time,” Carey said. “This trial will let us act earlier, modify treatment when resistance begins—not just when symptoms return—and ultimately give patients more time, and better quality of life.”
In addition to Carey, the other principal investigators are Ian Krop, MD, PhD, Yale Cancer Center; Charles Perou, PhD, UNC Lineberger; Naim Rashid, PhD, UNC Lineberger; Eric Winer, MD, Yale Cancer Center; and Antonio Wolff, MD, Johns Hopkins Kimmel Comprehensive Cancer Center.