Yale Cancer Center (YCC) researchers at Yale School of Medicine (YSM) are co-developing a clinical trial for patients with metastatic breast cancer that will ultimately adapt treatment plans to each patient in near real-time. This “evolutionary” trial will use tumor biopsies, blood samples, high-resolution imaging, and medical records to monitor changes in a patient’s cancer and guide therapy choices as the trial progresses and as tumors change.
Protein samples are being transported by an automated system in a lab – illustrative photo. Image credit: Testalize.me via Unsplash, free license
Eric Winer, MD, and Ian Krop, MD, PhD, from YCC and YSM are among the six principal investigators of the study. The research will take place across 15 institutions in the Translational Breast Cancer Research Consortium (TBCRC)—of which YCC is a part—and is supported by an up to $28 million award from the Advanced Research Projects Agency for Health (ARPA-H).
The University of North Carolina Lineberger Comprehensive Cancer Center will serve as the lead institution for the collaboration with Lisa Carey, MD, ScM, as the study’s lead investigator. Charles Perou, PhD, and Naim Rashid, PhD, of UNC Lineberger and Antonio Wolff, MD, of Johns Hopkins Kimmel Comprehensive Cancer Center are principal investigators as well.
“This is the time to extend the breast cancer research of the consortium, leveraging its collaborative network of physicians and physician-scientists,” says Winer, director of YCC, president and physician-in-chief of Smilow Cancer Hospital, and Alfred Gilman Professor of Pharmacology at YSM. “The TBCRC is uniquely positioned to enroll a diverse patient population to collect and analyze biospecimens to develop and optimize new treatments. We will also create a rich database and biorepository to help answer future clinical questions.”
Guiding cancer treatment in real time
Metastatic breast cancer is cancer that has spread from the breast to other parts of the body, and it’s difficult to treat—nearly 90% of patients with metastatic cancer will develop resistance to therapy. Between 20% and 30% of people with early-stage breast cancer will go on to develop metastatic cancer.
The study—Evolutionary Clinical Trial for Novel Biomarker-Driven Therapies (EVOLVE)—will enroll up to 700 patients with metastatic breast cancer. A key aspect of the trial will be tracking biomarkers, including fragments of tumor DNA that circulate in the blood, which could signal developing treatment resistance and inform therapy choices.
“Despite progress in treating breast cancer during the past 30 years, we still lack curative therapies for metastatic disease,” says Carey. “EVOLVE takes a different approach to clinical research by using real-time biomarker data to adapt treatment as a tumor changes.”
EVOLVE also aims to identify additional biomarkers that can be used to enable the prediction of metastasis. Currently, there are limited biomarkers that signal cancer might metastasize. The TBCRC has already made headway in this area by leveraging the immense amount of data available across the 18 partner institutions. EVOLVE will build on this work, aiming 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, chief clinical research officer at YCC and professor of medicine (medical oncology) at YSM. “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.”
High-potential, high-impact research
EVOLVE is part of ARPA-H’s Advanced Analysis for Precision Cancer Therapy program, which has committed up to $142 million to support three research areas: advancing therapy recommendation techniques, evolutionary clinical trial design, and the development of a treatment and analysis platform. The program’s ultimate goal is to be able to use biomarkers to track how tumors mutate and change and use that information to adapt cancer treatments when they do.
ARPA-H was created in 2022 with the mission to accelerate better health outcomes for all. The agency does so by funding high-potential, high-impact biomedical and health research across multiple areas. Yale researchers are involved in several collaborative teams and projects.
In 2023, Richard Edelson, MD, Anthony N. Brady Professor of Dermatology at YSM, was co-principal investigator of a multi-institution collaboration that received the first ARPA-H award. The project—which is led by Emory University and includes researchers at YSM and the University of Georgia—is using mRNA to direct the natural immune system toward fighting cancer, lupus, and emerging infections.
In 2024, ARPA-H awarded Todd Constable, PhD, and a YSM team an award to develop a more affordable method for breast magnetic resonance imaging, one that costs 10 times less than the current standard and can be used in community settings.
Across the projects it supports, ARPA-H empowers groups of researchers using a variety of approaches to tackle a specific problem.
“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. And at present, over 40,000 individuals in the U.S. lose their lives to breast cancer every year.”
Source: Yale University