PHASE ONE Funds Phase II Trial Using Biomarkers to Match Metastatic ER+ Breast Cancer Patients with Effective Treatments
PHASE ONE Foundation has awarded City of Hope’s Aritro Nath, PhD, $397,000 to fund a Phase II study aimed at improving outcomes for metastatic ER-positive breast cancer by tailoring therapies with next-gen biomarkers.
Metastatic ER-positive, HER2-negative breast cancer is a type of breast cancer that has spread to other parts of the body and is characterized by the presence of estrogen receptors (ER) and the absence of human epidermal growth factor receptor 2 (HER2) receptors.
Approximately 13% of women born in the US today will develop breast cancer, and of those, ~80% are estrogen receptor-positive.
While there are various FDA-approved treatment options available, oncologists lack an approved biomarker to determine which treatment will be most effective for each individual patient in second-line treatment for these metastatic breast tumors.
To address this critical need, Dr. Nath in collaboration with Dr. Andrea Bild at City of Hope and Dr. Rachel Layman at MD Anderson Cancer Center have developed an innovative and cutting-edge systems biology biomarker approach that leverages genomic data and an artificial intelligence algorithm. By analyzing the unique characteristics of each patient's tumor, their approach guides oncologists in selecting the most suitable treatment for optimal patient care.
In their funded clinical trial, AIM4 (“AI and Mechanistic Modeling in Molecular Medicine”) biopsy samples are taken from each patient, and the CLIA-certified biomarker assay analyzes these samples and recommends personalized treatment approaches.
Their novel biomarker, known as "ENDORSE," leverages the transcriptome of patient tumors to predict endocrine therapy response, and has demonstrated superior and consistent performance over clinical covariates and multiple published signatures. By incorporating ENDORSE and a new biomarker for mTOR inhibitor response, they aim to improve patient outcomes in terms of progression-free survival.
This trial represents a groundbreaking advancement as it steers breast cancer patients toward the most optimal treatment option after initial therapy no longer yields satisfactory results using sophisticated computational methods.
“This is a ground-breaking study and has the potential to improve care for metastatic cancer patients through sophisticated integration of data and mathematics.” –Ravi Salgia, MD, Professor and Chair, Department of Medical Oncology & Therapeutics at City of Hope.
By collecting and analyzing pre- and post-treatment tumor samples, the team also aims to identify emerging drug targets within progressing tumors. This valuable information will contribute to the continued targeting of cancer cells, even in the metastatic setting, with the goal of achieving durable responses to treatment.
“This trial represents significant progress in tailoring cancer treatment to individual patients. By understanding the unique characteristics of each patient's tumor, oncologists are equipped with the information they need to select the most effective therapies, ultimately improving patient care and outcomes.” –Marc Lebowitz, PHASE ONE Granting Committee Co-Chair
The AIM4 trial is a partnership with City of Hope and MD Anderson Cancer Center and will also collaborate with Inova Health System and Cleveland Clinic. Dr. Andrea Bild at City of Hope will contribute to the project through intellectual guidance and participation in the strategic decision-making process.