Dr Cortés on Developing CD47 as a Biomarker in Pretreated HER2+ Breast Cancer

“Now we are trying to develop a biomarker to be combined with HER2 to optimize treatment.”

Javier Cortés, MD, PhD, head of the International Breast Cancer Centre, discussed the single-arm phase 2 ASPEN-09-03 trial (NCT07007559) evaluating the CD47-blocking agent evorpacept (ALX148) plus trastuzumab (Herceptin) and physician’s choice of chemotherapy in patients with HER2-positive metastatic breast cancer previously treated with fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu), as well as how CD47 could emerge as a biomarker for use after HER2 detection to guide later-line therapy.

In ASPEN-09-03, all patients will receive the 3-drug combination of evorpacept, trastuzumab, and chemotherapy, Cortés said. A defining feature of the study is the requirement, wherever feasible, for a baseline tumor biopsy, so investigators can assess patients’ CD47 expression, he explained. Evorpacept is a high-affinity CD47 blocker with an inactive Fc region designed to enhance antibody-dependent cellular phagocytosis by disrupting the CD47–SIRPα “don’t eat me” signal, complementing trastuzumab therapies. ASPEN-09-03 is enrolling patients whose disease has progressed after T-DXd. 

CD47 is a marker of resistance, according to Cortés, and a fresh baseline biopsy is essential because its expression in a tumor can change over time. For example, a tumor that lacked the biomarker 2 years earlier may express CD47 after anti-HER2 therapy, he noted, so without a baseline biopsy, the biomarker strategy would not be optimized.

If ASPEN-09-03 is positive, CD47 could become a second biomarker for use after HER2 detection in pretreated patients, helping with treatment decision-making regarding subsequent lines of therapy, Cortés said. Today, patients with HER2-positive disease are largely treated the same way in the second line and beyond, he noted, but a validated CD47 biomarker combined with HER2 could instead allow treatment to be tailored to the individual tumor. Together, he concluded, these advances could help patients with HER2-positive breast cancer live longer and, he hopes, live better.