Dr Li on the Investigation of BDC-1001 in HER2-expressing Solid Tumors

Bob T. Li, MD, PhD, MPH, thoracic oncologist, early drug development specialist, physician ambassador to China and Asia-Pacific, Bobst International Center, co-director, Thoracic Liquid Biopsy Program, chief scientific officer, Memorial Sloan Kettering Cancer Center, discusses the results of a phase 1/2 study (NCT04278144) of the first-in-class immune-stimulating antibody conjugate (ADC) BDC-1001 in patients with advanced HER2-expressing solid tumors.

At the 2023 ASCO Annual Meeting, investigators shared data on the use of BDC-1001 with and without nivolumab (Opdivo) in 131 patients across multiple dose levels of the ADC. Six patients experienced confirmed partial responses, including 3 patients with colorectal cancer, and 1 each with ovarian cancer, biliary tract cancer, and salivary cancer. Three partial responses were observed for both BDC-1001 monotherapy and in combination with nivolumab.

Moreover, 12 patients achieved stable disease for at least 24 weeks, months, and numerous occurrences of tumor shrinkage by per RECIST v1.1 criteria were observed, Li says. Those patients also had a variety of HER2-expressing solid tumors, including breast cancer, gastric cancer, endometrial cancer, cervical cancer, and melanoma, Li explains.

Since the payload of BDC-1001 is a TLR7/8 agonist, the rationale for combining the agent with nivolumab was to attempt to release the T cells from the immune system with PD-1 inhibition, then potentially recruit more T cells to target the tumor, Li says. Patients received a dose of BDC-1001 ranging from 0.15 mg/kg to 20 mg/kg on dosing schedules of every 3 weeks, every 2 weeks, and every week, Li says.

Li notes that all of the patients who responded or had stable disease had HER2-positive tumors, and the study also included patients with HER2-low tumors. Encouraging anticancer activity was observed at the recommended phase 2 dose of BDC-1001 at 20 mg/kg every 2 weeks, Li continues. Fifteen patients were treated at this dose, either as a single agent and in combination with nivolumab, and the overall response rate was 27% in this group, Li concludes.