A novel bispecific antibody combination therapy has demonstrated significant efficacy in treating one of the most aggressive forms of breast cancer, according to new clinical trial results presented at the 2024 San Antonio Breast Cancer Symposium.
The multicenter, open-label Phase 2 study evaluated ivonescimab (SMT112), an investigational tetrameric bispecific antibody targeting PD-1 and VEGF, in combination with chemotherapy for patients with locally advanced unresectable or metastatic triple-negative breast cancer (TNBC).
Strong Efficacy Signals Across Patient Populations
The trial results showed remarkable antitumor activity, with an overall response rate (ORR) of 80.0% among all evaluable patients (n=35) at a median follow-up of 11.8 months. Two patients (5.7%) achieved complete responses, while 26 patients (74.3%) showed partial responses. Notably, the disease control rate reached 100%, with the remaining patients maintaining stable disease.
The treatment demonstrated a median progression-free survival (PFS) of 9.36 months, with 73.8% of patients remaining progression-free at 6 months and 61.3% at 9 months. The median duration of response was 7.49 months, with 72.2% of patients maintaining their response at 6 months.
Consistent Benefits Across PD-L1 Expression Levels
The therapy showed effectiveness regardless of PD-L1 expression levels. Patients with PD-L1 combined positive scores (CPS) greater than 10 achieved an 83.3% response rate, while those with CPS less than 10 showed a 79.3% response rate. Notably, patients with CPS less than 1 demonstrated an impressive 88.2% response rate, suggesting broad applicability across different patient subgroups.
Treatment Administration and Safety Profile
Study participants received ivonescimab at 20 mg/kg every two weeks, combined with either paclitaxel (90 mg/m2) or nab-paclitaxel (100 mg/m2) on days 1, 8, and 15 of each 4-week treatment cycle.
The safety profile proved manageable, with no treatment-related deaths or discontinuations. While all patients experienced some form of treatment-emergent adverse events (TRAEs), only 50% experienced grade 3 or higher events. The most common TRAEs included:
- Decreased white blood cell count (69.4% any grade, 22.2% grade ≥3)
- Decreased neutrophil count (55.6% any grade, 19.4% grade ≥3)
- Increased liver enzymes (50% any grade, 5.6% grade ≥3)
Clinical Implications
"Ivonescimab in combination with chemotherapy had a manageable safety profile and promising antitumor activity in patients with locally advanced unresectable or metastatic TNBC," stated Dr. Quchang Ouyang of Hunan Provincial Tumor Hospital, the study's lead author. The results support further evaluation of this combination as a first-line treatment for TNBC.
The study enrolled patients between 18 and 75 years with an ECOG performance status of 0 or 1 who had not received prior chemotherapy or targeted systemic therapy for TNBC. The median age of participants was 54.6 years, with 61.1% having recurrent or metastatic disease and 38.9% presenting with initial metastatic diagnosis.
