KN026, a HER2-directed bispecific antibody, combined with docetaxel, has demonstrated promising efficacy and a manageable safety profile as a first-line treatment for patients with HER2-positive metastatic breast cancer (MBC). Data from a Phase 2 study (NCT04165993) indicates a potential new frontline treatment option for this aggressive form of breast cancer.
The open-label, single-arm trial enrolled 57 patients who received 30 mg/kg of KN026 and 75 mg/m2 of docetaxel in 21-day cycles. The primary endpoints were objective response rate (ORR) and duration of response (DOR), while secondary endpoints included overall survival (OS), progression-free survival (PFS), clinical benefit rate (CBR), and safety.
Efficacy Results
The study reported an ORR of 76.4% (95% CI, 63.0%-86.8%) and a median PFS of 27.7 months (95% CI, 18.0 months-not reached). The CBR was 85.5% (95% CI, 73.3%-93.5%). While the median OS was not reached, the OS rates at 12, 24, and 30 months were 93.0%, 84.1%, and 78.5%, respectively.
According to Jianli Ma, PhD, of the Department of Radiotherapy at Cancer Hospital, Harbin Medical University in Heilongjiang, China, the ORR is similar to previous landmark studies. The current standard first-line treatment for HER2-positive recurrent/metastatic breast cancer, according to the National Comprehensive Cancer Network Breast Cancer Clinical Practice Guidelines, is pertuzumab plus trastuzumab and docetaxel. This combination was approved based on the CLEOPATRA trial (NCT00567190), which showed an ORR of 80.2% in the pertuzumab arm versus 69.3% in the placebo arm.
Safety Profile
Grade 3 or higher treatment-emergent adverse events (TEAEs) were observed in 63.2% of patients. No deaths were attributable to treatment with KN026 or docetaxel. The most common TEAEs were decreased white blood cell counts (63.2%), decreased neutrophil counts (61.4%), and diarrhea (36.8%).
"The safety profile of KN026 combined with docetaxel in this study was good and manageable, without novel safety concerns. This finding suggests that KN026 provides a safety advantage, particularly in terms of cardiac toxicity," the authors stated.
Trial Design and Patient Population
The Phase 2 trial enrolled 57 patients with histologically proven HER2-positive locally recurrent or metastatic breast cancer across 19 centers in China between December 30, 2019, and May 27, 2021. Patients had to have at least 1 measurable lesion at baseline, adequate organ function, and an ECOG performance status of 0 or 1. They could not have received prior systemic antitumor therapy in the metastatic setting but could have received a maximum of 2 prior lines of systemic endocrine therapy.
Future Directions
Limitations of the study include its small sample size and the lack of a control arm. To address these limitations, a randomized, controlled Phase 3 trial (NCT05838066) is planned to investigate the efficacy and safety of first-line KN026 plus HB1801 in patients with HER2-positive recurrent or metastatic breast cancer.
"These findings demonstrate the potential of KN026 plus docetaxel as a new therapeutic option for patients with HER2-positive recurrent-metastatic breast cancer. Subsequent large, randomized controlled studies are warranted to validate the clinical benefits of KN026 plus docetaxel," the authors concluded.
