KN026 and KN046 Combination Therapy Shows Promise in HER2+ Breast Cancer

In a significant advancement in the treatment of HER2-positive breast cancer, the combination therapy of KN026 and KN046 has demonstrated durable responses and a manageable safety profile in patients who have previously undergone treatment. The findings, published in the *Clinical Cancer Research* journal, stem from a Phase 2 trial (NCT04521179) involving 36 evaluable patients. The study revealed a confirmed objective response rate (ORR) of 47.2% and a clinical benefit rate (CBR) of 50.0%, indicating promising efficacy for this chemotherapy-free regimen.

According to Dr. Jieqiong Liu, MD, lead author and researcher at the Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, "The chemotherapy-free treatment of KN026 plus KN046 as second- or later-line therapy in patients with advanced HER2-positive breast cancer had a favorable efficacy with a comparative safety profile." The median progression-free survival (PFS) reached 5.6 months, while the overall survival (OS) was recorded at 25.7 months, with a 12-month OS rate of 63.9%.

The trial was designed to evaluate the safety, efficacy, and tolerability of the bispecific antibodies KN026 and KN046. Patients enrolled in the study were 18 to 75 years old, had HER2-positive cancer defined by specific immunohistochemistry criteria, and had experienced disease progression following at least one prior HER2-targeted therapy. Notably, patients without liver metastases exhibited a higher confirmed ORR of 66.7%. These results have spurred interest in further randomized controlled trials to validate the findings.

Subgroup analyses showed that among patients with fewer prior therapies, the response rates were particularly encouraging. However, treatment-related adverse events (TRAEs) were prevalent, occurring in 94.4% of participants, though most were manageable. The most frequent TRAEs included infusion-related reactions and elevated liver enzymes, with no treatment-related deaths reported. Dr. Liu emphasized the necessity for ongoing research to fully understand the long-term implications of this treatment approach.

The trial's findings echo a growing trend in oncology towards targeted therapies, particularly in breast cancer, where advancements in HER2-targeted treatments have significantly improved patient outcomes. As the medical community continues to explore innovative treatment combinations, KN026 and KN046 may play a pivotal role in shaping future therapeutic strategies for HER2-positive breast cancer patients, especially those who have exhausted other treatment options.

The research team anticipates that continued exploration and validation of these findings through future studies will further establish the role of KN026 and KN046 in therapeutic regimens for HER2-positive breast cancer, potentially offering new hope to patients facing advanced disease stages.