KN026 and Docetaxel Show Promise as First-Line Treatment for HER2+ Metastatic Breast Cancer

KN026 (Alphamab Oncology Ltd) and docetaxel (Docefrez; Sun Pharmaceutical Industries Europe BV) demonstrated promising efficacy and a manageable safety profile as a first-line treatment for patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC), according to data from an open-label, single-arm, phase 2 study (NCT04165993).¹

Bispecific antibodies | Image Credit: © Александр Михайлюк - stock.adobe.com

HER2+ MBC is an aggressive BC subtype that is challenging to treat and associated with a high tendency of recurrence. According to the National Comprehensive Cancer Network Breast Cancer Clinical Practice Guidelines Version 1.2024, the standard first-line treatment for these patients is a combination regimen of pertuzumab (Perjeta; Genentech) with trastuzumab (Herceptin; Roche), alongside taxane chemotherapy. This approach has yielded significant objective response rates (ORRs) and favorable progression-free survival (PFS); however, improvement is needed to further extend PFS for patients.^2,3

KN026 is a recombinant humanized bispecific antibody that targets and binds to domains 2 and 4 of the HER2 protein, the same sites targeted by pertuzumab and trastuzumab, respectively. Preclinical studies have shown that KN026 delivers antitumor efficacy and has capabilities in neutralizing tumor cells that have developed resistance to standard dual therapy. In the phase 2 study, KN026 demonstrated safety and efficacy as a combination therapy, suggesting its potential application in first-line treatment regimens for patients with HER2+ MBC.³

In the trial, the researchers aimed to determine the safety and efficacy of KN026 and docetaxel. They enrolled a total of 57 patients who were assigned to receive 30 mg/kg of KN026 and 75 mg/m2 of docetaxel in 21-day cycles. The primary end points were ORR and duration of response (DOR), as well as secondary end points of overall survival (OS), PFS, clinical benefit rate (CBR), and safety.³

According to the data, patients achieved an ORR of 76.4% (95% confidence interval [CI], 63.0%-86.8%) and a median PFS of 27.7 months (95% CI, 18.0 months-not reached). The researchers reported a CBR of 85.5% (95% CI, 73.3%-93.5%). Although the median OS was not reached, the OS rates at 12, 24, and 30 months were 93.0%, 84.1%, and 78.5%, respectively.³

Grade 3 or higher treatment-emergent adverse events were observed in 63.2% patients. The researchers reported that no deaths were attributable to treatment with KN026 or docetaxel.³

The phase 2 study demonstrates that KN026 in combination with docetaxel offers a promising treatment approach for HER2+ MBC. While further studies are necessary to confirm these findings, the encouraging ORR and PFS observed in this trial highlight the potential of this combination therapy. As researchers continue to explore new treatment options, KN026 may offer a significant advancement in managing this challenging and aggressive BC subtype.

REFERENCES

1. Study of KN026 monotherapy or combination therapy in patients with metastatic breast cancer. Updated September 21, 2023. Accessed January 20, 2025. https://clinicaltrials.gov/study/NCT04165993?id=NCT04165993&rank=1

2. Study shows real-world outcomes of first-line palbociclib plus fulvestrant in HR+, HER2– metastatic breast cancer. Pharmacy Times. January 18, 2025. Accessed January 20, 2025. https://www.pharmacytimes.com/view/study-shows-real-world-outcomes-of-first-line-palbociclib-plus-fulvestrant-in-hr-her2-metastatic-breast-cancer

3. Ma J, Wang J, Xu T, et al. Efficacy and safety of KN026 and docetaxel for HER2-positive breast cancer: a phase II clinical trial. Cancer Communications. January 18, 2025. doi:10.1002/cac2.12662