Efficacy and safety of MRG002 monotherapy in treating patients with locally advanced or metastatic breast cancer with low HER2 expression: A multi-center, non-randomized, open-label phase II clinical trial.

BACKGROUND

MRG002 is a novel antibody-drug conjugate (ADC) targeting human epidermal growth factor receptor 2 (HER2), with a monomethyl auristatin E (MMAE) payload. This multicenter, non-randomized, open-label Phase II study was conducted to evaluate the efficacy and safety of MRG002 in patients with locally advanced or metastatic breast cancer with low HER2 expression.

METHODS

Eligible patients had locally advanced or metastatic breast cancer with low HER2 expression (including both hormone receptor-positive and -negative subtypes) and had failed at least one line of standard therapy. MRG002 was administered intravenously at 2.6 mg/kg every 3 weeks. Imaging evaluations were performed every 6 weeks until treatment completion, initiation of a new anti-tumor therapy, withdrawal of informed consent, or death.

RESULTS

As of the cutoff date (April 30, 2024), 56 patients were enrolled across 14 centers in China. The confirmed objective response rate (ORR) assessed by the Independent Review Committee (IRC) was 39.3 % (22 patients; 95 % CI, 26.5 %-53.2 %), and the disease control rate (DCR) was 73.2 % (95 % CI, 59.7 %-84.2 %). Median progression-free survival (PFS) was 5.8 months (95 % CI, 5.5-7.3). Overall survival (OS) data were immature; the 12-month OS rate was 79.9 % (95 % CI, 69.2 %-87.3 %). The most common Grade 3-4 treatment-related adverse events (TRAEs) occurring in ≥ 5 % of patients included decreased neutrophil count (17.9 %), decreased white blood cell count (8.9 %), and peripheral neuropathy (7.1 %). One patient experienced Grade 2 interstitial lung disease, and no drug-related deaths occurred.

CONCLUSIONS

MRG002 demonstrated a manageable safety profile and promising anti-tumor activity in patients with locally advanced or metastatic breast cancer with low HER2 expression.