Abstract P4-12-21: Efficacy and Safety of MRG002 in Prior TKI-Treated HER2 Positive Breast Cancer Patients: A Single Arm, Open Label, Multicenter, Phase II Study

Abstract Background: Human epidermal growth factor receptor 2 (HER2) positive breast cancer represented approximately 15%-20% of all breast cancers. Liver metastasis was commonly observed in patients treated with trastuzumab and tyrosine kinase inhibitor (TKI), thereby further reducing the overall survival to only 8-14 months. MRG002 is a novel antibody-drug conjugate composed of recombinant humanized anti-HER2 monoclonal antibody MAB802 and potent cytotoxic small molecule MMAE linked by the vc-linker. This study was designed to evaluate the efficacy and safety of MRG002 in liver metastases breast cancer patients after the treatment failure of trastuzumab and TKI. Method: This single-armed, open-label, multicenter, phase II study enrolled patients who had received ≥2 lines of anti-HER2 treatment (including trastuzumab and TKI) and had confirmed tumor progression during or after the most recent treatment. MRG002 was administered at a dose of 2.6 mg/kg every 3 weeks until the end of treatment, initiation of new anti-tumor therapy, withdrawal of informed consent, or death. Result: A total of 102 females were enrolled in this study, with a median age of 53 years (range: 26-73). Forty-four patients had an ECOG score of 0, and 58 scored 1. Forty-one patients (40.2%) were immunohistochemistry (IHC) 3+, and 61 (59.8%) were IHC 2+/ISH+. All patients had liver metastasis, 55 (53.9%) had bone metastasis, and 37 (36.3%) had lung metastasis. All patients had received HER2-mAb and anti-HER2-TKI drug treatment (Pyrotinib 94 cases, 92.2%). The median treatment line was 3 (range: 2-10), wherein 39 patients (38.2%) received two treatment lines, 28 (27.5%) received three, and 35 (34.3%) received ≥ four lines. As of July 19, 2024, the median follow-up time was 14.8 months (range: 0.4-27.2), and 7 patients (6.9%) had a treatment duration of nearly 2 years. The Independent Review Committee (IRC) evaluated the objective response rate (ORR) based on RECIST v1.1 as 60.8% (95% CI: 50.6-70.3), the disease control rate (DCR) as 86.3% (95% CI: 78.0-92.3), the median progression-free survival (mPFS) as 8.6 months (95% CI: 6.9-11.9), and the median duration of response (mDoR) as 9.4 months (95% CI: 6.2-16.8). The investigator assessed the ORR as 56.9% (95% CI: 46.7-66.6), the mPFS as 7.5 months (95% CI: 5.7-8.0), and the mDoR as 6.8 months (95% CI: 6.0-8.9). Subgroup analysis showed that the ORR of IHC 3+ and IHC 2+/FISH+ patients were 70.0% and 60.7%, respectively. The mPFS were 11.9 months and 7.7 months, respectively. The most common treatment-related adverse events (TRAEs) included 70.6% white blood cell count decreased, 64.7% neutrophil count decreased, 62.7% AST increased, and 54.9% ALT increased. TRAEs were mainly Grade 1-2 and recovered after treatment. TRAEs ≥ Grade 3 included 31.4% neutrophil count decreased, 13.7% white blood cell count decreased, and 6.9% peripheral neuropathy. No new safety signals were found, and the adverse events were manageable. Conclusion: MRG002 showed a potential efficacy in trastuzumab and anti-HER2-TKI treatment failed HER2-positive liver metastasis breast cancer patients with a good tolerance and safety profile. The emergence of MRG002 presented a promising treatment option for patients. Clinical trial information: NCT05263869 Citation Format: Qiang Liu, Shaohua Zhang, Yaping Yang, Quchang Ouyang, Tao Sun, Yongsheng Wang, Min Yan, Yongmei Yin, Xiaoyu Liu, Shusen Wang, Xinhong Wu, Qingyuan Zhang, Changlu Hu, Hui Li, Wei Li, Fuming Qiu, Jun Qian, Li Sun, Xiaojia Wang, Zefei Jiang. Efficacy and Safety of MRG002 in Prior TKI-Treated HER2 Positive Breast Cancer Patients: A Single Arm, Open Label, Multicenter, Phase II Study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-12-21.