Abstract PS8-05: ACE-Breast-08: a phase I study of ARX788, a novel anti-HER2 antibody-drug conjugate, in patients with TKI pretreated HER2 positive advanced breast cancer

Le résumé fourni par la source

Abstract Background: Anti-HER2 TKI-resistant, advanced breast cancer has a poor prognosis with limited treatment options. ARX788 is a next-generation antibody-drug conjugate (ADC) of HER2 monoclonal antibody site-specifically conjugated with a potent cytotoxic tubulin inhibitor (AS269). This phase Ⅱ study aimed to evaluate the efficacy and safety of ARX788 in patients with HER2 positive advanced breast cancer previously treated with trastuzumab and anti-HER2 tyrosine kinase inhibitor (TKI). Methods: This multicenter, open and single-arm study was conducted in 13 centers in China. Eligible patients were aged between 18 and 75 years, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, had HER2 positive (FISH+ or IHC3+) unresectable or metastatic breast cancer pretreated with trastuzumab and anti-HER2 TKI, and had at least one measurable lesion per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). All patients were received ARX788 1.5mg/kg, administered by intravenous infusion every 3 weeks. Primary endpoint was independent review committee (IRC)-assessed confirmed objective response rate (cORR) per RECIST 1.1 in all patients. Results: Between February 9, 2022 and April 30, 2024, totally 138 patients were enrolled and received ARX788 at lease one dose. At baseline there were 8.8% (12/138) of patients with brain metastasis and 76.8% (106/138) with visceral metastasis. The median prior lines of therapy in the metastatic setting were 3 (1, 9). In the intent-to-treat population, IRC-assessed cORR was 44.9% (95%CI: 36.5- 53.6) with a complete response (CR) seen in 3 patients and partial responses (PR) in 59 patients. cORR assessed by investigators was 42.0% (95%CI: 33.7-50.7) with 3 patients of CR and 55 patients of PR. With the median follow-up time of 14.78 months, the IRC-assessed progression-free survival (PFS) was 5.68 months (95%CI: 5.49-8.25), while investigators-assessed PFS was 6.90 months (95%CI: 5.45-7.89). The median duration of response was 13.86 months (95%CI: 6.87-NR). The median OS was not reached and 1-year OS rate was 81.3%. The incidence of treatment-emergent adverse events of any grade occurred in 99.3% (137/138) patients. The most common treatment-related adverse events (>30%) were aspartate aminotransferase increased (65.9%), dry eye (52.9%), alanine aminotransferase increased (44.9%), blurred vision (36.2%), interstitial lung disease (ILD, 35.5%), platelet count decreased (32.6%) and hypokalemia (31.2%). 10.1% of patients had adverse events requiring treatment discontinuation and 27.5% had grade ≥3 adverse events of special interest, mainly containing blurred vision (10.9%), ILD (5.8%), dry eye (7.2%) and keratitis (3.6%). 1 case diagnosed with ILD was reported of treatment-related death. Overall, adverse events were consistent with the known safety profile with low incidence of hematological and gastrointestinal toxicity in the previous studies. Conclusions: ARX788 showed encouraging efficacy and manageable toxicities in patients with HER2-positive advanced breast cancer previously treated with trastuzumab and anti-HER2 TKI. *corresponding author: Zefei Jiang, jiangzf@hotmail.com. Clinical trial information: CTR20213419. Research Sponsor: NovoCodex Biopharmaceuticals Co.,Ltd. Citation Format: Xiaojia Wang, Zefei Jiang, Weimin Xie, Xinshuai Wang, Wei Li, Tao Sun, Xinhong Wu, Yongsheng Wang, Fei Xu, Xiaohua Zeng, Wenyan Chen, Ruizhen Luo, Enfeng Zhao, Min Yan. ACE-Breast-08: a phase I study of ARX788, a novel anti-HER2 antibody-drug conjugate, in patients with TKI pretreated HER2 positive advanced breast cancer [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 PS8-05.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.