Abstract P5-05-07: A prospective, multicenter, single-arm clinical study of inetetamab combined with pyrotinib and capecitabine/vinorelbine in the treatment of HER2-positive metastatic breast cancer resistant to previous trastuzumab treatment

Abstract Background: Inetetamab is an innovative Fc-modified monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2). Pyrotinib is a tyrosine kinase inhibitor (TKI). Theoretically, the combination of a large-molecule monoclonal antibody and a small-molecule TKI can exert a better antitumor effect. In the study, inetetamab in combination with pyrotinib and capecitabine/vinorelbine was used to treat HER2-positive metastatic breast cancer (MBC) that was previously resistant to trastuzumab. This study evaluated the efficacy and safety of the treatment regimen and conducted an exploratory analysis of the clinicopathological characteristics of the benefiting population. Methods: The prospective, multicenter study enrolled 40 patients with HER2-positive MBC who received inetetamab in combination with pyrotinib and capecitabine/vinorelbine between December 2020 and December 2023. All enrolled patients were previously resistant to trastuzumab treatment. The primary endpoint was progression-free survival (PFS) estimated using the Kaplan-Meier method. The secondary endpoints were objective response rate (ORR), disease control rate (DCR), and safety. Results: Among all patients receiving treatment, the median number of treatment lines was 3, and the median PFS was 8.2 months (95% CI 2.860-13.540). The correlation between different clinicopathological characteristics and mPFS was assessed using the Kaplan-Meier method. The results showed that significant associations with mPFS were observed for estrogen receptor (HR) positivity (P = 0.019), disease-free survival (DFS) > 24 months (P = 0.005), absence of lung metastasis (P = 0.017), Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2 (P < 0.001), ≤3 lines of inetetamab treatment (P < 0.001), secondary resistance to trastuzumab (P = 0.011), no prior TKI treatment (P < 0.001), no prior antibody-drug conjugate (ADC) treatment (P < 0.001), and no prior cranial radiotherapy (P = 0.026). Multivariate analysis using the Cox model revealed that the independent prognostic factors affecting mPFS were no prior TKI treatment (HR = 0.260, 95% CI 0.079-0.859, P = 0.027) and ≤3 lines of inetetamab treatment (HR = 0.128, 95% CI 0.025-0.654, P = 0.014). In this study, the ORR was 62.5%, and the DCR was 77.5%. The Fisher's exact test was used to examine the correlation between different clinicopathological characteristics and ORR. The results suggested significant associations with ORR for DFS > 24 months (P < 0.001), ECOG performance status score of 0-2 (P = 0.009), ≤3 lines of inetetamab treatment (P < 0.001), secondary resistance to trastuzumab (P = 0.021), no prior TKI treatment (P = 0.003), no prior ADC treatment (P = 0.008), and no prior cranial radiotherapy (P = 0.018). The most common adverse reactions of all grades in this study were diarrhea (95.0%), leukopenia (45.0%), neutropenia (42.5%), anemia (37.5%), fatigue (40.0%), increased aspartate aminotransferase (AST) (37.5%), increased alanine aminotransferase (ALT) (35.0%), and nausea (30.0%). The incidence of severe adverse reactions of grade 3 or above was relatively low (all < 20%). Conclusion: The combination of inetetamab with pyrotinib and capecitabine/vinorelbine can serve as a good treatment option for HER2-positive MBC that is resistant to trastuzumab. In particular, patients who have not received TKI treatment before and have ≤3 lines of inetetamab treatment can experience more significant benefits in terms of PFS. All adverse events (AEs) are controllable and tolerable. Clinical trial information: ChiCTR2300074366. Research Sponsor: None. Citation Format: Yan Xue, Junmei Zhang, Xuezheng Wang, Donghui Li, Dongmei Jiang, Yefa Gao, Xingyan Li. A prospective, multicenter, single-arm clinical study of inetetamab combined with pyrotinib and capecitabine/vinorelbine in the treatment of HER2-positive metastatic breast cancer resistant to previous trastuzumab treatment [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 P5-05-07.