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Abstract Background: Current treatment options for HER2-positive (IHC 3+, or IHC 2+/FISH+) advanced or metastatic breast cancer at third-line and above have shown limited clinical benefit. There is no recommended HER2-targeting treatment for HER2-low expressing (IHC 2+/FISH-, or IHC 1+) population. RC48 (Disitamab vedotin), a newly developed antibody-drug conjugate (ADC), is comprised of three well-defined components: hertuzumab against the prominent tumor target-HER2, monomethyl auristatin E (MMAE) and a cleavable linker, with a bystanding effect in tumor cell killing. There is a lack of data on the administration of RC48 in the Chinese population. Here, we report the efficacy and safety of RC48-ADC in the advanced or metastatic breast cancer. Methods: Patients with HER2-positive or HER2-low expressing, locally advanced or metastatic breast cancer were eligible and received RC48 2.5 mg/kg every two weeks alone or combined with drugs with different anti-tumor mechanisms, such as immune checkpoint inhibitors (ICIs), tyrosine kinase inhibitors (TKIs) and antiangiogenic compounds. The primary endpoint was the objective response rate (ORR) assessed by the primary researcher. Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), time to progression, and safety. Results: At the time of data cutoff (June 30, 2023), 120 chinese female breast cancer patients were enrolled and treated with RC48-ADC. 82 patients (68.3%) were HER2-positive and 38 patients (31.7%) were HER2-low expressing. At baseline, 52 patients (43.3%) had liver metastases, 40 patients (33.3%) had brain metastases, 70 patients (58.3%) had ≥3 metastases lesions, and 84 patients (70.0%) had received ≥3 prior chemotherapy regimens. In the overall population, the ORR was 38.3% (95% confidence interval CI: 30.0%-47.3%). The median PFS was 5.7 months (95% CI: 4.6-6.9 months). The DCR was 64.2% (95% CI: 54.9%-72.6%). In the HER2-positive subgroup, the ORR and mPFS were 42.7% (95% CI: 32.0%-54.1%) and 6.3 months (95% CI: 4.9-7.6 months). In the HER2-low expressing subgroup, the ORR and mPFS were 29.0% (95% CI: 16.0%-46.1%) and 3.6 months (95% CI: 2.0-5.3 months). In addition, the mPFS in the dual drug combination-treated group were longer than those in the single drug treatment group, with mPFS of 7.1 months (95% CI: 5.0-9.2 months) and 4.6 months (95% CI: 3.5-5.8 months), respectively. The most frequently reported treatment-related adverse events (TRAEs) were increased AST (45.8%), increased ALT (41.7%), decreased white blood cell count (25.0%), and fatigue (25%), most were grade 1-2 in severity. Conclusions: RC48-ADC showed consistent efficacy in HER2-positive and HER2-low expressing subgroups. No new safety signals were observed. Coadministration with ICIs, TKIs and antiangiogenic compounds demonstrated substantially enhanced efficacy compared to the monotherapies and could be a future direction in development of ADC. Citation Format: Fei Qu, Wei Li, Yongmei Yin, Qian Liu. Efficacy and safety of the recombinant humanized anti-HER2 monoclonal antibody-MMAE conjugate RC48-ADC in patients with HER2-positive or HER2-low expressing, metastatic breast cancer: a single-arm phase II study abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-04-05.
Qu et al. (Thu,) studied this question.