Conference Correspondent

Comparison of ARX788 and Lapatinib/Capecitabine in Patients with HER2-Positive Locally Advanced or Metastatic Breast Cancer

Conference Correspondent 

A novel antibody–drug conjugate that consists of a human epidermal growth factor receptor 2 (HER2)-targeting monoclonal antibody site-specifically conjugated with payload AS269 (Amberstatin), a highly potent tubulin inhibitor, is currently being investigated.

In heavily pretreated patients who had received a median of 5 previous treatment regimens and had HER2-positive metastatic breast cancer, promising results were shown from a phase 1 study, in cohorts dosing from 1.1 mg/kg to 1.5 mg/kg antitumor activity was shown with an objective response rate of 52.0%.

Among the patients who had received tyrosine kinase inhibitor treatment previously, the objective response rate was 48.5%. In the 1.5-mg/kg every-3-weeks cohort, the objective response rate was 68.4% and the median progression-free survival was not reached; this was because the majority of subjects were still receiving ARX788 treatment.

Xichun Hu, MD, PhD, Professor, Medical Oncology, Shanghai Cancer Center, Fudan University Shanghai Cancer Center, China, and colleagues provided an overview of a phase 2/3 study evaluating patients with HER2-positive advanced breast cancer the safety and efficacy of ARX788 compared with lapatinib (Tykerb) and capecitabine (Xeloda).

ZMC-ARX788-211 is a phase 2/3 randomized, multicenter, open-label trial comparing ARX788 with lapatinib and capecitabine in patients with HER2-positive locally advanced or metastatic breast cancer. From 45 centers in China, approximately 440 patients will be randomized 1:1 to receive ARX788 1.5 mg/kg every 3 weeks or lapatinib plus capecitabine until disease progression, intolerable toxicity, or death. All patients included in the study require progression on ≥1 previous lines of HER2 therapy. Progression-free survival will be the primary outcome measure. Investigator-assessed progression-free survival, duration of response, overall survival, safety, immunogenicity, objective response rate, disease control rate, and population pharmacokinetics are considered secondary outcome measures. Two interim analyses will be included in the study.

When 160 patients have completed cycle 4 assessment to detect potential early futility trends, the first interim analysis will be completed. An international phase 2/3 trial of ARX788 is currently being planned.

Source: Hu X, Zhang J, Wang L, et al. A randomized, multicenter, open-label phase II/III study of ARX788 vs Lapatinib and Capecitabine in patients with HER2-positive locally advanced or metastatic breast cancer (ZMC-ARX788-211). Presented at: San Antonio Breast Cancer Symposium, December 8-11, 2020. Abstract PS10-57.

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