397P - Efficacy and safety of the recombinant humanized anti-HER2 monoclonal antibody-MMAE conjugate RC48-ADC in patients with HER2-positive or HER2-low expressing, locally advanced or metastatic breast cancer: A single-arm phase II study

Background

Current treatment options for HER2-positive (IHC 3+, or IHC 2+/FISH+) metastatic breast cancer (MBC) 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. Here, we report the efficacy and safety of RC48-ADC in patients with MBC.

Methods

Patients with HER2-positive or HER2-low expressing MBC 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). Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety.

Results

76 female MBC patients were enrolled and treated with RC48. 58 patients (76.3%) were HER2-positive and 18 patients (23.7%) were HER2-low expressing. At baseline, 35 patients (46.0%) had liver metastases, 27 patients (35.5%) had brain metastases, and 67 patients (88.1%) had received ≥3 prior chemotherapy regimens. In the overall population, the ORR was 31.6%. The median PFS was 5.7 months. The DCR was 57.9%. In the HER2-positive subgroup, the ORR and mPFS were 34.5% and 6.3 months. In the HER2-low expressing subgroup, the ORR and mPFS were 22.2% and 3.6 months. In addition, the mPFS in the dual drug combination-treated group was longer than that in the single drug treatment group, with mPFS of 7.1 months and 4.6 months, respectively. The most frequently reported adverse events were increased AST (62.4%), increased ALT (61.9%), decreased white blood cell count (42.4%), and fatigue (30.4%), 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 and could be a future direction of ADC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.