939P - Efficacy and safety of a novel anti-EGFR ADC MRG003 in recurrent or metastatic squamous cell carcinoma of the head and neck patients

Background

Patients (pts) with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) who failed platinum and/or immune check-point inhibitor have a poor prognosis with OS～6 moths. Epidermal growth factor receptor (EGFR) is aberrantly over-expressed in R/M SCCHN pts with high frequency. MRG003 is a novel ADC composed of a humanized anti-EGFR mAb conjugated to MMAE via a vc-linker. This study was designed to evaluate the efficacy and safety of MRG003 in R/M SCCHN.

Methods

Histologically or cytologically confirmed R/M SCCHN (including oral cavity, oropharynx, hypopharynx, and larynx) pts were divided into two groups of MRG003 (2.0 or 2.3 mg/kg, Q3W). Eligible pts were aged 18-75 years old and had progressed at least one line of standard therapy. The primary endpoint was the objective response rate (ORR). The secondary endpoints included disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), and safety.

Results

Sixty-seven pts in total were enrolled with 35 pts received 2.0 mg/kg of MRG003, and 32 pts received 2.3 mg/kg. The median age was 54 (26-75) years, and 91% of pts’ ECOG performance status was 1. The immunohistochemistry detection of EGFR expression was performed in 65 pts, and 62 pts (95.4%) were EGFR-positive. The median line of prior therapy was 2 (1-5). Most pts had received prior platinum (95.6%), PD-1/L1 inhibitor (76.1%), cetuximab (47.8%). At the data cutoff, the ORR was 30.6% in all EGFR-positive pts. In the 2.3 mg/kg dose group, the ORR and DCR was 43% and 86% in 2/3-line pts who had failed prior platinum and PD-1/L1 inhibitor, and the mPFS and mOS were 4.2 months and 11.3 months, respectively. The common treatment-related adverse events (TRAEs) included constipation (25.8%), pruritus (24.2%), and anemia (22.6%). Common grade 3 or above TRAEs included white blood cell count decreased (6.5%), anemia (4.8%).

Conclusions

MRG003 was well tolerated with a manageable safety profile, and showed promising efficacy in 2/3-line R/M SCCHN pts who failed prior platinum and PD-1/L1inhibitor. A phase III study is currently ongoing to further explore the efficacy of MRG003 in compared with cetuximab/methotrexate in this setting.

Clinical trial identification

NCT04868162 First Posted: April 30, 2021.

Editorial acknowledgement

Legal entity responsible for the study

Shanghai Miracogen Inc.

Funding

Shanghai Miracogen Inc.

Disclosure

All authors have declared no conflicts of interest.