Evaluation of Safety of Treatment With Anti–Epidermal Growth Factor Receptor Antibody Drug Conjugate MRG003 in Patients With Advanced Solid Tumors

作者：Miao‐Zhen Qiu, Yang Zhang, Ye Guo, Wei Guo, Weiqi Nian, Wangjun Liao, Zhongyuan Xu, Wenxue Zhang, Hongyun Zhao, Xiaoli Wei, Liqiong Xue, Wenbo Tang, Yunteng Wu, Guoxin Ren, Ling Wang, Jingle Xi, Yongshuai Jin, Hu Li, Chaohong Hu, Rui‐Hua Xu · 发表于：JAMA Oncology · 年份：2022 · DOI：10.1001/jamaoncol.2022.0503 · 被引用次数：74 · 研究领域：HER2/EGFR in Cancer Research、Colorectal Cancer Treatments and Studies、Advanced Breast Cancer Therapies

Importance: The antibody drug conjugate drug MRG003 comprises an anti-epidermal growth factor receptor (EGFR) humanized immunoglobulin G1 monoclonal antibody that is conjugated with monomethyl auristatin E via a valine-citrulline linker. There is currently insufficient evidence of this drug's safety and efficacy. Objective: To evaluate the safety and maximum tolerated dose of MRG003 in a phase 1a study and investigate the preliminary antitumor activity in EGFR-expressing patients in a phase 1b study. Design, Setting, and Participants: This nonrandomized open-label, single-arm, phase 1, multicenter study of solid tumors was divided into 2 parts, phase 1a dose escalation and phase 1b dose expansion. Patients with advanced or metastatic solid tumors who had failed outcomes from or were not able to receive standard treatment were enrolled in phase 1a without EGFR prescreening. Phase 1b recruited EGFR-positive patients with refractory advanced squamous cell carcinomas of the head and neck (SCCHN), nasopharyngeal carcinoma (NPC), and colorectal cancer (CRC). This study was conducted at 7 Chinese centers between April 11, 2018, and March 29, 2021 (data cutoff date). Data analysis took place between April 2021 and June 2021. Interventions: An intravenous dose of 0.1 to 2.5 mg/kg of MRG003 was administered every 3 weeks during phase 1a. During phase 1b, patients were administered the recommended dose identified in phase 1a. Main Outcomes and Measures: The primary end points were dose-...