PMID- 35511148 OWN - NLM STAT- MEDLINE DCOM- 20220725 LR - 20220809 IS - 2374-2445 (Electronic) IS - 2374-2437 (Print) IS - 2374-2437 (Linking) VI - 8 IP - 7 DP - 2022 Jul 1 TI - Evaluation of Safety of Treatment With Anti-Epidermal Growth Factor Receptor Antibody Drug Conjugate MRG003 in Patients With Advanced Solid Tumors: A Phase 1 Nonrandomized Clinical Trial. PG - 1042-1046 LID - 10.1001/jamaoncol.2022.0503 [doi] AB - 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-limiting toxic effects in phase 1a and objective response rate in phase 1b. The safety, tolerability, immunogenicity, and pharmacokinetics of MRG003 were assessed. Tumor assessment was evaluated by RECIST 1.1. RESULTS: Twenty-two patients (mean [range] age, 54.5 [32.0-67.0] years; 9 women [41%]) were enrolled in phase 1a and 39 patients (mean [range] age, 50.4 [27.0-75.0] years; 8 women [21%]) in phase 1b. The recommended dose was identified as 2.5 mg/kg. Eighty-nine percent of adverse events (AEs) were associated with MRG003 treatment, and most AEs were grade 1 to 2. Nineteen patients (31%) reported grade 3 or greater treatment-related AEs, including hyponatremia, leukocytopenia, neutropenia, increased aspartate aminotransferase levels, and febrile neutropenia. In phase 1a, 1 patient (5%) achieved a partial response, and 5 (23%) achieved stable disease. In phase 1b, 8 patients (21%) achieved a confirmed partial response, and 12 (31%) achieved stable disease. The objective response rates for SCCHN, NPC, and CRC were 40%, 44%, and 0%, and the disease control rates were 100%, 89%, and 25%, respectively. CONCLUSIONS AND RELEVANCE: The findings of this nonrandomized clinical trial suggest that MRG003 showed a manageable safety profile and promising antitumor activity in patients with EGFR-positive NPC and SCCHN. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT04868344. FAU - Qiu, Miao-Zhen AU - Qiu MZ AD - Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China. FAU - Zhang, Yang AU - Zhang Y AD - Department of Clinical Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China. FAU - Guo, Ye AU - Guo Y AD - Department of Oncology, Shanghai East Hospital Tongji University School of Medicine, Shanghai, China. FAU - Guo, Wei AU - Guo W AD - Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Nian, Weiqi AU - Nian W AD - Chongqing Cancer Institute, Chongqing University Cancer Hospital, Chongqing, China. FAU - Liao, Wangjun AU - Liao W AD - Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China. FAU - Xu, Zhongyuan AU - Xu Z AD - Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China. FAU - Zhang, Wenxue AU - Zhang W AD - Radiation Oncology Department, Tianjin Medical University General Hospital, Tianjin, Tianjin, China. FAU - Zhao, Hong-Yun AU - Zhao HY AD - Department of Clinical Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China. FAU - Wei, Xiaoli AU - Wei X AD - Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China. FAU - Xue, Liqiong AU - Xue L AD - Department of Oncology, Shanghai East Hospital Tongji University School of Medicine, Shanghai, China. FAU - Tang, Wenbo AU - Tang W AD - Department of Oncology, Shanghai East Hospital Tongji University School of Medicine, Shanghai, China. FAU - Wu, Yunteng AU - Wu Y AD - Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Ren, Guoxin AU - Ren G AD - Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Wang, Ling AU - Wang L AD - Chongqing Cancer Institute, Chongqing University Cancer Hospital, Chongqing, China. FAU - Xi, Jingle AU - Xi J AD - Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China. FAU - Jin, Yongshuai AU - Jin Y AD - Lepu Biopharma Co, Beijing, China. FAU - Li, Hu AU - Li H AD - Shanghai Miracogen Inc, Shanghai, China. FAU - Hu, Chaohong AU - Hu C AD - Shanghai Miracogen Inc, Shanghai, China. FAU - Xu, Rui-Hua AU - Xu RH AD - Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China. AD - Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, People's Republic of China. LA - eng SI - ClinicalTrials.gov/NCT04868344 PT - Clinical Trial, Phase I PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA Oncol JT - JAMA oncology JID - 101652861 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Immunoconjugates) RN - 0 (Receptors, Growth Factor) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - *Antibodies, Monoclonal, Humanized/adverse effects MH - ErbB Receptors MH - Female MH - Humans MH - *Immunoconjugates/adverse effects MH - Middle Aged MH - *Neoplasms/drug therapy MH - Receptors, Growth Factor PMC - PMC9073657 COIS- Conflict of Interest Disclosures: Dr Hu reported grants from Lepu Biopharma during the conduct of the study and partial ownership in Lepu Biopharma outside the submitted work as well as patents for US10792370B2 and CN106999606B issued. No other disclosures were reported. EDAT- 2022/05/06 06:00 MHDA- 2022/07/26 06:00 PMCR- 2022/05/05 CRDT- 2022/05/05 11:33 PHST- 2022/05/06 06:00 [pubmed] PHST- 2022/07/26 06:00 [medline] PHST- 2022/05/05 11:33 [entrez] PHST- 2022/05/05 00:00 [pmc-release] AID - 2792015 [pii] AID - cbr220006 [pii] AID - 10.1001/jamaoncol.2022.0503 [doi] PST - ppublish SO - JAMA Oncol. 2022 Jul 1;8(7):1042-1046. doi: 10.1001/jamaoncol.2022.0503.