2. Academic Validation
  3. Efficacy, safety and genomic analysis of SCT200, an anti-EGFR monoclonal antibody, in patients with fluorouracil, irinotecan and oxaliplatin refractory RAS and BRAF wild-type metastatic colorectal cancer: a phase Ⅱ study

Efficacy, safety and genomic analysis of SCT200, an anti-EGFR monoclonal antibody, in patients with fluorouracil, irinotecan and oxaliplatin refractory RAS and BRAF wild-type metastatic colorectal cancer: a phase Ⅱ study

  • EBioMedicine. 2024 Feb:100:104966. doi: 10.1016/j.ebiom.2024.104966.
Lin Yang 1,  Wen Zhang 1,  Nanfeng Fan 2,  Peiguo Cao 3,  Ying Cheng 4,  Lingjun Zhu 5,  Suxia Luo 6,  Hong Zong 7,  Yuxian Bai 8,  Jianfeng Zhou 9,  Yanhong Deng 10,  Yi Ba 11,  Tianshu Liu 12,  Mayinuer Aili 13,  Xianli Yin 14,  Kangsheng Gu 15,  Guanghai Dai 16,  Jieer Ying 17,  Jianhua Shi 18,  Yajie Gao 19,  Wei Li 20,  Guohua Yu 21,  Liangzhi Xie 22,  Wenlin Gai 22,  Yan Wang 22,  Peng Meng 23,  Yuankai Shi 24
Affiliations

Affiliations

  • 1 Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, China.
  • 2 Department of Abdominal Oncology, Fujian Provincial Cancer Hospital, Fuzhou, China.
  • 3 Department of Oncology, The Third Xiangya Hospital of Central South University, Changsha, China.
  • 4 Department of Oncology, Cancer Hospital of Jilin Province, Changchun, China.
  • 5 Department of Oncology, Jiangsu Province Hospital, Nanjing, China.
  • 6 Department of Medical Oncology, Henan Provincial Cancer Hospital, Zhengzhou, China.
  • 7 Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • 8 Department of Internal Medicine, Harbin Medical University Cancer Hospital, Harbin, China.
  • 9 Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
  • 10 Department of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
  • 11 Department of Gastroenterology, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China.
  • 12 Department of Medical Oncology, Zhongshan Hospital Affiliated to Fudan University, Shanghai, China.
  • 13 The Third Department of Oncology, Cancer Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
  • 14 Department of Gastroenterology, Hunan Cancer Hospital, Changsha, China.
  • 15 Department of Medical Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
  • 16 Department of Medical Oncology, Chinese PLA General Hospital, Beijing, China.
  • 17 Department of Abdominal Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
  • 18 Department of Medical Oncology, Linyi Cancer Hospital, Linyi, China.
  • 19 Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
  • 20 Cancer Center, The First Hospital of Jilin University, Changchun, China.
  • 21 Department of Oncology, Weifang People's Hospital, Weifang, China.
  • 22 Beijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing, China.
  • 23 Burning Rock Biotech, Shanghai, China.
  • 24 Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, China. Electronic address: syuankai@cicams.ac.cn.
PMID: 38217945 DOI: 10.1016/j.ebiom.2024.104966
Abstract

Background: Limited therapeutic options are available for metastatic colorectal Cancer (mCRC) patients after failure of first- and second-line therapies, representing an unmet medical need for novel therapies.

Methods: This is an open-label, single arm, multicenter, phase Ⅱ study aiming to perform the efficacy, safety and genomic analysis of SCT200, a noval fully humanized IgG1 anti-epidermal growth factor receptor (EGFR) monoclonal antibody, in patients with fluorouracil, irinotecan and oxaliplatin refractory Ras and BRAF wild-type mCRC. SCT200 (6 mg/kg) was given weekly for the first six weeks, followed by a higher dose of 8 mg/kg every two weeks until disease progression or unacceptable toxicity. Primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR) and secondary endpoints included ORR in patients with left-sided tumor, disease control rate (DCR), duration of response (DoR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and safety.

Findings: From February 12, 2018 to December 1, 2019, a total of 110 patients aged between 26 and 77 years (median: 55; interquartile range [IQR]: 47-63) with fluorouracil, oxaliplatin, and irinotecan refractory Ras and BRAF wild-type mCRC were enrolled from 22 hospitals in China. As the data cut-off date on May 15, 2020, the IRC-assessed ORR and DCR was 31% (34/110, 95% confidence interval [CI] 22-40%) and 75% (82/110, 95% CI 65-82%), respectively. Thirty one percent (34/110) patients achieved confirmed partial response (PR). The median PFS and median OS were 5.1 months (95% CI 3.4-5.2) and 16.2 months (95% CI 11.1-not available [NA]), respectively. The most common ≥ grade 3 treatment-related adverse events (TRAEs) were hypomagnesemia (17%, 19/110) and acneiform dermatitis (11%, 12/110). No deaths occurred. Genomic analysis suggested positive association between MYC amplification and patients' response (P = 0.0058). Ras/Raf mutation and MET amplification were the most frequently detected resistance mechanisms. Patients with high circulating tumor DNA (ctDNA) at baseline or without ctDNA clearance at the 7th week after the first dose of SCT200 administration before receiving SCT200 had worse PFS and OS.

Interpretation: SCT200 exhibited promising clinical efficacy and manageable safety profiles in Ras and BRAF wild-type mCRC patients progressed on fluorouracil, irinotecan and oxaliplatin treatment. The baseline ctDNA and ctDNA clearance status at the 7th week after the first dose of SCT200 administration before receiving SCT200 could be a potential prognostic biomarker for Ras and BRAF wild-type mCRC patients with SCT200 therapy.

Funding: This study was sponsored by Sinocelltech Ltd., Beijing, China and partly supported by the National Science and Technology Major Project for Key New Drug Development (2019ZX09732001-006, 2017ZX09304015).

Keywords

Anti-epidermal growth factor receptor; BRAF; Circulating tumor DNA; Metastatic colorectal cancer; Monoclonal antibody; RAS.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-P991507
    Anti-EGFR Antibody