Research in Context

Research in Context is a structured summary that editors at The Lancet’s journals ask all authors to provide when submitting an original research article. Read more

A collaboration with

CMG901: phase 1 findings in previously treated gastric and gastro-oesophageal junction cancer

An open-label phase 1 study reported objective response and disease-control rates for the investigational CLDN18.2-specific antibody–drug conjugate CMG901, with higher rates in patients with greater CLDN18.2 expression; further trials are ongoing.

  • Dan-Yun Ruan, MD; Fu-Rong Liu, MD; Xiao-Li Wei, MD; Su-Xia Luo, MD; Zhi-Xiang Zhuang, MD; Zhen-Ning Wang, MD; et al.

  • January 6, 2025

  • The Lancet Oncology
  • The Lancet Oncology, Volume 26, Issue 2, Pages 227–238
  • 10.1016/S1470-2045(24)00636-3

Share

Evidence before this study

Advanced gastric or gastro-oesophageal junction cancer is a leading global cause of cancer-related death, with high metastasis rates and poor survival outcomes. We searched PubMed on Aug 10, 2020, for clinical trials by using the terms (“Claudin 18” OR “CLDN18.2”) AND (“trial”), with no language or time restrictions. We identified two articles that reported on outcomes of the claudin-18 isoform 2 (CLDN18.2) monoclonal antibody zolbetuximab monotherapy for gastric or gastro-oesophageal junction adenocarcinoma. The evidence showed that zolbetuximab monotherapy had a favourable safety profile with limited efficacy in patients with gastric and gastro-oesophageal junction cancer with moderate-to-high CLDN18.2 expression in at least 50% of tumour cells (objective response in four [9%] of 43 patients; disease control in ten [23%] of 43 patients). However, of the ten patients reaching disease control, nine (90%) had moderate-to-high CLDN18.2 expression (CLDN18.2 2+ or greater staining intensity during immunohistochemistry) in 70% or more tumour cells.

Added value of this study

This study is, to our knowledge, the first reporting a CLDN18.2-specific antibody–drug conjugate for the treatment of cancer. This open-label, phase 1 trial is the first study investigating the antitumour activity and safety of a CLDN18.2-specific antibody–drug conjugate, CMG901, in patients with previously treated gastric or gastro-oesophageal junction cancer. CMG901 had an objective response rate of 28% and a disease control rate of 63% in gastric or gastro-oesophageal junction cancer. In the subgroup of patients with CLDN18.2 at least 2+ staining intensity in 20% or more tumour cells, the objective response rate was 33% and the disease control rate was 67%. The safety profile of CMG901 was manageable.

Implications of all the available evidence

There are inadequate targeted therapies for gastric or gastro-oesophageal junction cancer. Our findings have shown the potential clinical benefits of CMG901 in patients with advanced gastric or gastro-oesophageal junction cancer. Further global trials of CMG901 as monotherapy in second or later line gastric or gastro-oesophageal junction cancer, and in combination with chemotherapy or immunotherapy in the first-line gastric or gastro-oesophageal junction cancer, are ongoing. If these findings are supported in the subsequent studies, CMG901 could become a new option for the treatment of patients with advanced gastric or gastro-oesophageal junction cancer.

Source: The Lancet Oncology

Your research deserves a global audience

The Lancet Group reaches millions of clinicians and researchers worldwide.

Publish with The Lancet Group

Related Content

Single randomised trial: investigational AI system reduced gastric neoplasm miss rate versus standard endoscopy.

The ENDOANGEL-LD AI system reduced gastric neoplasm miss rates compared with standard upper gastrointestinal endoscopy; the authors describe potential future support for targeted biopsies.

  • by Lianlian Wu, MD; Renduo Shang, MD; Prateek Sharma, MD; Wei Zhou, MD; Jun Liu, MM; Liwen Yao, MD; et al.

  • July 20, 2021

Clinician discussing endoscopy images with a patient.
Phase 3 ASTRUM-006 evaluates biomarker-driven perioperative serplulimab strategy in resectable gastric or GEJ adenocarcinoma

In PD-L1 CPS ≥5 disease, the phase 3 study reported improved event-free survival and pathological complete response with neoadjuvant serplulimab plus chemotherapy followed by adjuvant serplulimab monotherapy versus neoadjuvant and adjuvant chemotherapy.

  • by Lin Shen, MD; Xiaotian Zhang, MD; Ke Ji, MD; Linzhi Lu, MD; Quan Wang, MD; Quanlin Guan, MD; et al.

  • June 1, 2025

Surgical team performing an operation.