▎WuXi AppTec Content Team Report

Today (December 31), the official website of the National Medical Products Administration (NMPA) of China announced the latest information,Astellas Pharma, Inc.Zolotuximab for InjectionThe marketing application has been approved.According to an earlier press release from Astellas, this is aAnti-Claudin 18.2 (CLDN18.2) Antibody, this approval is for use in：Combined chemotherapy with fluorouracil and platinum drugs for first-line treatment of patients with CLDN18.2-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Screenshot source: NMPAOfficial Website

According to literature reports[3]，Globally, 952,000 new cases of gastric cancer are reported each year, including 691,000 cases of distal gastric adenocarcinoma (GA) and 260,000 cases of gastroesophageal junction adenocarcinoma (GEJA).GA/GEJA is often not detected early, with about 70% of patients already presenting with locally advanced or late-stage unresectable disease upon diagnosis.(Mainly HER2-negative, locally advanced unresectable or metastatic GA/GEJA), for whom there remains a significant unmet clinical treatment need.

CLDN18.2It is an important protein in the tight junctions of normal tissues and is highly expressed in gastrointestinal cancers, including gastric cancer. Therefore, it is expected to become an effective target for the treatment of solid tumors such as gastric cancer and pancreatic cancer.

Zolbetuximab is a targetedCLDN18.2IgG1 Monoclonal Antibody[3], which specifically binds to CLDN18.2 on the surface of tumor cells to exert its anti-tumor effect.Preclinical studies have shown that this binding effectBy activating two different immune system pathways——Antibody-Dependent Cellular Cytotoxicity (ADCC) and Complement-Dependent Cytotoxicity (CDC) induce cancer cell death, with the aim of achieving tumor treatment.

In August 2023, Astellas announced that the marketing application for Zolbetuximab had been accepted by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration, which is the indication approved this time.The marketing application submitted in China this time isBased on the results of the Phase 3 SPOTLIGHT trial and GLOW trial, both trials are for first-line treatment of CLDN18.2-positive, HER2-negative locally advanced unresectable or metastaticPatients with GEJ adenocarcinoma。Among them, the SPOTLIGHT trial evaluatedZolotuximabThe therapeutic effect of mFOLFOX6 (a combination therapy regimen including oxaliplatin, leucovorin calcium, and fluorouracil) compared with placebo combined with mFOLFOX6;The GLOW trial evaluatedZolotuximabThe therapeutic effect of combining CAPOX (a combination chemotherapy regimen including capecitabine and oxaliplatin) with placebo compared to CAPOX alone.

August 2023, GLOW TrialResults of the interim analysisFull-text publicationIn the authoritative medical journal "Nature Medicine" (Nature Medicine) magazine.The corresponding author of the article isProfessor Ruihua Xu, President of the Sun Yat-sen University Cancer Center and Global Chief Investigator of the GLOW study.The analysis results show that, as of October 7, 2022,Zoltezumab+CAPOX group and placebo +CAPOX group patientsProgression-Free Survival (PFS)The median follow-up times were 12.62 months and 12.09 months, respectively;Overall Survival (OS)The median follow-up times were 17.71 months and 18.43 months, respectively. In the intention-to-treat (ITT) population, both the primary endpoint and key secondary endpoints achieved positive results with statistically and clinically significant importance.

According to Astellas previouslyPublicationTheSPOTLIGHT TrialAs a result, compared with patients receiving placebo plus mFOLFOX6 chemotherapy regimen, patients receivingZolotuximabPatients treated with the mFOLFOX6 chemotherapy regimenProgression-Free Survival (PFS) and Overall Survival (OS) Showed Statistically Significant Improvement. Compared with the placebo group,The risk of disease progression and death in the trial group was significantly reduced by 24.9%, achieving the primary endpoint of the trial.. AcceptZolimomabPatients receiving combination therapyThe median progression-free survival was 10.61 months (vs 8.67 months),Overall survival was also extended,Median overall survival was 18.23 months (vs 15.54 months)The incidence rates of severe treatment-related adverse reactions were similar between the two groups, at 44.8% and 43.5%, respectively, consistent with previous trial results.

References:

[1] NMPA Approves the Marketing of Zolbetuximab Injection. From https://www.nmpa.gov.cn/zhuanti/cxylqx/cxypxx/20241231171015164.html

[2]China's National Medical Products Administration Accepts Astellas' Zolbetuximab Biologics License Application. Retrieved Aug 1，2023, from https://mp.weixin.qq.com/s/K2ufHtGKP5YeNDYarg7Kcw

[3] Shah, M.A., Shitara, K., Ajani, J.A. et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med (2023). https://doi.org/10.1038/s41591-023-02465-7