Astellas Announces FDA Acceptance and Priority Review of Zolbetuximab BLA for First-Line Treatment of CLDN18.2-Positive, HER2-Negative Gastric or Gastroesophageal Junction Adenocarcinoma

On July 6, Astellas announced that the Biologics License Application (BLA) for its investigational zolbetuximab has been accepted by the FDA and granted Priority Review designation for the first-line treatment of CLDN18.2-positive, HER2-negative locally advanced unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma.PDUFA Date: January 12, 2024If approved, zolbetuximab will become the first CLDN18.2-targeted drug to be approved for marketing in the United States.

Zolbetuximab is a first-in-class monoclonal antibody targeting CLDN18.2 independently developed by Ganymed, a subsidiary of Astellas. CLDN18.2 is primarily expressed in gastric epithelial cells and is highly expressed in primary malignant tumors such as gastric cancer, breast cancer, colon cancer, and liver cancer. Preclinical studies have shown that zolbetuximab induces cancer cell death by activating two different immune system pathways (antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity).

This BLA is primarily based on the clinical results of two Phase III studies, SPOTLIGHT and GLOW.

SPOTLIGHT Study: Evaluating the Efficacy and Safety of Zolbetuximab Combined with mFOLFOX6 (a Regimen Including Oxaliplatin, Leucovorin, and Fluorouracil) as First-Line Treatment in CLDN18.2-Positive, HER2-Negative Patients with Locally Advanced Unresectable or Metastatic G/GEJ Adenocarcinoma.

Results showed that, compared with the placebo plus mFOLFOX6 group, the combination of zolbetuximab and mFOLFOX6 achieved statistically significant improvements in progression-free survival (PFS) and overall survival (OS). Specifically, compared with the placebo group, the combination of zolbetuximab and mFOLFOX6 reduced the risk of disease progression or death by 24.9%, reaching the primary endpoint of the study. The median PFS was 10.61 months in the treatment group and 8.67 months in the placebo group.

The study also showed that the combination of zolbetuximab and mFOLFOX6 significantly extended OS, reducing the risk of death by 25.0%. The median OS for the treatment group and the placebo group was 18.23 months and 15.54 months, respectively.

The GLOW study compared the efficacy of Zolbetuximab + CAPOX (capecitabine + oxaliplatin) versus placebo + CAPOX in 507 treatment-naïve G/GEJ adenocarcinoma patients with high CLDN18.2 expression (expression level ≥75%).

The results showed that the Zolbetuximab group extended PFS by 1.4 months and OS by 2.2 months. Additionally, the objective response rates (ORR) for the two groups were 53.8% and 48.8%, respectively; the mDOR for the two groups were 6.28 months and 6.18 months, showing no significant difference.

In terms of treatment-emergent serious adverse events (TEAEs), the incidence rates were similar between the two groups, with 47.2% in the zolbetuximab group vs. 49.8% in the placebo group, consistent with previous studies. During the GLOW study, the most common TEAEs in the zolbetuximab group compared to the placebo group were nausea (68.5% vs. 50.2%), vomiting (66.1% vs. 30.9%), and decreased appetite (41.3% vs. 33.7%).

Copyright © 2023 PHARMCUBE. All Rights Reserved.

Welcome to forward, share, and reasonably cite. When citing, please clearly indicate the source of the article; if you need to reprint, please leave a message to the WeChat Official Account or send a message, and include the name and ID of the official account.

Disclaimer: The information in this WeChat article is for general reference only and should not be used directly as decision-making content. PharmaCube assumes no responsibility for any loss incurred by any party due to the use of the content herein.

Exciting Preview

Online Live Streaming & Offline Salon