Astellas Receives Positive CHMP Recommendation for Zolbetuximab Combined with Chemotherapy in Treating Advanced Gastric and Gastroesophageal Junction Cancer
Monday, July 29, 2024
Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura) announced on July 26, 2024, that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended approval for zolbetuximab in the European Union. This first-in-class claudin 18.2 (CLDN18.2)-targeted monoclonal antibody is proposed for use in combination with fluoropyrimidine- and platinum-based chemotherapy. It targets adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are positive for CLDN18.2. If granted approval, zolbetuximab will be the only CLDN18.2-targeted therapy available in the EU.
Gastric cancer is a significant health issue in Europe, ranking as the sixth leading cause of cancer-related deaths, with over 95,000 fatalities in 2022. Due to overlapping symptoms with other common conditions, the disease is often diagnosed at an advanced stage, resulting in a low five-year survival rate of just 26%. This underscores the need for new therapies to improve patient outcomes.
Moitreyee Chatterjee-Kishore, Ph.D., M.B.A., Senior Vice President and Head of Immuno-Oncology Development at Astellas, highlighted the critical need for new treatments in gastric cancer, noting that zolbetuximab could fill a significant gap in current options. The positive CHMP opinion is based on results from the Phase 3 SPOTLIGHT and GLOW clinical trials, which demonstrated zolbetuximab's efficacy and safety in treating CLDN18.2-positive tumors. The presence of CLDN18.2 is defined by at least 75% of tumor cells showing moderate-to-strong membranous staining.
Astellas has partnered with Roche on the VENTANA® CLDN18 (43-14A) RxDx Assay, a diagnostic test to identify patients eligible for zolbetuximab. This test is under review by the relevant authorities.
The EMA's recommendation will be reviewed by the European Commission, which will decide on the approval for all 27 EU member states, as well as Iceland, Liechtenstein, and Norway.
Previously, zolbetuximab received approval in Japan by the Ministry of Health, Labour and Welfare (MHLW) in March 2024, becoming the first CLDN18.2-targeted therapy approved globally.
Zolbetuximab is a monoclonal antibody that specifically targets CLDN18.2, a protein found on cancer cells. Preclinical studies suggest that it can effectively reduce CLDN18.2-positive cells and inhibit tumor growth through various immune mechanisms.
Gastric cancer is one of the leading causes of cancer deaths in Europe. Often diagnosed at advanced stages due to symptom overlap with other common conditions, early signs include indigestion, abdominal pain, nausea, and bloating. Risk factors include age, gender, family history, H. pylori infection, smoking, and gastroesophageal reflux disease (GERD).
The SPOTLIGHT trial is a global, multi-center, randomized study comparing zolbetuximab plus mFOLFOX6 (a chemotherapy regimen) with placebo plus mFOLFOX6 in patients with CLDN18.2-positive HER2-negative gastric or GEJ adenocarcinoma. The main goal is to evaluate progression-free survival, with secondary goals including overall survival, response rate, duration of response, safety, and quality of life.
The GLOW trial similarly assesses zolbetuximab but uses the CAPOX chemotherapy regimen. It aims to determine zolbetuximab's efficacy and safety in treating the same patient population. The primary focus is on progression-free survival, with secondary endpoints aligned with those of the SPOTLIGHT trial.
A Phase 2 trial is evaluating zolbetuximab in combination with gemcitabine and nab-paclitaxel for metastatic pancreatic adenocarcinoma. Additionally, ASP2138, a bispecific antibody targeting CD3 and CLDN18.2, is in a Phase 1/1b study for similar cancer indications.
Source: astellas.com
