Japan’s Ministry of Health, Labour and Welfare (MHLW) has approved Astellas Pharma’s  VYLOY™ (zolbetuximab), an anti-claudin 18.2 (CLDN18.2) monoclonal antibody, in combination with chemotherapy, for patients with human epidermal growth factor receptor 2 (HER2)-negative, CLDN18.2 positive, unresectable, advanced or recurrent gastric cancer.
VYLOY is the first and only CLDN18.2-targeted therapy approved by any regulatory agency in the world.
Gastric cancer is frequently diagnosed in the advanced or metastatic stage due to overlapping early-stage symptoms with other more common stomach conditions. Despite efforts to reduce its impact, gastric cancer is the third deadliest cancer in Japan, with 126,724 cases diagnosed in 2022.
Moitreyee Chatterjee-Kishore, Ph.D., M.B.A., Senior Vice President and Head of Immuno-Oncology Development, Astellas, said: “The approval of VYLOY by the MHLW marks a new era in the treatment of gastric cancer, offering the first and only targeted therapy option for CLDN18.2-positive patients living with this devastating disease.
“Astellas is proud to help address the urgent therapeutic need for this hard-to-treat cancer in Japan, where incidence rates are among the highest globally. Importantly, this approval holds the potential to provide eligible patients with more precious time with their loved ones, delivering on our commitment to improve patient outcomes.”
Kohei Shitara, MD, Primary Investigator for the SPOTLIGHT Trial and Head, Department of Gastrointestinal Oncology, the National Cancer Center Hospital East in Kashiwa, Japan, said: “Developing new targeted therapies is critical for diseases like advanced gastric adenocarcinoma, which has had very limited treatment options and is often discovered at an advanced stage.
“As the primary investigator for the Phase 3 SPOTLIGHT clinical trial, I witnessed firsthand the significant improvement in progression-free survival and overall survival for patients treated with VYLOY in combination with chemotherapy compared to those treated with placebo plus chemotherapy. These results support VYLOY as a new treatment option for the CLDN18.2-positive population in Japan, where there were nearly 44,000 deaths caused by gastric cancer in 2022 alone.”
The approval is based on results from the Phase 3 SPOTLIGHT and GLOW clinical trials for first-line treatment in patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors were CLDN18.2 positive.
The SPOTLIGHT study evaluated VYLOY plus mFOLFOX6 (a combination chemotherapy regimen that includes oxaliplatin, leucovorin, and fluorouracil) compared to placebo plus mFOLFOX6. The GLOW study evaluated VYLOY plus CAPOX (a combination chemotherapy regimen that includes capecitabine and oxaliplatin) compared to placebo plus CAPOX.
Both trials met their primary endpoint, progression-free survival (PFS), as well as a key secondary endpoint, overall survival (OS), showing statistical significance in patients treated with VYLOY plus chemotherapy compared to placebo plus chemotherapy.
The most frequent treatment-emergent adverse events (TEAEs) ≥20% for VYLOY in combination with mFOLFOX6 or CAPOX were nausea, vomiting, decreased appetite, neutropenia, and decreased weight. In clinical trials, adverse reactions were managed by antiemetics, dose interruptions, and infusion rate adjustments.
In both SPOTLIGHT and GLOW, approximately 38% of patients screened had tumors that were CLDN18.2 positive. CLDN18.2 positivity is defined as ≥75% of tumor cells showing moderate-to-strong membranous CLDN18 staining, which should be confirmed by a pathologist or laboratory with adequate experience using the approved in-vitro diagnostic agent or medical device.
Astellas collaborated with Roche Diagnostics on the newly approved VENTANA®CLDN18 (43-14A) RxDx Assay, an immunohistochemistry (IHC) companion diagnostic (CDx) test, to identify patients who may be eligible for VYLOY. Testing will be available in Japan at multiple central laboratories and is expected to expand to additional laboratories over time.
Astellas has also submitted applications for VYLOY to regulatory agencies around the world, and review is ongoing.
