Astellas Pharma Announces FDA Approval for VYLOY in Gastric Cancer Treatment
Astellas Pharma has announced that the U.S. Food and Drug Administration (FDA) has granted approval for VYLOY (zolbetuximab-clzb) in combination with fluoropyrimidine- and platinum-based chemotherapy as a first-line treatment for adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma, specifically for patients whose tumors are CLDN 18.2 positive, as determined by an FDA-approved test.
VYLOY is the first and only therapy targeting CLDN 18.2 to receive approval in the United States.
In the SPOTLIGHT and GLOW clinical trials, approximately 38% of patients screened had tumors that tested positive for CLDN 18.2. This positivity is defined as ≥75% of tumor cells showing moderate to strong membranous CLDN 18 immunohistochemical staining, as evaluated by Roche’s VENTANA CLDN18 (43-14A) RxDx Assay. Astellas collaborated with Roche on the newly approved immunohistochemistry (IHC) companion diagnostic test to identify potential candidates for VYLOY.
Moitreyee Chatterjee-Kishore, Ph.D., M.B.A., Senior Vice President and Head of Immuno-Oncology Development at Astellas, stated, “The approval of VYLOY as the first targeted therapy for CLDN 18.2-positive patients in the U.S. underscores our commitment to advancing science for serious diseases like gastric and GEJ cancers, which are often diagnosed at advanced stages. This milestone is a result of years of focused research on a novel biomarker, and we appreciate the contributions of patients, investigators, and Astellas team members who made this progress possible.”
Samuel J. Klempner, M.D., Associate Professor at Harvard Medical School and Medical Oncologist at Massachusetts General Hospital, remarked, “Despite recent advancements in treating locally advanced unresectable and metastatic gastric and GEJ cancers, there remains a significant unmet need among patients. The approval of VYLOY, grounded in the pivotal Phase 3 SPOTLIGHT and GLOW trials, introduces a novel biomarker and a new treatment option for CLDN 18.2 positive patients, aiding those involved in treatment decision-making.”
The approval is based on findings from the Phase 3 SPOTLIGHT and GLOW clinical trials. The SPOTLIGHT study assessed VYLOY combined with mFOLFOX6 (a chemotherapy regimen including oxaliplatin, leucovorin, and fluorouracil) against a placebo plus mFOLFOX6. The GLOW study compared VYLOY with CAPOX (a combination of capecitabine and oxaliplatin) to a placebo plus CAPOX. Both trials successfully met their primary endpoint of progression-free survival (PFS) and a key secondary endpoint of overall survival (OS) for patients treated with VYLOY plus chemotherapy versus those receiving placebo plus chemotherapy. The most frequently reported all-grade treatment-emergent adverse events (TEAEs) in the VYLOY groups included nausea, vomiting, and decreased appetite.
An FDA-approved test is utilized to identify patients eligible for VYLOY. The VENTANA CLDN18 (43-14A) RxDx Assay from Roche is an FDA-approved IHC test for determining CLDN 18.2 status. Testing is currently available at multiple reference laboratories across the U.S. and is expected to expand to additional laboratories over time. For information on where to test for CLDN 18.2 status, please visit VYLOYhcp.com.*
With today’s FDA decision, VYLOY is now approved in five global markets: Japan, the United Kingdom, the European Union, South Korea, and the U.S. Japan’s Ministry of Health, Labour and Welfare was the first to approve VYLOY on March 26, 2024. In August, it received approval from the UK Medicines and Healthcare products Regulatory Agency, followed by marketing authorization from the European Commission in September, and approval from the Ministry of Food and Drug Safety in South Korea. Astellas is actively pursuing additional applications for VYLOY in regulatory agencies worldwide.
Astellas has factored the impact of this approval into its financial forecast for the current fiscal year, ending March 31, 2025.
Please note that VYLOYhcp.com is currently being launched; if you are unable to access the site immediately, please try again later.
About VYLOY™ (zolbetuximab-clzb)
VYLOY™ (zolbetuximab-clzb) is a claudin 18.2-directed cytolytic antibody approved by the FDA in conjunction with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are CLDN 18.2 positive, as determined by an FDA-approved test. As a first-in-class monoclonal antibody, VYLOY targets and binds to CLDN 18.2, a transmembrane protein, and induces cell depletion via antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).
VYLOY (zolbetuximab-clzb) U.S. Indication & Important Safety Information
INDICATION
VYLOY, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are CLDN 18.2 positive, as determined by an FDA-approved test.
IMPORTANT SAFETY INFORMATION
Warnings and Precautions
Hypersensitivity reactions, including severe anaphylactic reactions and serious infusion-related reactions (IRRs), have been reported in clinical studies involving VYLOY. Any grade of hypersensitivity reactions, including anaphylactic reactions, was observed in 18% of patients receiving VYLOY in combination with mFOLFOX6 or CAPOX. Severe (Grade 3 or 4) hypersensitivity reactions occurred in 2% of patients, with seven patients (1.3%) permanently discontinuing VYLOY due to hypersensitivity reactions, including two patients (0.4%) due to anaphylaxis. A total of 17 (3.2%) patients required dose interruptions, while three patients (0.6%) required infusion rate reductions due to hypersensitivity reactions. All-grade IRRs were observed in 3.2% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX. Severe (Grade 3) IRRs were noted in two patients (0.4%) receiving VYLOY. An IRR led to permanent discontinuation in two patients (0.4%) and dose interruption in seven (1.3%). The infusion rate was reduced for two (0.4%) patients due to an IRR. It is essential to monitor patients during and for two hours after VYLOY infusion for hypersensitivity reactions indicative of anaphylaxis (such as urticaria, repetitive cough, wheezing, throat tightness, or voice changes).
Severe Nausea and Vomiting: VYLOY is emetogenic, with nausea and vomiting occurring more frequently during the first treatment cycle. Overall, nausea and vomiting were reported in 82% and 67% of patients treated with VYLOY plus mFOLFOX6, and in 69% and 66% of patients treated with CAPOX, respectively. Severe (Grade 3) nausea occurred in 16% and 9% of patients, while severe (Grade 3) vomiting occurred in 16% and 12% of patients in combination with mFOLFOX6 or CAPOX, respectively. Nausea led to permanent discontinuation of VYLOY in 18 (3.4%) patients and dose interruptions in 147 (28%). Vomiting caused permanent discontinuation in 20 (3.8%) patients and dose interruptions in 150 (28%). Patients should be pre-treated with antiemetics prior to each VYLOY infusion, and those experiencing nausea or vomiting should be managed with antiemetics or fluid replacement, with potential interruptions or permanent discontinuation based on severity.
