Vyloy (zolbetuximab-clzb) / Astellas - LARVOL DELTA

Impact of biomarker-guided targeted therapy on survival in advanced gastric adenocarcinoma: A single-center retrospective analysis (ESMO-GI 2025) - "Trastuzumab is now standard for HER2-positive tumors, immune checkpoint inhibitors in PD-L1-positive and microsatellite instability-high (MSI-H) cases, and zolbetuximab has shown efficacy in CLDN18.2-positive disease. This study reinforces the importance of performing comprehensive biomarker testing and administering appropriate targeted therapies in pt. with advanced GC in real-world settings. Although the survival difference did not reach statistical significance, likely due to sample size, pt."

Biomarker • IO biomarker • Metastases • Retrospective data • Gastric Adenocarcinoma • Gastric Cancer • Oncology • Solid Tumor • CLDN18 • HER-2 • MSI

New Tool in the Toolbox: Patient Selection for Zolbetuximab in Advanced Treatment-Naïve Gastric/Gastroesophageal Junction Adenocarcinoma. (PubMed, Oncologist) - "The recent FDA approval of zolbetuximab for patients with HER2-negative and Claudin-18 isoform 2 (CLDN18.2)-positive advanced or inoperable GEJ/gastric adenocarcinoma has introduced further complexity into frontline therapy decisions in the absence of direct head-to-head comparisons. Here, we review data from GLOW and SPOTLIGHT trials and discuss key tumor and patient characteristics and propose a therapeutic algorithm to help guide frontline treatment decisions for patients with advanced GEJ and gastric adenocarcinoma in light of the availability of zolbetuximab."

IO biomarker • Journal • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • CLDN18

Synthesis and Preclinical Evaluation of a Novel Radiolabeled Anti-Caudin-18.2 Humanized VHH-Based Recombinant Antibody as Radioimmunotherapy Candidate for Gastric Cancer (SNMMI 2025) - "Compared to Zolbetuximab (150 KDa), the smaller molecular size of hTCE009 (78 KDa) enabled improved tumor penetration and reduced blood toxicity. The radiochemical purity of 177Lu-hTCE009 exceeded 95%. The NUGC4CLDN18.2 cell line exhibited a higher expression of CLDN18.2 compared to the SNU620 cell line and the strong membrane antigen-antibody binding ability of hTCE009, Zolbetuximab, respectively, according to the results of flow cytometry and cell immunofluorescence."

IO biomarker • IO Companion diagnostic • Preclinical • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Oncology • Solid Tumor • CLDN18

Claudin 18.2 as a biomarker for imaging and radioligand therapy of solid tumors (SNMMI 2025) - "Zolbetuximab an FDA-approved monoclonal antibody targeting CLD18.2, has shown efficacy in treatment of GC/GEJ in combination with chemotherapy... Radiolabeling of CLDN18.2mAb achieved with molar activities of 45.3 GBq/µmol for [89Zr]Zr4+ and radiochemical yields (RCY) > 95% and 14.8 MBq/nmol for [177Lu]Lu3+ with RCY ~ 60-70%. Serial PET imaging demonstrated a high tumor uptake of [89Zr]Zr-DFO-CLDN18.2mAb in the mouse models at all three time points (%ID/cc at day 6 = 24.4 ± 7.8 in GSU; 36.6 ± 10.1 in PATU8988S; 16.48 ± 4.7 in HUPT-4), and significantly higher than the mice imaged with [89Zr]Zr-DFO-IgG (%ID/cc at day 6 = 4.8 ± 1.9 in GSU, P = 0.01) (Fig. 1A and B)."

Biomarker • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CLDN18

Practical Management of Zolbetuximab Administration: The Project VYLOY Initiative. (PubMed, Cancers (Basel)) - "Patients without prior gastrectomy had higher nausea and vomiting rates, confirming the stomach's role in mediating toxicity. Our results suggest that proactive management can improve the safety and tolerability of zolbetuximab, especially by reducing infusion-related toxicity in real-world practice."

Journal • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Disorder • Oncology • Solid Tumor • CLDN18

LUCERNA: A Study of Zolbetuximab Together With Pembrolizumab and Chemotherapy in Adults With Gastric Cancer (clinicaltrials.gov) - P3 | N=500 | Recruiting | Sponsor: Astellas Pharma Global Development, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor

NEO-CLAUD: A Phase Ib/II Trial of Neoadjuvant Zolbetuximab Plus Docetaxel, Oxaliplatin and S-1 Chemotherapy in Patients With Locally Advanced Gastric Cancer (clinicaltrials.gov) - P1/2 | N=57 | Recruiting | Sponsor: Asan Medical Center | Not yet recruiting ➔ Recruiting

Enrollment open • Gastric Cancer • Oncology • Solid Tumor

Navigating the clinical challenges of zolbetuximab in patients with claudin positive advanced gastric cancer. (PubMed, Eur J Cancer) - "To ensure the optimal use of zolbetuximab, special attention is required during the first cycle, due to higher risk of infusion-related N/V. We suggest that the optimization of both prophylactic and on-treatment antiemetic strategies is essential to enhance zolbetuximab adherence and maximize clinical outcomes."

Journal • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • B3GAT1 • CLDN18 • HER-2 • PD-L1

Unlocking the potential of zolbetuximab in CLDN18.2-positive gastric cancer: A comprehensive systematic review of clinical efficacy and safety. (ASCO 2025) - "Zolbetuximab significantly improves survival outcomes in CLDN18.2-positive gastric cancer with manageable toxicity. These findings support its use with chemotherapy and highlight the need for further trials to optimize dosing and explore novel combinations."

Clinical • Review • Fatigue • Gastric Cancer • Oncology • Solid Tumor • CLDN18

Artificial intelligence-based prediction of claudin 18.2 expression and immune phenotype to guide treatment decisions in patients with gastric cancer. (ASCO 2025) - "Claudin 18.2 (CLDN18.2) is a clinically relevant target for zolbetuximab-based chemotherapy, typically assessed by immunohistochemistry... The AI model reliably predicted CLDN18.2 expression from H&E slides and exhibited reliable performance. The differential survival outcomes observed in subgroups stratified by AI-predicted CLDN18.2 expression and IP suggest its potential utility in guiding first-line treatment decisions for gastric cancer patients. Hazard ratio (HR) for progression-free survival (PFS) and overall survival (OS).reference: Chemo-only"

Clinical • IO biomarker • Gastric Cancer • Oncology • Solid Tumor • CLDN18

First-line treatment of gastric cancer: Clinical data on zolbetuximab (OeGHO-AHOP 2025) - "Sponsored by Astellas Pharma Ges.m.b.H"

Clinical data • Gastric Cancer • Oncology • Solid Tumor

Zolbetuximab case studies & patient management with interactive discussion and Q&A (OeGHO-AHOP 2025) - "Sponsored by Astellas Pharma Ges.m.b.H"

Case study • Clinical • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Guidelines of Onkopedia: What is new? Esophageal Cancer. (PubMed, Oncol Res Treat) - "In the metastatic setting, the approval for the PD-1 inhibitor tislelizumab was extended to the first-line treatment of both, squamous cell- and adenocarcinoma of the esophagus (TAP score (≥ 5%) and for second line for squamous-cell cancer only (independent of PD-L1 expression). Moreover, for gastroesophageal junction (GEJ) tumors, pembrolizumab is available upon PD-L1 expression (CPS ≥ 1) according to the data of the KEYNOTE-859 trial...First-line chemotherapy is to be combined with zolbetuximab in Claudin 18.2 positive GEJ tumors. For biomarker-negative adenocarcinomas of the esophagus and esophago-gastric junction (GEJ), a modified triplet regimen (TFOX) is a newly presented treatment option. Because of high toxicity rates and yet unclear survival benefit this option is only recommended for docetaxel-naïve patients with high remission pressure."

Clinical guideline • IO biomarker • Journal • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Microsatellite Instability • Oncology • Solid Tumor • Squamous Cell Carcinoma • CLDN18 • HER-2 • MSI • PD-L1

Zolbetuximab-clzb: Targeting Claudin 18.2 in Advanced Gastric and Gastroesophageal Adenocarcinoma. (PubMed, Ann Pharmacother) - "The addition of zolbetuximab to a fluoropyrimidine based chemotherapy regimen in highly expressed CLDN18.2 GC/GEJ tumors is associated with improved survival."

Journal • Review • Esophageal Adenocarcinoma • Esophageal Cancer • Fatigue • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • CLDN18 • HER-2 • PD-L1

Lunit Highlights AI's Role in Advancing Precision Oncology at ASCO 2025 with 12 Studies (PRNewswire) - "A third highlighted study introduced an AI model to predict CLDN18.2 expression in gastric cancer. CLDN18.2 is a therapeutic target for zolbetuximab.....Among patients predicted to be CLDN18.2-negative, those with an 'inflamed' phenotype-marked by high tumor-infiltrating lymphocyte (TIL) density-showed significantly better outcomes when treated with immune checkpoint inhibitor plus chemotherapy compared to chemotherapy alone."

Clinical data • Gastric Cancer

Medium- to long-term results of 1st line Nivolumab in unresectable gastric cancer (IGCC 2025) - "Despite many patients having poor PS and peritoneal metastasis, real-world outcomes were comparable to clinical trials, confirming a durable response. As more options like Zolbetuximab and Pembrolizumab become available for 1st-line treatment, detailed management of drug selection and supportive therapy will be essential to further improving prognosis."

Gastric Cancer • Oncology • Solid Tumor

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Antiemesis, Version 2.2025. (NCCN)

NCCN guideline • Multiple Myeloma • Oncology • Solid Tumor

Modeling and Use of Engineering to Overcome On-Target/Off-Tumor Toxicity of Claudin 18.2-Targeted CAR-T cells in Gastric Cancer (ASGCT 2025) - "Claudin 18.2 (CLDN18) targeted therapies, such as monoclonal antibody, zolbetuximab, and CAR-T cell, Satri-cel (CT041) are expanding access to immunotherapy in gastric cancer, however, high rates of nausea and vomiting were seen...We demonstrate that appropriate modeling of anticipated toxicity and careful examination of binding kinetics is critical to engineering a CAR with an optimal therapeutic window. Disease Focus of Abstract:Cancer Solid Tumors"

CAR T-Cell Therapy • IO biomarker • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Graft versus Host Disease • Immunology • Oncology • Solid Tumor • CLDN18

Biomarker-Driven Approach to the Treatment of Metastatic Gastric or Gastroesophageal Adenocarcinoma. (PubMed, J Natl Compr Canc Netw) - "Following the pivotal ToGA trial and the approval of trastuzumab for HER2-positive disease, the search for biomarkers has advanced exponentially. Two recent phase III trials have demonstrated survival benefits with the addition of zolbetuximab to frontline chemotherapy. A number of other biomarker-driven clinical trials are in progress, investigating new targeted agents that are expected to further transform the management of gastric or gastroesophageal adenocarcinoma."

Biomarker • IO biomarker • Journal • Review • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Microsatellite Instability • Oncology • Solid Tumor • CLDN18 • HER-2 • MSI • PD-L1

Treatment Selection for Patients with HER2-Negative Metastatic Gastric Cancer Expressing Claudin 18.2 and PD-L1. (PubMed, Cancers (Basel)) - "Combination therapy of chemotherapy and immune checkpoint inhibitors (ICIs)-either nivolumab or pembrolizumab-is a standard first-line therapy for patients with HER2-negative mGCs that are positive for programmed death-ligand 1 (PD-L1) expression, as defined by a combined positive score (CPS). Treatment selection under this condition has become a critical issue. In this review, we discuss the appropriate treatment selection for HER2-negative mGC patients who are double-positive for CLDN 18.2 and PD-L1 based on clinical data and differences in the mechanism of action and safety profile between zolbetuximab and ICI."

IO biomarker • Journal • Review • Gastric Cancer • Oncology • Solid Tumor • CLDN18 • HER-2 • PD-L1

ILUSTRO: A Study of Zolbetuximab (IMAB362) in Adults With Gastric Cancer (clinicaltrials.gov) - P2 | N=143 | Active, not recruiting | Sponsor: Astellas Pharma Global Development, Inc. | Trial primary completion date: Apr 2025 ➔ Jan 2026

Monotherapy • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • CLDN18 • PD-L1

Phase II RAINSPOT: Zolbetuximab-Paclitaxel-Ramucirumab for CLDN18.2 Positive Gastro-esophageal Cancer (clinicaltrials.gov) - P2 | N=100 | Not yet recruiting | Sponsor: Universitaire Ziekenhuizen KU Leuven

New P2 trial • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor

A Study to Observe the Safety of VYLOY (Zolbetuximab) in People in South Korea With Gastric or Gastroesophageal Junction Cancer. (clinicaltrials.gov) - P=N/A | N=377 | Recruiting | Sponsor: Astellas Pharma Korea, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor

Claudin 18.2 Expression in Gastric Tumors and Other Tumor Types With Gastric Epithelium-like Differentiation. (PubMed, In Vivo) - "Overall, claudin 18.2 positivity occurred primarily in a significant proportion of gastric tumors and other tumors with gastric epithelium-like differentiation. Evaluating claudin 18.2 expression in all such tumors can benefit patients by guiding targeted therapy. Additionally, claudin 18.2 immunostaining serves as a lineage marker for gastric origin or gastric-like differentiation."

Journal • Biliary Cancer • Epstein-Barr Virus Infections • Gastric Cancer • Hepatology • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • CLDN18

Zolbetuximab in combination with chemotherapy in HER2-negative and CLDN 18.2-positive locally advanced unresectable or metastatic gastric or esogastric junction adenocarcinomas (PubMed, Bull Cancer) - No abstract available

Journal • Gastric Cancer • Oncology • HER-2