Vyloy (zolbetuximab-clzb) / Astellas - LARVOL DELTA

Claudin 18.2 Immunohistochemistry in Gastroesophageal Adenocarcinomas: A Study of Interobserver Variability Among Gastrointestinal Pathologists. (PubMed, Hum Pathol) - "The study demonstrated substantial interobserver agreement among gastrointestinal pathologists in evaluating CLDN18 staining for the purposes of zolbetuximab eligibility. Assessment of weaker staining intensities was a source of greater variability. These findings highlight the need for standardized scoring of CLDN18 staining for the purposes of treatment planning, ideally with a consensus approach in difficult cases."

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

Single-cell profiling of gastric mucosal remodeling in zolbetuximab-induced gastritis (ESMO Asia 2026) - No abstract available

Oncology

A Phase II Clinical Trial Evaluating the Antiemetic Effect and Safety of a Five-Drug Combination Therapy for Zolbetuximab, Including Olanzapine and Antihistamines, with or without Pre-Treatment Olanzapine (ESMO 2026) - No abstract available

Clinical • Combination therapy • P2 data • Oncology

Real-World Use of Zolbetuximab Plus Chemotherapy (CTx) in Patients With CLDN18.2+, HER2−, Locally Advanced (LA) Unresectable or Metastatic Gastric or Gastroesophageal Junction Cancer (mGC/GEJC) in a Canadian Patient Support Program (PSP) (ESMO 2026) - No abstract available

Clinical • Metastases • Real-world • Real-world evidence • Gastric Cancer • Oncology • Solid Tumor • CLDN18 • HER-2

Chemoimmunotherapy versus zolbetuximab-based therapy in PD-L1–low gastroesophageal adenocarcinoma: results from the AGAMENON-SEOM registry (ESMO 2026) - No abstract available

Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor

Randomized phase II trial of zolbetuximab as second-line treatment in patients with claudin 18.2-positive advanced gastric/GEJ cancer with previous zolbetuximab exposure: ZELDA. (PubMed, ESMO Gastrointest Oncol) - "To investigate whether the addition of zolbetuximab to second-line nab-paclitaxel plus ramucirumab improves overall survival (OS) in patients with CLDN18.2-positive advanced gastric or GEJ adenocarcinoma who have progressed with first-line zolbetuximab-based therapy. The primary endpoint is OS in the full analysis set. Integrated translational research (ZELDA-TR) is also planned."

Journal • P2 data • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • CLDN18 • HER-2

Current and Emerging Targeted Therapy in Advanced Gastroesophageal Adenocarcinoma. (PubMed, Pharmaceuticals (Basel)) - " HER2-directed therapy has progressed from trastuzumab through dual blockade, immunotherapy combinations, next-generation ADCs (notably trastuzumab deruxtecan) and bispecific antibodies such as zanidatamab, which has now overtaken trastuzumab in the first-line setting. CLDN18.2-targeted zolbetuximab has demonstrated survival benefit in biomarker-selected patients, with newer ADCs, BiTEs and the first approved solid-tumour CAR-T therapy (satricabtagene autoleucel) extending this target further. VEGFR2 inhibition with ramucirumab remains a cornerstone in later lines, while novel VEGF/PD-1(L1) bispecifics are under investigation. FGFR2b-targeted bemarituzumab showed early promise that weakened on phase 3 confirmation, and MET/EGFR-directed agents, including savolitinib and amivantamab, require stringent biomarker selection to demonstrate benefit amid tumour heterogeneity. Novel targeted agents, particularly to HER2 and CLDN18.2, have demonstrated survival benefit despite..."

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

EARLY AND SEVERE GASTROINTESTINAL TOXICITY WITH ZOLBETUXIMAB: A FAERS SIGNAL ANALYSIS IN GI CANCERS (UEGW 2026) - "FAERS data demonstrate a strong and clinically significant signal of gastrointestinal toxicity with zolbetuximab, characterized by high rates of nausea, vomiting, and hospitalization but no associated mortality. These findings support a predictable, on-target toxicity profile and highlight the need for proactive and optimized supportive care strategies."

Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • CLDN18

POST-MARKETING SAFETY PROFILE OF ZOLBETUXIMAB IN GASTRIC AND GASTROESOPHAGEAL JUNCTION ADENOCARCINOMA: A DISPROPORTIONALITY ANALYSIS WITH SIGNAL VALIDATION AND TEMPORAL CHARACTERIZATION (UEGW 2026) - "As with all DA, findings are hypothesis-generating and do not establish causality. Real-world data showed a reporting pattern skewed towards Japan and confirmed AEs reported in clinical trials, while some others possibly suffer from underreporting. Most of the SDRs identified were attributable to the malignancy or to chemotherapy rather than zolbetuximab."

Clinical • P4 data • Endocrine Disorders • Gastric Adenocarcinoma • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Disorder • Hypertension • Interstitial Lung Disease • Oncology • Peripheral Neuropathic Pain • Pulmonary Disease • Respiratory Diseases • Solid Tumor • CLDN18 • HER-2

Zolbetuximab-associated adverse event reporting signals in gastric cancer: a FAERS disproportionality analysis. (PubMed, Front Pharmacol) - "We conducted an indication-restricted, report-level US Food and Drug Administration Adverse Event Reporting System (FAERS) analysis from 2024 Q1 through 2026 Q1, comparing 597 zolbetuximab reports with 1,231 pooled nivolumab/pembrolizumab reports. Gastritis and findings related to albumin, protein loss, and fluid balance require clinical confirmation, while protein-losing gastroenteropathy was reported sparsely. Overall, the results characterize reporting disproportionality in an early, Japan-dominant setting, not incidence or comparative clinical risk."

Adverse events • Journal • Gastric Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor • PD-1

Making Zolbetuximab deliverable in practice: multidisciplinary management of nausea, vomiting, gastritis, and hypoalbuminemia in first-line CLDN18.2-positive, HER2-negative gastric/GEJ adenocarcinoma. (PubMed, Med Oncol) - "Throughout the review, we distinguish established evidence from hypotheses generated by clinical, endoscopic, real-world, and pharmacokinetic observations. Proactive toxicity management may preserve treatment continuity and effective drug exposure, thereby maximizing the likelihood of clinical benefit; however, prospective studies are required to determine whether supportive-care interventions directly improve efficacy outcomes."

Journal • Review • Anorexia • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Disorder • Oncology • Solid Tumor • CLDN18 • HER-2

Early Serum Protein Decline During Zolbetuximab Therapy in Gastroesophageal Adenocarcinoma: A Real-World Signal Suggestive of Protein-Losing Enteropathy (ACG 2026) - "Twenty-four patients were included. Serum albumin declined in all patients, and total protein declined in 23/24 (95.8%) immediately following treatment initiation (Figure 1). After the first cycle, median albumin decreased by 0.9 g/dL (22.8%), and total protein decreased by 1.5 g/dL (23.7%) from baseline (Figure 2)."

Clinical • Real-world • Real-world evidence • Gastroesophageal Junction Adenocarcinoma • Nephrology • Oncology • Renal Disease • Solid Tumor • CLDN18

Claudin 18.2-Targeted Therapy in Advanced Gastric and Gastroesophageal Junction Adenocarcinoma: A Systematic Review and Meta-Analysis (ACG 2026) - "Three randomized trials involving 1,233 patients were included. Zolbetuximab plus chemotherapy significantly improved OS (HR 0.71, 95% CI 0.59â0.85; P=0.0001; I²=30%) and PFS (HR 0.65, 95% CI 0.50â0.83; P=0.0006; I²=59%) compared with control therapy. CR rates were higher with zolbetuximab (RR 2.02, 95% CI 1.19â3.44; P=0.03; I²=0%), whereas ORR was not significantly different (RR 1.08, 95% CI 0.71â1.64; P=0.52; I²=34%)."

Metastases • Retrospective data • Review • Gastric Adenocarcinoma • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • CLDN18

Obstructive Jaundice Mimicking Pancreatobiliary Malignancy: A Rare Presentation of Claudin 18.2âPositive Poorly Cohesive Gastric Adenocarcinoma (ACG 2026) - "CLDN18.2 positivity (~90%) identifies this patient as a candidate for zolbetuximab-based therapy. Gastric cancer should be recognized as a rare cause of multi-level biliary obstruction."

IO biomarker • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Disorder • Hepatology • Oncology • Pruritus • Solid Tumor • CLDN18 • HER-2 • PD-L1

Successful Conversion Surgery after S-1 plus oxaliplatin Plus Zolbetuximab for Initially Unresectable Gastric Cancer with Pancreatic Invasion: A Case Report. (PubMed, Surg Case Rep) - "To our knowledge, this is the first published case describing successful conversion surgery following SOX plus zolbetuximab therapy. This case suggests that CLDN18.2-targeted therapy may facilitate curative resection in selected patients with initially unresectable gastric cancer."

Journal • Gastric Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CLDN18 • HER-2 • PD-L1

The Role of Immunotherapy in the Treatment of Metastatic Gastric Cancer (IASGO 2026) - "HERIZON-GEA-01 showed thatzanidatamab plus chemotherapy improved progression-free survival versus trastuzumab pluschemotherapy, while adding tislelizumab also produced an encouraging overall-survival benefit...Nivolumab plus ipilimumab failed to improve survival in CheckMate 649, andATTRACTION-6 increased response rate without improving overall survival and caused greater toxicity.However, in MSI-H/dMMR advanced G/GEJC, the phase II NO LIMIT trial showed robust and durableactivity with first-line nivolumab plus low-dose ipilimumab, supporting biomarker-defined dualcheckpoint blockade...The EP4 antagonist ONO-4578 plus nivolumab and chemotherapy showed encouragingphase II activity. ASP2138, a CLDN18.2/CD3 bispecific T-cell engager, is being evaluated withpembrolizumab and chemotherapy, while zolbetuximab plus nivolumab and chemotherapy showedpromising activity in ILUSTRO and is being tested in phase III LUCERNA. Future progress will depend on biomarker-driven combinations..."

IO biomarker • Metastases • Gastric Cancer • Oncology • Solid Tumor • CLDN18 • HER-2 • MSI • PD-L1 • TIGIT

Zolbetuximab plus chemotherapy versus immune checkpoint inhibitor regimens by programmed death-ligand 1 combined positive score in locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma: a Bayesian network meta-analysis. (PubMed, ESMO Open) - "These findings support a biomarker-informed treatment approach in human epidermal growth factor receptor 2 (HER2)-negative, CLDN18.2-positive advanced gastric/GEJ adenocarcinoma. In PD-(L)1 CPS ≥1 to <10, zolbetuximab plus chemotherapy demonstrated consistent efficacy and may represent a relevant option beyond PD-(L)1-driven selection. In CPS ≥10, zolbetuximab remained clinically meaningful, with efficacy comparable to select ICI-based regimens when exposure is optimized. Results should be interpreted cautiously given these are indirect comparisons and warrant confirmation in prospective studies."

Checkpoint inhibition • IO biomarker • Journal • Retrospective data • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • CLDN18 • HER-2 • PD-L1

CLARITY-Gastric 02: Sonesitatug Vedotin in Combination With Capecitabine With or Without Rilvegostomig in Participants With Advanced or Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma Expressing Claudin18.2 (clinicaltrials.gov) - P3 | N=2130 | Recruiting | Sponsor: AstraZeneca

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

ILUSTRO: Phase 2 Multicohort Trial of Zolbetuximab in Patients with Advanced or Metastatic Claudin 18.2-Positive Gastric or Gastroesophageal Junction Adenocarcinoma. (PubMed, Clin Cancer Res) - "Zolbetuximab plus mFOLFOX6 demonstrated promising efficacy in previously untreated patients with CLDN18.2-positive G/GEJ adenocarcinoma. These data support the first-line development of zolbetuximab in patients whose tumors are CLDN18.2 positive. Across cohorts, zolbetuximab treatment was tolerable with no new safety signals."

Journal • Metastases • P2 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor • CLDN18 • HER-2

A phase I/II dose escalation and expansion trial to evaluate safety and preliminary efficacy of BNT141 in patients with claudin-18.2-positive solid tumors. (ASCO 2023) - P1/2 | "The resulting antibody is sequence identical to IMAB362, a CLDN18.2-targeted antibody that provided clinical benefit as an add-on to chemotherapy in the Phase III SPOTLIGHT trial (Shitara et al.J Clin Oncol...The trial comprises 3 parts: dose escalation with BNT141 as monotherapy, dose escalation with BNT141 in combination with nab-paclitaxel and gemcitabine, and dose expansion...Sites in Spain, Portugal, Germany, Denmark, Netherlands and the UK will be opened in 2023. Clinical trial information: NCT04683939."

Clinical • P1/2 data • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CLDN18

CLDN18.2 targeting enhances chemotherapy sensitivity in pancreatic cancer cells and lung cancer organoids. (PubMed, Biochem Biophys Res Commun) - "In DAN-G cells, two independent CLDN18.2 siRNAs increased sensitivity to 5-fluorouracil. TST001 enhanced cisplatin-induced cytotoxicity in lung cancer patient-derived organoids...TST001 and IMAB362 reduced SLC7A11 mRNA, and TST001 increased RSL3 sensitivity in KATO III and NUGC4 cells...These findings support CLDN18.2 targeting as an approach to chemotherapy sensitization in the models tested. Reduced SLC7A11 expression and altered lipid-peroxidation responses are possible contributors, but their causal involvement in chemotherapy sensitization remains to be established."

Journal • Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CLDN18 • SLC7A11

Updated efficacy and safety results from phase III GLOW study evaluating zolbetuximab + CAPOX as first-line (1L) treatment for patients with claudin-18 isoform 2-positive (CLDN18.2+), HER2−, locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma (ESMO 2023) - P3 | "Background The phase 3 GLOW study showed statistically significant improvement with 1L zolbetuximab + capecitabine + oxaliplatin (CAPOX) vs placebo (PBO) + CAPOX in PFS (final; median 8.2 vs 6.8 mo, HR 0.69 [95% CI 0.54, 0.87], P = 0.0007) and OS (interim; median 14.4 vs 12.2 mo, HR 0.77 [95% CI 0.62, 0.97], P = 0.0118) in pts with CLDN18.2+, HER2−, LA unresectable or mG/GEJ adenocarcinoma. Most common TEAEs with zolbetuximab + CAPOX were nausea (zolbetuximab arm: 68.9% vs PBO arm: 50.2%), vomiting (66.1% vs 31.3%), and decreased appetite (41.3% vs 34.5%); incidences of serious TEAEs were similar between arms (48.0% vs 50.6%). Conclusions Zolbetuximab + CAPOX continued to demonstrate statistically significant improvement in PFS and OS compared with PBO + CAPOX, with no new safety signals, supporting zolbetuximab + CAPOX as a potential new option for 1L treatment of patients with CLDN18.2+, HER2−, LA unresectable or mG/GEJ adenocarcinoma."

Clinical • Late-breaking abstract • Metastases • P3 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • CLDN18 • HER-2

Advances in therapeutic approaches to gastric cancer. (PubMed, CA Cancer J Clin) - "In locally advanced disease, resection of the primary lesion and D2 lymphadenectomy, defined as dissection of lymph nodes along two levels of blood vessels supplying the stomach, remains the cornerstone of curative surgery, whereas perioperative chemotherapy, particularly oxaliplatin-based regimens, has demonstrated improved survival benefits compared with surgery alone...Targeted agents include claudin 18.2 antibody, with zolbetuximab establishing a new first-line standard for claudin 18.2-positive disease, and antibody-drug conjugates, such as trastuzumab deruxtecan for human epidermal growth factor receptor 2-positive disease, both of which have revolutionized treatment paradigms. Emerging strategies include dual immune checkpoint inhibition, bispecific antibodies, chimeric antigen receptor T-cell therapy, and fibroblast growth factor receptor 2b-targeting agents. Ultimately, the field is moving toward personalized, biomarker-driven approaches within multidisciplinary..."

IO biomarker • Journal • Review • Gastric Cancer • Microsatellite Instability • Oncology • Palliative care • Solid Tumor • CLDN18 • FGFR2 • HER-2 • MSI • PD-L1

Zolbetuximab plus gemcitabine and nab-paclitaxel (GN) in patients (pts) with claudin 18 isoform 2 (CLDN18.2)+ metastatic pancreatic adenocarcinoma (mPAC): phase II GLEAM study (ESMO-GI 2026) - P2 | "Conclusions Blood biomarker results suggest a subset of patients with CLDN18.2+ mPAC may benefit from zolbetuximab. IL-18 levels may be associated with clinical benefit to zolbetuximab in pts with mPAC."

Clinical • Metastases • P2 data • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • CLDN18 • IL18

Zolbetuximab + mFOLFOX6 as first-line (1L) treatment for patients (pts) with claudin-18.2+ (CLDN18.2+) / HER2− locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma: Primary results from phase 3 SPOTLIGHT study (ASCO-GI 2023) - P3 | " Previously untreated pts with CLDN18.2+ (moderate-to-strong membrane staining in ≥75% tumor cells by IHC)/HER2− LA unresectable or mG/GEJ adenocarcinoma were randomized 1:1 to zolbetuximab IV 800 mg/m2 (cycle [C] 1, day [D] 1) followed by 600 mg/m2 (C1D22, and every 3 weeks in later cycles) + mFOLFOX6 IV (D1, 15, 29) for four 42-day cycles vs placebo + mFOLFOX6; pts without PD continued for >4 cycles with zolbetuximab or placebo, + folinic acid and 5-FU at investigator’s discretion until PD or discontinuation criteria were met... Targeting CLDN18.2 with 1L zolbetuximab combined with mFOLFOX6 statistically significantly prolonged PFS and OS in pts with CLDN18.2+/ HER2−, LA unresectable or mG/GEJ adenocarcinoma. TEAEs were consistent with previous studies. Zolbetuximab + mFOLFOX6 may be a new option for these pts."

Clinical • Late-breaking abstract • Metastases • P3 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • CLDN18 • HER-2