How do I know if I am eligible for zolbetuximab?

Two tests decide it: your tumor must be HER2-negative and CLDN18.2-positive (moderate-to-strong membranous CLDN18.2 in at least 75% of tumor cells by an FDA-approved IHC test). About 38% of gastric/GEJ adenocarcinomas are CLDN18.2-high. HER2, PD-L1, and CLDN18.2 are now the three routine biomarkers to test at diagnosis of advanced gastric cancer, and a tumor can be positive for more than one.

Vyloy (Zolbetuximab, IMAB362) Clinical Trials (July 2026): The First-in-Class CLDN18.2-Targeted Antibody for Gastric and Gastroesophageal Junction Cancer — Recruiting Combination Trials and the CLDN18.2 Pipeline

Last updated: July 7, 2026

Drug profile:

Vyloy (zolbetuximab, IMAB362) is the first-in-class CLDN18.2 (Claudin 18.2)-targeted monoclonal antibody, developed by Astellas. It is FDA-approved (October 18, 2024) in combination with chemotherapy for first-line CLDN18.2-positive, HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma — the first CLDN18.2-targeted therapy approved anywhere. Given by IV infusion.

Mechanism of action:

CLDN18.2 is a tight-junction protein normally buried within the stomach lining, but in gastric cancer it becomes exposed on the tumor-cell surface — a clean target. Zolbetuximab is a chimeric IgG1 antibody that binds CLDN18.2 and triggers antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), recruiting the immune system to destroy CLDN18.2-positive tumor cells.

Regulatory status:

FDA-approved October 18, 2024, with fluoropyrimidine- and platinum-based chemotherapy, for 1L locally advanced unresectable or metastatic HER2-negative, CLDN18.2-positive (moderate-to-strong membranous staining in ≥75% of tumor cells by IHC) gastric/GEJ adenocarcinoma. Based on the SPOTLIGHT (+ mFOLFOX6) and GLOW (+ CAPOX) Phase 3 trials, both positive for PFS and OS. Distinctive toxicity: infusion-associated nausea and vomiting (CLDN18.2 is also in normal gastric mucosa) — managed with antiemetic prophylaxis and infusion-rate control.

Why Vyloy Matters — In Plain Language

For years, advanced gastric cancer had two biomarker-targeted options: HER2 (trastuzumab) and PD-L1 (checkpoint immunotherapy). Most patients had neither. Zolbetuximab opened a third door: CLDN18.2. Claudin 18.2 is a protein that normally seals cells together deep in the stomach lining, hidden from the immune system — but when a stomach cell becomes cancerous, CLDN18.2 gets exposed on the cell surface, making it a target an antibody can reach. About 38% of gastric and GEJ adenocarcinomas are CLDN18.2-high, and until 2024 there was nothing to do about it.

The approval. In the SPOTLIGHT and GLOW Phase 3 trials, adding zolbetuximab to standard first-line chemotherapy improved both progression-free and overall survival in CLDN18.2-positive, HER2-negative patients — leading to the first-ever FDA approval of a CLDN18.2-targeted therapy in October 2024. CLDN18.2 is now, alongside HER2 and PD-L1, one of the three routine biomarkers to test at diagnosis of advanced gastric cancer.

What's next. The recruiting trials are pushing zolbetuximab into combinations (with checkpoint immunotherapy, with antiangiogenics) and earlier settings (neoadjuvant/perioperative). Meanwhile a whole CLDN18.2 pipeline is following behind it — bispecific T-cell engagers, ADCs, and CAR-T — validating the target zolbetuximab pioneered.

FDA-Approved Indication

First-Line CLDN18.2-Positive, HER2-Negative Gastric / GEJ Adenocarcinoma (SPOTLIGHT + GLOW)

Pivotal trials: SPOTLIGHT (zolbetuximab + mFOLFOX6) and GLOW (zolbetuximab + CAPOX), both Phase 3 · FDA: October 18, 2024 · Setting: Adults with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors are CLDN18.2-positive (moderate-to-strong membranous CLDN18.2 in ≥75% of tumor cells by an FDA-approved IHC test), first-line, with fluoropyrimidine + platinum chemotherapy · Result: both trials improved PFS and OS vs chemotherapy alone · Significance: the first CLDN18.2-targeted therapy approved — a new biomarker class in gastric cancer. Both registrational trials have completed enrollment.

★ CLDN18.2: A New Gastric-Cancer Biomarker Class

Before zolbetuximab, gastric-cancer biomarker testing meant HER2 and PD-L1. Zolbetuximab validated CLDN18.2 as a third, independent target — and the three are not mutually exclusive, so a newly-diagnosed advanced gastric/GEJ tumor should be tested for all three. CLDN18.2 positivity is defined specifically (≥75% of tumor cells with moderate-to-strong membranous IHC staining), so the test threshold matters.

Zolbetuximab is a "naked" antibody — it works through immune effector mechanisms (ADCC/CDC), not a chemotherapy payload, so it is not an antibody-drug conjugate and is given with chemotherapy rather than replacing it. The distinctive practical challenge is infusion-related nausea/vomiting, because CLDN18.2 is present in healthy stomach lining too — making antiemetic prophylaxis central to treatment.

Recruiting Zolbetuximab Combination Trials

The pivotal SPOTLIGHT and GLOW trials are complete; the recruiting zolbetuximab trials are building on that backbone with immunotherapy, antiangiogenics, and earlier disease settings (corpus-verified, July 2026).

NCT06901531 — Phase 3: Zolbetuximab + pembrolizumab + chemotherapy in locally advanced unresectable gastric cancer — adding checkpoint immunotherapy to the CLDN18.2 + chemo backbone. Status: Recruiting.
NCT06962137 — RAINSPOT, Phase 2: Zolbetuximab + paclitaxel + ramucirumab in metastatic gastric adenocarcinoma — a second-line antiangiogenic combination. Status: Recruiting.
NCT06732856 — Phase 1b/2: Neoadjuvant zolbetuximab + docetaxel-based chemotherapy in resectable gastric cancer — moving CLDN18.2 targeting into the perioperative setting. Status: Recruiting.

The Broader CLDN18.2 Pipeline (Beyond Zolbetuximab)

Zolbetuximab was first, but CLDN18.2 is now one of the most active targets in gastric — and increasingly pancreatic — cancer. Other CLDN18.2 drug classes recruiting include CLDN18.2 × CD3 bispecific T-cell engagers (e.g. ASP2138, also Astellas), other CLDN18.2 antibodies and bispecifics (spevatamig / PT886, AZD0901, ASKB589), CLDN18.2 antibody-drug conjugates, and CLDN18.2 CAR-T cell therapies. If your tumor is CLDN18.2-positive, these may be options beyond the approved zolbetuximab regimen. For the full cross-drug view of this target, see the CLDN18.2-Targeted Therapies mechanism hub.

Expected Side Effects

The defining tolerability challenge is gastrointestinal: nausea and vomiting are prominent and often occur during or shortly after the infusion, because CLDN18.2 is also expressed in the normal stomach lining. Antiemetic prophylaxis and infusion-rate management are central to zolbetuximab administration. Decreased appetite and infusion-related reactions are also common. HER2 and CLDN18.2 status must be confirmed before treatment (zolbetuximab is for HER2-negative, CLDN18.2-positive tumors).

Frequently Asked Questions

What is Vyloy (zolbetuximab) and how does it work?

Vyloy (zolbetuximab, IMAB362) is the first-in-class CLDN18.2 (Claudin 18.2)-targeted monoclonal antibody, from Astellas. CLDN18.2 is normally hidden in the stomach lining but exposed on gastric cancer cells; zolbetuximab binds it and recruits the immune system to kill those cells (ADCC/CDC). Given by IV infusion with chemotherapy.

What is Vyloy FDA-approved for?

FDA-approved Oct 18, 2024, with fluoropyrimidine + platinum chemotherapy, for first-line HER2-negative, CLDN18.2-positive (IHC ≥75% of cells) locally advanced or metastatic gastric/GEJ adenocarcinoma — the first CLDN18.2-targeted therapy approved. Based on the SPOTLIGHT and GLOW Phase 3 trials.

How do I know if I'm eligible for zolbetuximab?

Your tumor must be HER2-negative AND CLDN18.2-positive (moderate-to-strong membranous CLDN18.2 in ≥75% of tumor cells by an FDA-approved IHC test). ~38% of gastric/GEJ adenocarcinomas are CLDN18.2-high. HER2, PD-L1, and CLDN18.2 are the three routine biomarkers to test at diagnosis — a tumor can be positive for more than one.

What are the main side effects of zolbetuximab?

Prominent nausea and vomiting, often during/shortly after infusion (CLDN18.2 is in normal stomach lining too). Antiemetic prophylaxis and slower infusion rates are standard. Decreased appetite and infusion reactions are also common.

What other CLDN18.2 drugs are in trials besides zolbetuximab?

The CLDN18.2 field is expanding fast: CLDN18.2 × CD3 bispecific T-cell engagers (e.g. ASP2138), other CLDN18.2 antibodies/bispecifics (spevatamig/PT886, AZD0901, ASKB589), CLDN18.2 ADCs, and CLDN18.2 CAR-T — many in gastric and pancreatic cancer. See the CLDN18.2-Targeted Therapies hub.

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