How does DataLookout track Claudin 18.2 competitive intelligence?

DataLookout monitors ClinicalTrials.gov daily for CLDN18.2 trial activity — including zolbetuximab combination trials in pancreatic cancer and early-stage gastric cancer, ADC Phase 1 dose-escalation completions and Phase 2 initiations, bispecific antibody registrations (AZD5335, REGN5668), and CAR-T trial expansions. Sponsor-based watchlists allow BD teams to track all Astellas, AstraZeneca, or Regeneron CLDN18.2 activity in a single dashboard with daily change alerts.

Claudin 18.2 Clinical Trials — Zolbetuximab, CLDN18.2 ADC & CAR-T Pipeline 2026

Q: What is the CLDN18.2 target and what tumors express it?

Claudin 18.2 (CLDN18.2) is a tight junction protein normally restricted to gastric mucosa. It is a splice variant of Claudin 18 that becomes aberrantly expressed on the surface of tumor cells when tight junctions disrupt during malignant transformation — making its extracellular epitope accessible to therapeutic antibodies. CLDN18.2 is expressed in approximately 38-40% of gastric/GEJ adenocarcinomas (at ≥2+ IHC intensity in ≥75% of cells), 50-60% of pancreatic ductal adenocarcinoma, 15-20% of biliary tract cancers, and smaller subsets of lung adenocarcinoma and ovarian cancer. It does not overlap with HER2 positivity — CLDN18.2 defines a distinct patient population.

Q: What CLDN18.2 ADCs are in clinical development?

Multiple CLDN18.2-directed ADCs are in Phase 1/2 development. Key programs include: SYSA1801 (Sorrento/Sienna Biopharmaceuticals, auristatin payload), TST001 (TST Biomedical), CMG901 (Keymed Biosciences/AstraZeneca, MMAE payload), and AB011 (Abdera Therapeutics). The ADC approach addresses a limitation of zolbetuximab — it requires high CLDN18.2 expression for efficacy. ADCs with cytotoxic payloads may be active at lower expression levels. CMG901 is the most advanced, with AstraZeneca having in-licensed global rights and running Phase 2 studies in gastric, GEJ, and pancreatic cancer.

120+

Active CLDN18.2 Trials

FDA-Approved Agent (2024)

40%

Gastric Tumors CLDN18.2+

Modalities in Trials

FDA Approval Alert (March 2024): Zolbetuximab (Vyloy, Astellas) received FDA approval for first-line treatment of CLDN18.2-positive, HER2-negative gastric/GEJ adenocarcinoma in combination with FOLFOX or CAPOX. This is the first approval of a CLDN18.2-directed therapy globally and creates companion diagnostic demand for CLDN18.2 IHC testing.

Approved Agents

Drug	Sponsor	Mechanism	Indication	Status
Zolbetuximab (Vyloy)	Astellas	Anti-CLDN18.2 mAb (ADCC/CDC)	1L HER2− CLDN18.2+ Gastric/GEJ + FOLFOX or CAPOX	FDA Approved Mar 2024

Phase 3 Programs

Trial	Drug / Regimen	Sponsor	Setting	Status
NCT03504397 SPOTLIGHT	Zolbetuximab + mFOLFOX6 vs Placebo + mFOLFOX6	Astellas	1L CLDN18.2+ HER2− Gastric/GEJ	Completed (Pivotal) Phase 3
NCT03653507 GLOW	Zolbetuximab + CAPOX vs Placebo + CAPOX	Astellas	1L CLDN18.2+ HER2− Gastric/GEJ	Completed (Pivotal) Phase 3
NCT05568095	Zolbetuximab + Pembrolizumab + FOLFOX/CAPOX	Astellas / MSD	1L Gastric/GEJ (combination with PD-1)	Recruiting Phase 3
NCT05645094 CMG901-003	CMG901 (CLDN18.2 ADC) vs Physician Choice	AstraZeneca / Keymed	2L+ Gastric/GEJ/Pancreatic CLDN18.2+	Recruiting Phase 3

Phase 1/2 Pipeline — ADCs, Bispecifics, CAR-T

Drug	Sponsor	Modality / Payload	Indications	Phase
CMG901	AstraZeneca / Keymed Biosciences	ADC — MMAE payload	Gastric, GEJ, Pancreatic	Phase 2/3
SYSA1801	Sorrento / Sienna Biopharmaceuticals	ADC — auristatin (MMAE)	Gastric, GEJ, Pancreatic	Phase 2
TST001	TST Biomedical / Jiangshu Hengrui	Anti-CLDN18.2 mAb	Gastric/GEJ + chemotherapy	Phase 2
AZD5335	AstraZeneca	Bispecific — CLDN18.2 × CD3	Gastric, GEJ, Pancreatic	Phase 1
REGN5668	Regeneron	Bispecific — CLDN18.2 × MUC17	Gastric/GEJ	Phase 1
CT041 (satricabtagene autoleucel)	CARsgen Therapeutics	CAR-T — anti-CLDN18.2	Gastric, Pancreatic	Phase 2
LB-1908	Lianbia Biosciences	ADC — topoisomerase I inhibitor	Gastric, Pancreatic	Phase 1
QLS31904	Qilu Pharmaceutical	Anti-CLDN18.2 mAb + PD-1	Gastric/GEJ	Phase 2

The Biology: Why CLDN18.2 Is a Druggable Target

Claudin 18.2 (CLDN18.2) is a transmembrane tight junction protein normally expressed only in the stomach's gastric mucosa, where it is buried within cell-cell junctions and inaccessible to systemic antibodies. During malignant transformation, tight junction architecture breaks down — exposing the extracellular domain of CLDN18.2 on the tumor cell surface. This aberrant surface expression creates a tumor-selective target: the epitope is present on cancer cells but not on normal gastric tissue (which retains CLDN18.2 in tight junctions) or other normal tissues.

This selectivity is the source of CLDN18.2's therapeutic appeal. Unlike broadly expressed targets that require careful dose optimization to spare normal tissue, CLDN18.2's conformation-dependent exposure on cancer cells provides a window for tumor-selective killing with acceptable safety.

CLDN18.2 expression is assessed by immunohistochemistry (IHC) using the VENTANA CLDN18 (43-14A) antibody (Roche). Positive status for zolbetuximab trials was defined as ≥75% of tumor cells with ≥2+ staining intensity — a threshold that captures approximately 38-40% of gastric/GEJ tumors. A separate cohort with ≥1+ expression represents a larger population being explored in zolbetuximab combination trials.

SPOTLIGHT and GLOW: What the Pivotal Trials Showed

Zolbetuximab's FDA approval rested on two concordant Phase 3 trials:

SPOTLIGHT (NCT03504397): 565 patients with 1L HER2−, CLDN18.2+ (≥75% ≥2+) gastric/GEJ adenocarcinoma. Zolbetuximab + mFOLFOX6 vs placebo + mFOLFOX6. Median PFS: 10.61 vs 8.67 months (HR 0.751, p=0.0066). Median OS: 18.23 vs 15.54 months (HR 0.750, p=0.0053). Both co-primary endpoints met.
GLOW (NCT03653507): 507 patients, same eligibility criteria. Zolbetuximab + CAPOX vs placebo + CAPOX. Median PFS: 8.21 vs 6.80 months (HR 0.687, p=0.0007). Median OS: 14.39 vs 12.16 months (HR 0.771, p=0.0118). Both co-primary endpoints met.

The incremental benefit is modest in absolute terms (1.5-2 months PFS, 2-3 months OS), but statistically robust with both trials positive. The toxicity profile adds nausea and vomiting from CLDN18.2 inhibition in normal stomach — typically manageable with antiemetics but a clinically meaningful addition to chemotherapy-associated GI toxicity.

Competitive Watch: Zolbetuximab's benefit is additive to chemotherapy but does not eclipse the HER2+ standard (trastuzumab+chemotherapy, ToGA). The HER2−/CLDN18.2+ population zolbetuximab serves had no approved targeted therapy prior to 2024. The next competitive question is whether combining zolbetuximab + PD-1 checkpoint inhibition + chemotherapy improves outcomes vs either doublet — the combination trials (e.g., with pembrolizumab, NCT05568095) will define the 3-drug standard.

CLDN18.2 Beyond Gastric Cancer

The target's expression profile in non-gastric tumors has generated significant trial activity:

Pancreatic ductal adenocarcinoma (PDAC): CLDN18.2 is expressed in 50-60% of PDAC tumors — a higher prevalence than gastric cancer. PDAC has historically lacked targetable alterations (except KRAS G12C/D in small subsets, BRCA1/2 germline), making CLDN18.2 a meaningful new target. CMG901 (AZ/Keymed) and CT041 (CAR-T, CARsgen) have both shown signals in PDAC. The challenge is PDAC's dense stroma limiting drug delivery.
Biliary tract cancer (BTC): CLDN18.2 expressed in ~15-20% of BTC, including intrahepatic cholangiocarcinoma (IHCC). Given the established FGFR2 inhibitor landscape in IHCC, CLDN18.2 may define a distinct molecular subset for combination approaches.
Lung adenocarcinoma: Low-level CLDN18.2 expression in a subset of lung adenocarcinomas has prompted basket trial enrollment, though the therapeutic relevance remains uncertain.
Ovarian cancer: Phase 1 data emerging; tumor histology-specific expression levels are under characterization.

BD Intelligence: The CLDN18.2 space is bifurcating into two distinct strategies. Strategy 1 (Astellas, TST001, QLS31904): enhance the naked antibody approach — better dosing schedules, combination with PD-1 or VEGF inhibitors. Strategy 2 (AZ/Keymed CMG901, LB-1908): deliver cytotoxic payload directly via ADC, enabling activity at lower CLDN18.2 expression levels and potentially in ADC-naive patients already treated with zolbetuximab. The ADC strategy is the more aggressive competitive challenge to Astellas: if CMG901 Phase 3 is positive, it reframes CLDN18.2 ADCs as a second-line standard in patients previously treated with zolbetuximab in the first line.

CAR-T and Bispecifics: The Emerging Modalities

CARsgen's CT041 (satricabtagene autoleucel) is the most advanced CLDN18.2 CAR-T program. Phase 2 data in heavily pretreated gastric/GEJ and pancreatic cancer showed objective responses in approximately 50% of patients with high CLDN18.2 expression, with responses durable at 6 months in responders. The CLDN18.2 CAR-T approach is particularly interesting in PDAC, where conventional therapies have limited efficacy and where the dense tumor microenvironment — a barrier for many solid tumor CAR-T programs — may be partially addressable through CLDN18.2-guided trafficking.

Bispecific antibodies targeting CLDN18.2 represent a different approach from zolbetuximab: instead of ADCC/CDC killing via Fc engagement, bispecifics redirect T-cells directly. AstraZeneca's AZD5335 (CLDN18.2×CD3) and Regeneron's REGN5668 (CLDN18.2×MUC17) are both in Phase 1. The CLDN18.2×MUC17 bispecific concept (REGN5668) is noteworthy — MUC17 is expressed on gastric cancer cells, making this a tumor-selective T-cell engager that theoretically avoids the on-target gastric mucosal toxicity risk of CLDN18.2×CD3 bispecifics.

Companion Diagnostic Landscape

The FDA approved zolbetuximab with a required companion diagnostic: the VENTANA CLDN18 (43-14A) RxDx assay (Roche). This creates a testing dependency for zolbetuximab use in the U.S. — every patient must be tested at an approved laboratory. The CDx requirement shapes the market:

Gastric/GEJ patients who are HER2+ are tested for HER2 first. Only HER2− patients proceed to CLDN18.2 testing.
CLDN18.2 testing adds cost and pathology workflow time. Community oncology adoption will depend on integrated testing panels that include both HER2 and CLDN18.2.
Multiple companies are developing alternative CLDN18.2 IHC assays; the competitive CDx market will develop as the target becomes established.

Key Data Readouts Ahead

Zolbetuximab + pembrolizumab + FOLFOX/CAPOX (NCT05568095): Triple combination in 1L gastric/GEJ. If positive, establishes a 3-drug standard and raises the bar for second-line CLDN18.2-directed ADCs.
CMG901 Phase 3 (NCT05645094): First CLDN18.2 ADC Phase 3. Positive result would validate ADC efficacy at lower CLDN18.2 expression thresholds and open second-line CLDN18.2 targeting.
CT041 Phase 2 expansion in pancreatic cancer: Signal-finding data will determine whether solid tumor CLDN18.2 CAR-T is viable — a critical question for the field.
AZD5335 Phase 1 dose escalation completion: AstraZeneca's bispecific program will reach recommended Phase 2 doses within the next 12-18 months; combination expansion cohorts with CMG901 are anticipated.

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Frequently Asked Questions

How many Claudin 18.2 clinical trials are currently active?

As of March 2026, there are approximately 120 active Claudin 18.2 (CLDN18.2) clinical trials on ClinicalTrials.gov. Astellas leads with zolbetuximab (Vyloy), the first FDA-approved CLDN18.2-targeted therapy (March 2024). AstraZeneca, Regeneron, CARsgen, and multiple Chinese biotechs have active Phase 1/2 programs across antibody, ADC, CAR-T, and bispecific modalities. The target is primarily relevant in gastric and GEJ cancer (38-40% expression prevalence), with expansion trials in pancreatic, biliary tract, and ovarian cancer.

What is zolbetuximab (Vyloy) and why was it a landmark approval?

Zolbetuximab (Vyloy, Astellas) is the first Claudin 18.2-targeted therapy approved by the FDA, receiving approval in March 2024 for first-line treatment of HER2-negative, CLDN18.2-positive gastric/GEJ adenocarcinoma in combination with FOLFOX or CAPOX chemotherapy. Two Phase 3 trials (SPOTLIGHT, GLOW) both met PFS and OS endpoints — median OS benefit of approximately 2-3 months over chemotherapy alone. Zolbetuximab is an ADCC/CDC-mechanism antibody, not an ADC — it kills tumor cells via immune effector engagement, not a cytotoxic payload.

What is the CLDN18.2 target and what tumors express it?

Claudin 18.2 is a tight junction protein restricted to gastric mucosa in normal tissue. During malignant transformation, it is aberrantly expressed on the surface of tumor cells — making it accessible to therapeutic antibodies. CLDN18.2 is expressed in approximately 38-40% of gastric/GEJ adenocarcinomas, 50-60% of pancreatic ductal adenocarcinoma, and smaller subsets of biliary tract and lung adenocarcinoma. It does not overlap with HER2 positivity — CLDN18.2 defines a distinct patient population.

What CLDN18.2 ADCs are in clinical development?

Key CLDN18.2-directed ADCs include CMG901 (AstraZeneca/Keymed, MMAE payload — most advanced, Phase 2/3), SYSA1801 (Sorrento, auristatin payload — Phase 2), and LB-1908 (Lianbia Biosciences, topoisomerase I inhibitor — Phase 1). The ADC approach may be active at lower CLDN18.2 expression levels than zolbetuximab, potentially expanding the treatable population beyond the ≥75% ≥2+ IHC threshold required for zolbetuximab.

Claudin 18.2 Clinical Trials — CLDN18.2 Pipeline 2026