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Last updated: June 20, 2026
CLDN18.2 (Claudin 18.2) is a tight-junction membrane protein normally expressed in the differentiated epithelial cells of the gastric mucosa, where it forms the cell-cell seal that protects the gastric lining from acid. CLDN18.2 is a tumor-associated antigen because in many gastric, gastroesophageal junction (GEJ), pancreatic, esophageal, and biliary cancers, the loss of tight-junction polarity exposes CLDN18.2 on the cancer-cell surface in a way that doesn't happen on healthy tissue — allowing targeted antibodies, ADCs, bispecifics, and CAR-T to bind selectively. CLDN18.2 is a sister isoform of CLDN18.1 (lung), a separate target.
Eligibility testing uses immunohistochemistry (IHC) on tumor tissue. The FDA-approved zolbetuximab companion diagnostic (VENTANA CLDN18 [43-14A] RxDx Assay) defines CLDN18.2-positive as ≥75% of tumor cells with moderate-to-strong (2+/3+) membrane staining. Approximately 35-40% of gastric/GEJ adenocarcinoma meets this cutoff; rates differ in other tumor types. Some investigational trials use lower cutoffs (≥40%) or different antibody clones — read trial-specific eligibility carefully.
Four modality classes target CLDN18.2 in current development: monoclonal antibodies (zolbetuximab, osemitamab) + ADCs with cytotoxic payloads (8 agents) + bispecifics with CD3 T-cell engagement (AZD5863, JS107) + CAR-T with engineered patient T cells (CT041, CBG131, KD-496). This is the most modality-diverse single-target class in current oncology.
| Drug | Sponsor | Modality | Regulatory Status | Lead Recruiting Indications |
|---|---|---|---|---|
| Zolbetuximab (Vyloy, IMAB362) | Astellas | Monoclonal antibody (ADCC/CDC) | FDA Oct 2024: CLDN18.2+ HER2- gastric/GEJ adenocarcinoma + chemo. SPOTLIGHT + GLOW pivotals. NMPA approved. | Gastric/GEJ 1L (Ph3 + pembro + chemo NCT06901531) + expansion |
| AZD0901 (CMG901) | AstraZeneca / Keymed Biosciences | ADC (MMAE payload) | Investigational. Ph2 in CLDN18.2+ advanced solid tumors. Acquired by AstraZeneca from Keymed. | Cross-cancer solid tumor basket (NCT06219941) |
| IBI343 | Innovent Biologics | ADC | Investigational. Phase 3 monotherapy vs placebo in previously-treated gastric (NCT07066098). Phase 2 neoadjuvant pancreatic (NCT07415525). | Gastric (Ph3 2L+), Pancreatic (Ph2 neoadjuvant), Biliary |
| LM-302 (TPX-4589) | LaNova Medicines (BioNTech-acquired Oct 2023) | ADC | Investigational. Phase 3 + tislelizumab (NCT07385703). Multiple Ph2 combos with chemo + IO. | Gastric/GEJ (Ph3), Pancreatic (Ph2) |
| SHR-A1904 | Hengrui Pharma | ADC | Investigational. Phase 3 vs investigator's choice in CLDN18.2+ patients (NCT06649292). Combination Phase 1 trials open. | Gastric/GEJ (Ph3), Solid tumor basket |
| RC118 | RemeGen | ADC | Investigational. Phase 1/2 monotherapy + toripalimab combination (NCT06038396). | Gastric, Pancreatic |
| QLS31905 (ANO31905) | Qilu Pharma | ADC | Investigational. Multiple Ph2 combos with chemo + IO + cadonilimab. | Gastric, Pancreatic |
| Sonesitatug Vedotin | (sponsor per trial) | ADC (vedotin payload) | Investigational. Phase 3 + capecitabine ± rilvegostomig (NCT07431281). | CLDN18.2+ advanced (Ph3) |
| Osemitamab (TST001) | Transcenta | Monoclonal antibody | Investigational. Phase 3 first-line gastric/GEJ + pembrolizumab + chemo (NCT06093425). | Gastric/GEJ (Ph3 1L) |
| AZD5863 | AstraZeneca | Bispecific (CLDN18.2 × CD3, T-cell engager) | Investigational. Phase 1/2 in advanced solid tumors (NCT06005493). | Solid tumor basket (Ph1/2) |
| JS107 | Shanghai Junshi | Bispecific (CLDN18.2 × CD3) | Investigational. Phase 3 1L + toripalimab + chemo (NCT07584135) + Phase 3 2L+ vs investigator's choice (NCT07284134). | Gastric/GEJ (Ph3 1L + 2L+) |
| CT041 (satricabtagene autoleucel, satri-cel) | CARsgen Therapeutics | CAR-T (autologous) | Investigational. Phase 2/3 in heavily-pretreated gastric/GEJ (registrational Ph2 NCT04581473 readout positive in MRD-eligible CLDN18.2+ patients). Phase 1 pancreatic adjuvant (NCT05911217) + Phase 1 gastric/GEJ adjuvant (NCT06857786). | Gastric/GEJ (heavily pretreated + adjuvant), Pancreatic (adjuvant) |
| CBG131 | (sponsor per trial) | CAR-T | Investigational. Phase 1 in CLDN18.2-positive advanced cancers (NCT07394205). | Solid tumor basket |
| Dual CLDN18.2 × PD-L1 CAR-T | Multiple | CAR-T | Investigational. Phase 1 dual-targeting CLDN18.2 + PD-L1 (NCT06084286). | CLDN18.2+ advanced solid tumors |
| KD-496 | (sponsor per trial) | CAR-T (NKG2D × CLDN18.2 dual) | Investigational. Phase 1 NKG2DL+/CLDN18.2+ solid tumors (NCT06134960). | NKG2DL+/CLDN18.2+ solid tumors |
The only FDA-approved CLDN18.2-targeted therapy. FDA initial approval October 18, 2024 in combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic CLDN18.2-positive HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma. Approval based on the SPOTLIGHT (NCT03504397) Phase 3 trial of zolbetuximab + mFOLFOX6 vs placebo + mFOLFOX6 and the GLOW (NCT03653507) Phase 3 trial of zolbetuximab + CAPOX vs placebo + CAPOX — both met their progression-free survival and overall survival primary endpoints in CLDN18.2-positive (≥75%) HER2-negative patients. CLDN18.2 IHC testing required upfront. Side-effect signal: nausea and vomiting are class-defining (very common, often grade 3+; aggressive antiemetic prophylaxis required), plus fatigue, abdominal pain, anemia, neutropenia from the chemotherapy backbone. Phase 3 expansion trials open: NCT06901531 tests zolbetuximab + pembrolizumab + chemo as 1L, advancing toward triplet IO combinations.
CARsgen Therapeutics's autologous CD8 CAR-T targeting CLDN18.2. The registrational Phase 2 NCT04581473 in heavily-pretreated CLDN18.2+ gastric/GEJ adenocarcinoma met its primary endpoint and supports a regulatory submission. Beyond the heavily-pretreated setting, the Phase 1 program is moving into the adjuvant / post-resection setting: NCT05911217 evaluates CT041 after adjuvant chemotherapy in pancreatic adenocarcinoma (one of the trials in the pancreatic disease page top results); NCT06857786 evaluates CT041 as postoperative adjuvant for gastric/GEJ. The adjuvant strategy addresses the highest-need population: post-curative-resection patients with high relapse risk. CT041 toxicity profile includes cytokine release syndrome (CRS), gastric / gastrointestinal toxicity from on-target healthy-tissue binding (CLDN18.2 is expressed in healthy gastric mucosa), and cytopenia — manageable in specialty centers with apheresis and CAR-T infrastructure.
AstraZeneca's CLDN18.2 ADC, acquired from Keymed Biosciences. MMAE-payload ADC with phase 2 monotherapy data in heavily-pretreated CLDN18.2-positive gastric/GEJ patients. Phase 2 NCT06219941 in advanced solid tumors expressing CLDN18.2 is the lead study; combination registration trials in earlier disease are expected to follow.
Innovent's CLDN18.2 ADC. Phase 3 NCT07066098 (IBI343 monotherapy vs placebo) in previously-treated CLDN18.2+ gastric/GEJ — the only single-agent CLDN18.2 ADC Phase 3 in this design. Phase 2 NCT07415525 evaluates IBI343 + chemotherapy as neoadjuvant therapy in borderline resectable pancreatic adenocarcinoma — one of the most aggressive moves of CLDN18.2 ADC into earlier-stage disease.
LaNova Medicines's CLDN18.2 ADC, acquired by BioNTech in October 2023. Phase 3 NCT07385703 tests LM-302 + tislelizumab vs standard of care in CLDN18.2+ unresectable disease. Phase 2 combinations with cadonilimab + S-1 + intraperitoneal chemo (NCT06519591) and with cadonilimab + capecitabine (NCT06587425) for gastric/GEJ. Phase 2 NCT07108504 tests LM-302 + gemcitabine in CLDN18.2+ pancreatic.
Hengrui's CLDN18.2 ADC. Phase 3 NCT06649292 vs investigator's choice of therapy in CLDN18.2-positive advanced patients. Phase 1 combination trials in CLDN18.2-positive advanced solid tumors (NCT06350006).
Transcenta's CLDN18.2 monoclonal antibody. Phase 3 NCT06093425 tests osemitamab + pembrolizumab + chemotherapy as first-line treatment in HER2- gastric/GEJ adenocarcinoma — a head-to-head competitive position with zolbetuximab in the 1L gastric/GEJ setting.
AstraZeneca's CLDN18.2 × CD3 bispecific (TCE). Phase 1/2 NCT06005493 in advanced or metastatic solid tumors expressing CLDN18.2 — the lead bispecific TCE for this target.
Junshi's CLDN18.2 × CD3 bispecific. Two concurrent Phase 3 trials: NCT07584135 (JS107 + toripalimab + chemo as 1L for CLDN18.2+ gastric/GEJ) and NCT07284134 (JS107 vs investigator's choice as 2L+ in CLDN18.2+ advanced gastric).
Vedotin-payload (MMAE) CLDN18.2 ADC. Phase 3 NCT07431281 tests sonesitatug vedotin + capecitabine ± rilvegostomig (AstraZeneca PD-1/TIGIT bispecific). Cross-mechanism combination — CLDN18.2 ADC + PD-1/TIGIT bispecific.
RC118: Phase 1/2 monotherapy (NCT05205850) + Phase 1/2 + toripalimab (NCT06038396). QLS31905: Phase 2 combinations with QL1706, QL2107, chemotherapy across gastric and pancreatic (NCT06446388, NCT06942767, NCT07151872) — the deepest combination footprint of any single CLDN18.2 ADC in development.
The 43 recruiting (and 18 not-yet-recruiting) CLDN18.2-targeted trials are grouped by primary cancer type below. CLDN18.2 IHC testing is required upfront — ask your oncologist for pathology CLDN18.2 IHC results (with the staining intensity and percentage) before screening for any CLDN18.2 trial.
The primary CLDN18.2 indication where zolbetuximab is FDA-approved. Phase 3 1L expansion and head-to-head challenger trials dominate this space.
An emerging high-impact CLDN18.2 indication. CT041 is in Phase 1 as adjuvant post-chemo; multiple CLDN18.2 ADCs are testing combinations in advanced disease and neoadjuvant settings.
A small but emerging CLDN18.2 indication. Most biliary CLDN18.2 trials are basket cohorts or combination expansions.
Cross-cancer basket studies enrolling CLDN18.2-positive solid tumors regardless of primary site. Useful for patients with less common CLDN18.2-expressing cancers (esophageal, ovarian, lung adenocarcinoma).
CAR-T trials concentrated in heavily-pretreated patients in the metastatic setting and increasingly in the adjuvant / post-resection setting. CAR-T eligibility requires apheresis-capable centers and tolerance of CRS / ICANS / cytopenia management.
Showing 43 RECRUITING + 18 not-yet-recruiting CLDN18.2-targeted interventional trials in the ClinTrialFinder corpus as of June 20, 2026. Trials enrolling only into completed cohorts and non-CLDN18.2 isoforms (CLDN18.1, CLDN6) are out of scope. For the latest searches: zolbetuximab, Claudin 18.2, CT041, AZD0901.
CLDN18.2 targeted therapy is one of three biomarker-defined classes in HER2-negative gastric/GEJ adenocarcinoma. The three-class comparison below frames where CLDN18.2 fits:
| Class | Eligibility | FDA-approved drugs | Distinctive trade-offs |
|---|---|---|---|
| CLDN18.2 Targeted Therapy (this page) | CLDN18.2 ≥75% IHC + HER2- | Zolbetuximab (Vyloy, Oct 2024) | Modest monotherapy activity (must combine with chemo); class-defining nausea/vomiting; ~35-40% of gastric/GEJ are CLDN18.2-positive at the ≥75% cutoff |
| PD-L1 IO + Chemo | PD-L1 CPS ≥1 (or ≥5 depending on agent/region) | Nivolumab + chemo (CheckMate 649); pembrolizumab + chemo + trastuzumab for HER2+ (KEYNOTE-811) | The dominant 1L combination class in PD-L1-positive HER2- gastric/GEJ today. Immune-related adverse events; PD-L1 positivity varies in measurement. |
| Chemotherapy alone | No biomarker selection | FOLFOX, CAPOX, FLOT (neoadjuvant) | The default backbone for all patients; new biomarker-targeted classes are added ON TOP of chemo, not REPLACING it. |
How CLDN18.2 + zolbetuximab is positioned in practice. The current standard 1L for HER2- gastric/GEJ is chemotherapy + PD-L1 IO (in PD-L1+) OR chemotherapy alone (PD-L1-). Zolbetuximab + chemo enters this space as an alternative for CLDN18.2-positive patients (with or without PD-L1 positivity, depending on prescribing decision). The 1L expansion trials — zolbetuximab + pembrolizumab + chemo (NCT06901531), osemitamab + pembrolizumab + chemo (NCT06093425), JS107 + toripalimab + chemo (NCT07584135) — are testing triplet IO combinations that would incorporate CLDN18.2 targeting alongside the current IO + chemo standard. HER2-positive gastric/GEJ patients should NOT receive zolbetuximab — see the HER2 ADCs mechanism hub for that population.
Cross-trial efficacy comparisons between CLDN18.2 ADCs, bispecifics, CAR-T, and antibody-only zolbetuximab without head-to-head randomized data are not reliable. The choice of CLDN18.2-targeting strategy is a discussion with the patient's medical oncologist and (for CAR-T) the cellular-therapy team.
CLDN18.2 therapies share a payload + on-target signal reflecting where CLDN18.2 is normally expressed (gastric mucosa):
What is CLDN18.2 (Claudin 18.2)?
CLDN18.2 (Claudin 18.2) is a tight-junction membrane protein normally expressed in the differentiated epithelial cells of the gastric mucosa, where it helps seal the spaces between cells. CLDN18.2 is a tumor-associated antigen because in many gastric, gastroesophageal junction (GEJ), pancreatic, esophageal, and biliary cancers it becomes exposed on the cancer-cell surface (loss of tight-junction polarity), allowing targeted antibodies and antibody-drug conjugates to bind the protein selectively on tumor cells. CLDN18.2 is a sister isoform of CLDN18.1 (lung), which is a separate target — CLDN18.2 therapies are NOT directed at CLDN18.1.
How is CLDN18.2 testing done and what counts as 'positive'?
CLDN18.2 expression is assessed by immunohistochemistry (IHC) on a tumor tissue sample. The FDA-approved zolbetuximab companion diagnostic (VENTANA CLDN18 [43-14A] RxDx Assay) defines CLDN18.2-positive as ≥75% of tumor cells showing moderate-to-strong (2+/3+) membrane staining. Many clinical trials use the same ≥75% cutoff, but some accept lower cutoffs (e.g., ≥40%) or use different antibody clones — read the trial's specific CLDN18.2 eligibility carefully. CLDN18.2-positive rate in gastric/GEJ adenocarcinoma is roughly 35-40% at the ≥75% cutoff; rates differ in pancreatic, biliary, and other tumor types. CLDN18.2 expression is largely independent of HER2 status, MSI status, and PD-L1 status — patients can be CLDN18.2-positive AND HER2-positive (or HER2-negative), and treatment selection may incorporate multiple biomarkers.
Is zolbetuximab (Vyloy) approved for my cancer?
Zolbetuximab (Vyloy, Astellas) is FDA-approved October 2024 in combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic CLDN18.2-positive, HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma. The approval was based on the SPOTLIGHT (NCT03504397) and GLOW (NCT03653507) pivotal Phase 3 trials. Zolbetuximab is NOT yet FDA-approved for other cancer types — pancreatic, biliary, esophageal, lung, and other CLDN18.2-expressing tumors remain investigational settings. Readers should consult the current FDA prescribing information for the most up-to-date label.
Are there CAR-T options for CLDN18.2-positive cancer?
Yes. The most advanced CLDN18.2 CAR-T is CT041 / satricabtagene autoleucel (CARsgen Therapeutics), in Phase 2/3 for gastric/GEJ adenocarcinoma and Phase 1 in pancreatic (NCT05911217 — adjuvant post-chemotherapy) and gastric/GEJ adjuvant (NCT06857786). Other CLDN18.2 CAR-T: CBG131 (NCT07394205), dual CLDN18.2 + PD-L1 CAR-T (NCT06084286), NKG2D × CLDN18.2 CAR-T KD-496 (NCT06134960). CAR-T eligibility requires apheresis-capable centers, manageable comorbidities, and tolerance of CRS / ICANS / cytopenia management.
What's the difference between CLDN18.2 antibody, ADC, bispecific, and CAR-T?
All four modalities target the same CLDN18.2 protein on tumor cells but use different mechanisms to kill the cancer cell. Monoclonal antibody (zolbetuximab, osemitamab): binds CLDN18.2, triggers immune mechanisms (ADCC, CDC, ADCP); combined with chemotherapy because monotherapy activity is modest. ADC (AZD0901 / CMG901, IBI343, LM-302, SHR-A1904, RC118, QLS31905, sonesitatug vedotin): delivers cytotoxic payload (MMAE, MMAF, topo I) directly to CLDN18.2+ cells. Bispecific (AZD5863, JS107): binds BOTH CLDN18.2 and CD3 on T cells, recruiting T-cell killing. CAR-T (CT041, CBG131, KD-496): patient T cells engineered ex-vivo to express CLDN18.2-binding receptor, then re-infused. ADC and CAR-T are typically reserved for patients with sufficient CLDN18.2 expression and access to specialty centers.
How do I find a CLDN18.2-positive cancer trial that fits my situation?
Use ClinTrialFinder's AI-powered matching to surface CLDN18.2 trials based on your specific situation — primary cancer type (gastric/GEJ, pancreatic, biliary, esophageal, or other CLDN18.2-expressing solid tumor), CLDN18.2 IHC status (≥75% / ≥40% / unknown), HER2 status (zolbetuximab is for HER2-negative), prior therapy, line of therapy (neoadjuvant, adjuvant, 1L, 2L+), and country. Use the patient-match button below to enter the disease-specific matching wizard. Ask your oncologist for pathology CLDN18.2 IHC results — eligibility cannot be established without IHC confirmation. For broader disease landscapes, see /trials/gastric-cancer, /trials/pancreatic-cancer, and /trials/cholangiocarcinoma.
Find Matching CLDN18.2 Trials
Use ClinTrialFinder's AI-powered matching to find zolbetuximab, CT041, AZD0901, IBI343, LM-302, SHR-A1904, AZD5863, and other CLDN18.2 trials based on your cancer type, CLDN18.2 IHC status, prior therapy history, and country.
Find Matching CLDN18.2 TrialsThis page is for information only and is not medical advice. ClinTrialFinder helps you find clinical trials that may match your situation, but enrollment decisions and treatment choices should always be made with your medical oncologist (and for cell therapy, the CAR-T team). Trial eligibility, recruitment status, and treatment details can change — verify directly with the trial sponsor or on ClinicalTrials.gov before acting on any information here. FDA approval dates and indications are summarized for context only; consult the current FDA prescribing information for each drug for authoritative regulatory status.