CLDN18.2 positive

P1, N=330, Recruiting, I-Mab Biopharma US Limited | N=168 --> 330 | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2026

P2, N=151, Not yet recruiting, Suzhou Suncadia Biopharmaceuticals Co., Ltd.

Its expression was rarely observed in other histological types of lung cancer. CLDN18.2 is frequently expressed in IMAs but rarely in other major lung cancer subtypes, suggesting that zolbetuximab may represent a promising targeted therapy for IMA.

P1/2, N=84, Not yet recruiting, Anova Innovation Limited

Remnant gastric carcinoma demonstrated distinct characteristics from conventional gastric carcinoma, with highly prevalent CLDN18.2 expression. Patients with remnant gastric carcinoma may benefit from CLDN18.2-targeting therapeutics.

The target population for these recommendations is patients with unresectable locally advanced, advanced, or metastatic gastroesophageal cancer. Results from testing for actionable biomarkers should be available as soon as possible to inform treatment decision making. Immunotherapy with doublet chemotherapy is recommended for patients with proficient mismatch repair (pMMR)/microsatellite stable (MSS) human epidermal growth factor receptor 2 (HER2)-negative gastroesophageal adenocarcinoma or squamous cell carcinoma and PD-L1 expression ≥1; patients with higher PD-L1 expression are more likely to benefit from immunotherapy. Zolbetuximab is recommended for patients with gastroesophageal adenocarcinoma, PD-L1 <1, and positive CLDN18.2 expression. Patients with dual PD-L1 and CLDN18.2 positivity should engage in shared decision making, considering the factors outlined in the guideline. Doublet chemotherapy alone is recommended for patients who are not positive for actionable biomarkers or are not considered candidates for targeted therapy or immunotherapy. For patients with pMMR/MSS HER2-positive gastric/gastroesophageal junction (GEJ) adenocarcinoma, trastuzumab and doublet chemotherapy is recommended; for patients with PD-L1 expression ≥1, the addition of pembrolizumab is recommended. Immunotherapy alone or with doublet chemotherapy is recommended for patients with mismatch repair deficient/microsatellite instability-high gastroesophageal cancer. Second-line therapy options include ramucirumab with paclitaxel, trastuzumab deruxtecan for HER2-positive gastric/GEJ adenocarcinoma, and immunotherapy for PD-L1 ≥1 esophageal squamous cell carcinoma after first-line combination chemotherapy without immunotherapy.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.

AHT-102, a novel Fab-like bispecific antibody, achieves an optimized therapeutic balance through its low-affinity CD3 arm and Fc-free format. It demonstrates significant anti-tumor efficacy and exceptional targeting specificity while avoiding systemic immunotoxicity typically associated with CD3-targeting agents. These findings provide a robust scientific rationale for the clinical translation of AHT-102 in patients with CLDN18.2-positive cancers.

P2, N=180, Recruiting, I-Mab Biopharma US Limited

Collectively, these findings demonstrate that the integration of PD-1/CD28 signaling and CypA within a tri-cistronic framework significantly reinforces CAR-T cell functionality and durability. This suggests strong clinical potential as a next-generation immunotherapy for solid tumors.

P3, N=2130, Recruiting, AstraZeneca

CLDN18.2 has become a major new target in gastric cancer targeted therapy. Its clinical trials and development are advancing quickly, with various types of drugs available. In the future, more released data may make treatment strategies better and give new treatment options to gastric cancer patients.

P1/2, N=17, Recruiting, AstraZeneca AB