CLDN18 (Claudin 18)

P1, N=18, Not yet recruiting, First Affiliated Hospital of Wenzhou Medical University

P3, N=387, Active, not recruiting, LaNova Medicines Zhejiang Co., Ltd. | Recruiting --> Active, not recruiting

P3, N=507, Active, not recruiting, Astellas Pharma Global Development, Inc. | Trial completion date: Mar 2026 --> Sep 2026

The phase III trials SPOTLIGHT and GLOW demonstrated improved survival following the addition of the CLDN18.2-targeted antibody zolbetuximab to chemotherapy...The use of different antibodies and definitions of CLDN18.2 positivity in patients with advanced G/GEJ adenocarcinoma poses a challenge for drawing definitive conclusions on the prognostic value of CLDN18.2 and association of CLDN18.2 with patient/disease characteristics. Additional research using a standardized approach to assess CLDN18.2 expression is needed.

CLDN18.2 positivity was retained in 66.7% and 73.3% of patients when applying 40% and 25% cut-off levels, respectively. CLDN18.2 expression above the ≥75% cut-off declined after zolbetuximab, but lower-level expression was often preserved, supporting the potential for subsequent targeted therapy.

Deviating test results of HER2 and PD-L1 by local and central pathology may reflect limitations in testing methodologies. In addition, these patients might not receive the most effective treatment.

Ongoing efforts to refine ADCs and explore novel formats offer significant potential to transform the treatment landscape of gastrointestinal cancers. This review examines the current state of ADC development for gastrointestinal malignancies, focusing on emerging targets and strategies beyond HER2.

P3, N=324, Recruiting, Federation Francophone de Cancerologie Digestive | Not yet recruiting --> Recruiting

These data provide an expanded understanding of the molecular underpinnings of EMCG-including the first description of a SMARCA4 frameshift variant in this entity-and demonstrate that while gastrointestinal marker immunoexpression is relatively common among endometrial carcinomas, strictly defined EMCG remains rare (<1%). As awareness of this entity grows, pathologists should take care not to over-interpret gastrointestinal marker expression as stand-alone evidence of an EMCG diagnosis.

P3, N=752, Not yet recruiting, Shanghai Chia Tai Tianqing Pharmaceutical Technology Development Co., Ltd.

Combining biomarker-driven immunotherapy and targeted approaches such as PD-1 blockade in MSI-H or EBV-positive tumors, HER2-directed therapy, and CLDN18.2 inhibition, has demonstrated a paradigm shift in the clinical management. This review highlights a pathologist-centered perspective on molecularly defined subgroups, actionable biomarkers, and evolving therapeutic paradigms in CRC and GEJ carcinoma, advancing precision oncology.