Gastroesophageal Cancer

P2, N=27, Recruiting, Weill Medical College of Cornell University | Trial completion date: Apr 2028 --> Apr 2030 | Trial primary completion date: Apr 2026 --> Apr 2028

P1, N=398, Recruiting, Astellas Pharma Global Development, Inc. | Trial completion date: May 2027 --> May 2028 | Trial primary completion date: Nov 2026 --> May 2028

P1, N=66, Not yet recruiting, Dispatch Biotherapeutics

Notably, clinical trials are currently underway evaluating therapeutic agents targeting for instance CLDN18.2 for the treatment of gastric and gastroesophageal cancers. The aim of this work is to summarize the current knowledge about CLDNs, their presence under physiological conditions, and their role in gastrointestinal diseases.

P=N/A, N=300, Active, not recruiting, Massachusetts General Hospital | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

PD-L1 CPS is shaped by clinicopathological context and biopsy site. The persistently lower CPS ≥ 5 prevalence at SBH despite validated testing highlights assay variability and reinforces the urgent need for assay standardisation. Preferential use of primary tumor tissue may help reduce metastasis-specific bias.

Gastric or gastroesophageal junction (GEJ) cancers are usually diagnosed at advanced stages with poor prognoses and 5-year survival rates. DESTINY-Gastric05 (NCT06731478) is a global, multicenter, open-label, randomized, phase III trial to evaluate the efficacy and safety of first-line T-DXd 5.4 mg/kg plus 5-fluorouracil or capecitabine and pembrolizumab versus platinum-based chemotherapy with trastuzumab and pembrolizumab in patients with unresectable, locally advanced or metastatic, centrally confirmed HER2-positive (immunohistochemistry 3+ or immunohistochemistry 2+/in situ hybridization positive) gastric or GEJ cancer with a PD-L1 CPS ≥1. An exploratory cohort is to evaluate T-DXd plus 5-fluorouracil or capecitabine in patients with PD-L1 CPS <1.

The approved antibody zolbetuximab requires higher expression levels (≥75% of tumor cells with 2-3+ membranous staining), yet broader thresholds are increasingly explored...Broadening the threshold for positivity identified nearly three-quarters of patients as CLDN18.2 positive, underscoring the impact of selection cut points on trial eligibility. These findings highlight the potential to expand patient access to CLDN18.2-targeted therapies using lower thresholds.

Anti-CLDN18.2 therapy, primarily consisting of first-line zolbetuximab combined with chemotherapy, significantly improved progression-free survival (PFS) (hazard ratios [HR] 0.564; 95% confidence interval [CI]: 0.417-0.711) and overall survival (OS) (HR 0.716; 95% CI: 0.631-0.802), along with enhanced 1- and 2-year survival rates...Standardized definitions for CLDN18.2 positivity and high expression are urgently needed. www.crd.york.ac.uk/prospero identifier is CRD420251123719.

P1/2, N=2, Terminated, Aurigene Discovery Technologies Limited | N=18 --> 2 | Trial completion date: Nov 2028 --> Dec 2025 | Recruiting --> Terminated | Trial primary completion date: Nov 2027 --> Dec 2025; Patient recruitment problems.

P1, N=12, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2026 --> Feb 2027 | Trial primary completion date: Feb 2026 --> Feb 2027

P1, N=60, Recruiting, Memorial Sloan Kettering Cancer Center