Molecular Characterization of Tumor-Microenvironment Interactions to Predict Drug Resistance in Gastric and GEJ Adenocarcinoma

Sponsor
Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis
Study ID
NCT07692477
Status
Not Yet Recruiting

Notify me when recruiting opens

Save your spot on the interest list for this study. We'll keep your details with this study so our team can follow up when recruiting opens.

Not yet recruiting

Add your contact details and location so we can keep your interest tied to this study.

Conditions

  • Gastric Adenocarcinoma
  • Gastroesophageal Junction Adenocarcinoma (Siewert II-III)

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Study Details

Surgical resection remains the only curative option for resectable gastric cancer, but perioperative FLOT chemotherapy is associated with substantial rates of chemoresistance and recurrence, largely driven by marked tumor heterogeneity. Recent data from the MATTERHORN phase III trial have shown that adding durvalumab to perioperative FLOT improves pathological complete response and survival, supporting this combination as a new standard of care for resectable gastric and gastroesophageal junction adenocarcinoma. This observational multicenter study aims to characterize angiogenic and immune profiles within the tumor microenvironment and peripheral blood, in order to identify cellular and molecular signatures associated with response or resistance to perioperative FLOT plus durvalumab. Longitudinal biospecimen collection (PBMCs, serum, plasma, endoscopic biopsies, surgical specimens) will be integrated with multiparametric flow cytometry, single-cell transcriptomics and TCR/BCR sequencing, immunohistochemistry, pathomics and multiplex immunoassays, to provide mechanistic insights and potential predictive biomarkers.

Key Dates

First listed
Jul 9, 2026
Start date
Sep 1, 2026
Status verified
Jul 2026
Primary completion
Sep 1, 2027
Completion
Sep 1, 2028

Study Design

Enrollment
250 participants (estimated)

Arms

  • Arm: Perioperative FLOT plus Durvalumab Cohort
    Patients with operable, locally advanced gastric or gastroesophageal junction adenocarcinoma receiving perioperative chemotherapy (FLOT regimen: docetaxel, oxaliplatin, leucovorin, 5-fluorouracil) combined with durvalumab (anti-PD-L1) as standard of care. Longitudinal biological samples (peripheral blood and tumor tissue) are collected for molecular characterization of tumor-microenvironment interactions and identification of predictive biomarkers of pharmacological resistance.

Primary Outcome Measure

Identification of immune and angiogenic cellular subsets associated with pathological response to perioperative FLOT plus durvalumab [ Time Frame: At surgical resection (approx. 3-4 months after treatment initiation) and approx. 2 months after completion of adjuvant therapy ]

Central Contacts

Related Studies