Clinical trial · Observational

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

Molecular Characterization of Tumor-Microenvironment Interactions to Predict Drug Resistance to Perioperative Treatment in Patients With Gastric and Gastroesophageal Junction Adenocarcinoma

NCT07692477CI-TRIAL-00117401GASTROIMMUNEnot yet recruitingClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Summary

Brief summary (as posted)

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.

Conditions

Conditions (2)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Gastric Adenocarcinoma	Gastric Adenocarcinoma	ONTOLOGY_EXACT	0.98
Gastroesophageal Junction Adenocarcinoma (Siewert II-III)	Gastroesophageal Junction Adenocarcinoma	ONTOLOGY_EXACT	0.85

Interventions

Interventions (0)

Data not yet available

No intervention recorded.

Design

Arms and outcomes

Arms (1)

label
Perioperative FLOT plus Durvalumab Cohort
description
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 outcomes (1)

measure
Identification of immune and angiogenic cellular subsets associated with pathological response to perioperative FLOT plus durvalumab
timeFrame
At surgical resection (approx. 3-4 months after treatment initiation) and approx. 2 months after completion of adjuvant therapy
description
Identification of specific cellular subsets and activation/exhaustion states, assessed by scRNA-seq, TCR/BCR sequencing, and multiparametric spectral flow cytometry of tumor-infiltrating lymphocytes (TILs) and PBMCs, associated with pathological response (Tumor Regression Grade TRG 1-2) or resistance (TRG 3-4) to perioperative FLOT plus durvalumab.

Secondary outcomes (3)

Eligibility

Eligibility (as posted)

Sex: All
Minimum age: 18 Years

Show eligibility criteria text

Inclusion Criteria:

1. Histologically confirmed adenocarcinoma of the stomach (gastric cancer, GC) or gastroesophageal junction (GEJ)
2. Operable, locally advanced disease (T \>= 2 and/or node-positive) according to AJCC 8th edition staging
3. Candidate for perioperative chemotherapy with FLOT regimen combined with durvalumab, as per clinical practice
4. Age \>= 18 years
5. Provision of written informed consent prior to any study-specific procedure

Exclusion Criteria:

1. Presence of another active malignant disease
2. Advanced or metastatic gastric/GEJ cancer not eligible for surgical treatment
3. Inability or unwillingness to provide written informed consent

References

Publications (3)

BACKGROUNDAlbano F, Severini FL, Calice G, Zoppoli P, Falco G, Notarangelo T. The role of the tumor microenvironment and inflammatory pathways in driving drug resistance in gastric cancer: A systematic review and meta-analysis. Biochim Biophys Acta Mol Basis Dis. 2025 Aug;1871(6):167821. doi: 10.1016/j.bbadis.2025.167821. Epub 2025 Apr 7. PMID 40203956
BACKGROUNDJanjigian YY, Al-Batran SE, Wainberg ZA, Muro K, Molena D, Van Cutsem E, Hyung WJ, Wyrwicz L, Oh DY, Omori T, Moehler M, Garrido M, Oliveira SCS, Liberman M, Oliden VC, Smyth EC, Stein A, Bilici M, Alvarenga ML, Kozlov V, Rivera F, Kawazoe A, Serrano O, Heilbron E, Negro A, Kurland JF, Tabernero J; MATTERHORN Investigators. Perioperative Durvalumab in Gastric and Gastroesophageal Junction Cancer. N Engl J Med. 2025 Jul 17;393(3):217-230. doi: 10.1056/NEJMoa2503701. Epub 2025 Jun 1. PMID 40454643
BACKGROUNDAl-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, Kopp HG, Mayer F, Haag GM, Luley K, Lindig U, Schmiegel W, Pohl M, Stoehlmacher J, Folprecht G, Probst S, Prasnikar N, Fischbach W, Mahlberg R, Trojan J, Koenigsmann M, Martens UM, Thuss-Patience P, Egger M, Block A, Heinemann V, Illerhaus G, Moehler M, Schenk M, Kullmann F, Behringer DM, Heike M, Pink D, Teschendorf C, Lohr C, Bernhard H, Schuch G, Rethwisch V, von Weikersthal LF, Hartmann JT, Kneba M, Daum S, Schulmann K, Weniger J, Belle S, Gaiser T, Oduncu FS, Guntner M, Hozaeel W, Reichart A, Jager E, Kraus T, Monig S, Bechstein WO, Schuler M, Schmalenberg H, Hofheinz RD; FLOT4-AIO Investigators. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet. 2019 May 11;393(10184):1948-1957. doi: 10.1016/S0140-6736(18)32557-1. Epub 2019 Apr 11. PMID 30982686