TNT With FLOT/Durvalumab Plus Post-OP Durvalumab for Resectable Gastroesophageal Adenocarcinoma

NCT07507968 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: IKF-099/D-FLOT-TNT
• Study Type: interventional
• Target: 101
• Locations: 2 countries
• Sites: 29

Brief Summary

This trial is designed to evaluate a total neoadjuvant approach using D-FLOT as the new standard backbone in patients with resectable esophagogastric adenocarcinoma. It addresses major limitations of current treatment paradigms, builds directly on the strong clinical signal from the MATTERHORN trial, and offers a rational, biologically sound framework for future therapy intensification and innovation. By moving systemic therapy entirely into the preoperative phase, we aim to:

• Improve patient outcomes through better adherence and deeper response
• Minimize postoperative therapy-related dropout
• Create a platform for rational post-surgical drug testing and individualized treatment escalation The trial will provide pivotal evidence to guide the next generation of curative-intent treatment strategies for EGA.

Conditions

Esophagogastric Adenocarcinoma

Keywords

neoadjuvant; gastric; esophageal; Durvalumab; FLOT chemotherapy

Outcome Measures

Primary Outcomes (1)

• Pathological complete response (pCR)

  Pathological complete response (pCR) rate as assessed locally, corresponding to the ypT0N0M0 stage category. pCR is defined as the proportion of patients with pathological complete remission in the post-surgery specimen, meaning complete absence of viable tumor cells in the primary tumor and lymph nodes and no evidence of metastatic disease upon pathological examination. For example, a patient with ypT0N0 but with pathologically confirmed peritoneal involvement containing viable tumor cells will not be considered to have achieved pCR.

  Approximately 13 months after FPI

Secondary Outcomes (7)

• Event-free survival (EFS) plus EFS-rate at 1 year

  Approximately 13 months after FPI

• Event-free survival (EFS) plus EFS-rate at 2 years

  Approximately 26 months after FPI

• Rate of patients who undergo surgery (with or without resection)

  Approximately 13 months after FPI

• R0 resection rate

  Approximately 13 months after FPI

• Assessment of postoperative ypTNM stage

  Approximately 13 months after FPI

Study Arms (1)

Durvalumab + FLOT

EXPERIMENTAL

Up to 8x preoperative cycles FLOT plus up to 4x preoperative cycles durvalumab Followed by surgical resection Followed by postoperative durvalumab (for 10 cycles)

Drug: Durvalumab

Interventions

Durvalumab DRUG

In the preoperative treatment phase, patients will receive eight 2-week cycles of FLOT chemotherapy (docetaxel 50 mg/m² IV, oxaliplatin 85 mg/m² IV, folinic acid 200 mg/m² IV, 5-FU 2,600 mg/m² IV; given on day 1 of each 2-weeks cycle \[Q2W\]). In addition, they will receive up to 4 treatments of durvalumab (1,500 mg) administrated by infusion on the first day of every second two-week cycle (Q4W). Four to eight weeks after the last dose of preoperative treatment, patients will undergo surgical resection. Study specifications for surgical resection are consistent with national guidelines. Surgical approaches will be tailored to the individual patient according to local standards with the goal of achieving R0-resection of the primary tumor. Four to twelve weeks after surgery, patients will receive durvalumab (1,500 mg IV, Q4W) monotherapy for a maximum of 10 cycles (14 cycles of durvalumab in total).

Also known as: Imfinzi

Durvalumab + FLOT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient\* has given written informed consent
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
• Patient is ≥ 18 years of age at time of signing the written informed consent
• Patient has histologically proven locally advanced (cT2-4, any cN, M0 OR any cT, cN+, M0 stage) gastric, esophagogastric junction (type 1-3) or lower esophageal adenocarcinoma that is considered medically and technically resectable
• Patient has a known PD-L1 status according to standardized TAP scoring (by local testing), any PD-L1 status is eligible
• Patient has a ECOG performance status 0 or 1
• Patient must have a life expectancy of at least 12 weeks
• Patient has adequate blood count, liver-enzymes, and renal function:
• ANC ≥ 1.0x109 cells/L without the use of hematopoietic growth factors
• Platelet count ≥ 75 x 109/L (\>75,000 per mm3)\*\*
• Hemoglobin ≥ 9 g/dL\*\*
• Serum total bilirubin ≤ 1.5x institutional upper normal limit (ULN)
• AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional ULN
• Serum Creatinine ≤ 1.5 x ULN and a calculated creatinine clearance rate \> 40 mL /min.
• Patient has a body weight \> 30 kg

You may not qualify if:

• Patient received previous (radio)chemotherapy or checkpoint inhibition for the same condition or within the past five years for any other cancerous condition
• Patient received prior partial or complete esophagogastric tumor resection
• Patient has known hypersensitivity to any component of the durvalumab formulation as well as a known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion protein and/or any known contraindication (including hypersensitivity) to one of the study drugs
• Patient has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Patient has lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (e.g., pulmonary emboli within three months of the study enrolment, severe asthma, severe COPD, restrictive lung disease, relevant pleural effusion etc.)
• Patient received a prior complete pneumonectomy
• Patient has inadequate cardiac function (LVEF value \< 50 %) as determined by echocardiography
• Patient has a known complete absence of dihydropyrimidine dehydrogenase (DPD) activity
• Patient received treatment with brivudine, sorivudine or their chemically related analogues within 28 days prior to stud enrollment
• Patients has pernicious anemia or other megaloblastic anemia due to vitamin B12 deficiency
• Patient has a medical history of myocardial infarction (MI) within 6 months before enrollment, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV). Subjects with troponin levels above ULN at screening (as defined by the manufacturer), and without any MI related symptoms should have a cardiologic consultation during screening to rule out MI
• Patient has a corrected QT interval (QTc) prolongation to \> 470 ms (females) or \>450 ms (males) based on average of the screening triplicate ECG
• Patient has a history of malignancy other than EGA except for:
• Malignancy treated with curative intent and cured with no known active disease ≥ 3 years before the first dose of study treatment and of low potential risk for recurrence.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.

Sponsors & Collaborators

• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead
• AstraZeneca: collaborator

Study Sites (29)

Charité Berlin

Berlin, Germany

Location

Vivantes Klinikum Neukölln

Berlin, Germany

Location

Universitätsklinikum Köln

Cologne, Germany

Location

Klinikum Essen Mitte

Essen, Germany

Location

Krankenhaus Nordwest

Frankfurt am Main, Germany

Location

Universitätsmedizin Göttingen

Göttingen, Germany

Location

Universitätsklinikum Halle (Saale)

Halle, Germany

Location

HOPE Hamburg Eppendorf

Hamburg, Germany

Location

UKE Hamburg

Hamburg, Germany

Location

NCT Heidelberg

Heidelberg, Germany

Location

Marien Hospital Herne

Herne, Germany

Location

Universitätsklinikum Leipzig

Leipzig, Germany

Location

RKH Klinikum Ludwigsburg

Ludwigsburg, Germany

Location

Universitätsmedizin Mainz

Mainz, Germany

Location

Universitätsmedizin Mannheim

Mannheim, Germany

Location

Universitätsklinikum Marburg

Marburg, Germany

Location

TU München

München, Germany

Location

Nürnberg Klinikum Nord

Nuremberg, Germany

Location

Caritas Klinikum Saabrücken

Saarbrücken, Germany

Location

Universitätsklinikum Ulm

Ulm, Germany

Location

Hospital Universitari Germans Trias i Pujol

Badalona, Spain

Location

Hospital General Universitari Vall d'Hebron (HUVH)

Barcelona, Spain

Location

Hospital Universitario Virgen de las Nieves de Granada

Granada, Spain

Location

Hospital Regional Universitario de Jaén

Jaén, Spain

Location

Hospital Regional Universitario de Málaga

Málaga, Spain

Location

Hospital Universitario Central de Asturias. Oncología Médica

Oviedo, Spain

Location

Hospital Universitario de Navarra (HUN)

Pamplona, Spain

Location

Hospital Clínico Universitario de Valencia Servicio de Oncología Médica

Valencia, Spain

Location

Hospital Universitario Miguel Servet Oncología Médica

Zaragoza, Spain

Location

MeSH Terms

Interventions

durvalumab

Study Officials

• Thorsten Götze, Prof. Dr.

  Krankenhaus Nordwest, Frankfurt, Deutschland

  PRINCIPAL INVESTIGATOR

• Salah-Eddin Al-Batran, Prof. Dr.

  Frankfurter Insitut für Klinische Krebsforschung IKF

  STUDY DIRECTOR

Central Study Contacts

Thorsten Götze, Prof. Dr.

CONTACT

+49 69 5899 787-19; d-flot-tnt@ikf-khnw.de

Kopp Christina

CONTACT

+49 69 5899 787-19; d-flot-tnt@ikf-khnw.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2026
• First Posted: April 2, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): February 1, 2030
• Study Completion (Estimated): February 1, 2030
• Last Updated: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (9); DE (20)