A Phase Ib Trial Evaluating the Safety and Activity of Neoadjuvant Combination of Tislelizumab Plus FLOT for Resectable Esophagogastric Adenocarcinoma

NCT07059299 | Recruiting Phase 1

• 2 other identifiers: UCCL-IKF-NeoTISLEGA2024-519993-38-00
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 4

Brief Summary

With this trial, we aim to evaluate a new combination therapy with tislelizumab and FLOT chemotherapy before surgery (neoadjuvant) for locally advanced, resectable adenocarcinoma of the esophagus or stomach (EGA). The aim of this phase Ib trial is to determine whether this combination is safe and clinically active enough to support the continuation of this concept in subsequent trials investigating novel drug combinations in the neoadjuvant setting of locally advanced EGA. As many patients are unable to tolerate the postoperative part of the standard therapy concept, we aim here to assess a prolongation of preoperative therapy to 6 or 8 applications of FLOT, instead of the routinely administered 4 pre- and 4 postoperative applications, in combination with tislelizumab.

Conditions

Gastric Adenocarcinoma; Esophagogastric Junction Adenocarcinoma; Esophageal Adenocarcinoma; Resectable Esophagogastric Adenocarcinoma; Neoadjuvant Therapy

Keywords

gastric cancer; FLOT; Tislelizumab; neoadjuvant

Outcome Measures

Primary Outcomes (1)

• Feasibility rate

  Feasibility rate, defined as proportion of patients receiving the protocol treatment before surgery ('neoadjuvant') according to the planned schedule without occurrence of at least one dose-limiting toxicity (DLT).

  up to 8 months

Study Arms (1)

Dose intensification (Level 1 and 2)

EXPERIMENTAL

In the dose intensification part of the trial, eligible patients will be enrolled in a staggered approach with 6 patients for each successive dose level: Dose level 1 (n=6): * 4 cycles tislelizumab (200 mg, i.v. on day 1 Q3W ) plus * 6 cycles: FLOT (docetaxel 50 mg/m², oxaliplatin 85 mg/m², leucovorin 200 mg/m² and 5-FU (5-fluorouracil) 2600 mg/m², all i.v. on day 1 Q2W) Dose level 2 (n=6): * 5 cycles tislelizumab (200 mg, i.v. on day 1 Q3W) plus * 8 cycles: FLOT (docetaxel 50 mg/m², oxaliplatin 85 mg/m², leucovorin 200 mg/m² and 5-FU 2600 mg/m², all i.v. on day 1 Q2W) The maximum dose level at which one or less out of 6 patients experienced a DLT is considered an optimal dose. In the expansion part of the trial, the dose level classified as optimal dose will be extended by a further 6 patients (12 patients in total for the optimal dose level).

Drug: Tislelizumab; Drug: FLOT Chemotherapy

Interventions

Tislelizumab DRUG

humanized immunoglobulin G4 (IgG4)-variant monoclonal antibody (mAb) against human programmed cell death-1 (PD-1)

Dose intensification (Level 1 and 2)

FLOT Chemotherapy DRUG

docetaxel 50 mg/m², oxaliplatin 85 mg/m², leucovorin 200 mg/m² and 5-FU 2600 mg/m², all i.v. on day 1 Q2W

Dose intensification (Level 1 and 2)

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 ≥ 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, esophageal or esophagogastric junction adenocarcinoma that:
• Is considered technically resectable.
• Does not involve distant site of the peritoneal cavity.
• confirmed by diagnostic laparoscopy for all patients with tumors located in the stomach and those with type 2 and 3 GEJ adenocarcinomas according to ESMO guideline recommendation \[Lordick et al. 2022\].
• Type 1 GEJ and esophageal adenocarcinomas can be enrolled without diagnostic laparoscopy (which is in line with guidelines and the current routine practice in Germany).
• Tumor material is available for local assessment of PD-L1 (CPS) and dMMR/MSI-status at the investigator´s site.
• Patient has an ECOG performance status 0 or 1.
• Patients has adequate blood count, liver-enzymes, and renal function:
• ANC (Absolute neutrophil count) \> 1,500 cells/μL without the use of hematopoietic growth factors.
• Platelet count ≥ 100 x 10\^9/L (\>100,000 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.

You may not qualify if:

• Patient received previous (radio)chemotherapy or immunotherapy for the same condition or within the past five years for any other cancerous condition.
• Patient received prior partial or complete esophagogastric resection.
• Patient has known hypersensitivity to any component of the tislelizumab 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 randomization, severe asthma, severe COPD, restrictive lung disease, pleural effusion etc.).
• 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 study enrollment.
• Patients has pernicious anemia or other megaloblastic anemia due to vitamin B12 deficiency.
• Patient has peripheral sensitive neuropathy with functional deficits.
• 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 triplicate12-lead ECG.
• Participant has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• Patient has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
• Patient has active primary immunodeficiency, known uncontrolled active HIV infection or active hepatitis B or C (HBV/HCV) infection. Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA. Subjects with past or resolved HBV infection are eligible only if they meet all of the following criteria:

Sponsors & Collaborators

• BeiGene: collaborator
• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead
• Universitätsklinikum Leipzig: collaborator

Study Sites (4)

Krankenhaus Nordwest GmbH Institut für Klinisch-Onkologische Forschung (IKF)

Frankfurt, 60488, Germany

RECRUITING

Hämatologisch-Onkologische Praxis Eppendorf (hope)

Hamburg, 20249, Germany

NOT YET RECRUITING

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

NOT YET RECRUITING

Klinikum rechts der Isar München der TU München

München, 81675, Germany

RECRUITING

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus; Stomach Neoplasms

Interventions

tislelizumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Study Officials

• Florian Lordick, Prof. Dr.

  Universitätsklinikum Leipzig

  PRINCIPAL INVESTIGATOR

• Salah Eddin Al-Batran, Prof. Dr.

  Frankfurter Institut für Klinische Krebsforschung IKF GmbH

  STUDY CHAIR

Central Study Contacts

Florian Lordick, Prof. Dr.

CONTACT

+49 341 97 12560; Florian.lordick@medizin.uni-leipzig.de

Claudia Pauligk, Dr.

CONTACT

+49 (0) 69 / 5899 787 - 52; neotislega@ikf-khnw.de

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2025
• First Posted: July 10, 2025
• Study Start: December 12, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: December 19, 2025

Record last verified: 2025-12

Locations

DE (4)