Esophagogastric Junction AdenocarcinomaPhase 1NeoTISLEGANCT07059299
A Phase Ib Trial Evaluating the Safety and Activity of Neoadjuvant Combination of Tislelizumab Plus FLOT for Resectable Esophagogastric Adenocarcinoma
A Phase 1 study testing Tislelizumab and FLOT Chemotherapy in people with Esophagogastric Junction Adenocarcinoma and Gastric Adenocarcinoma, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 4 sites in Germany.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Esophagogastric Junction Adenocarcinoma, Gastric Adenocarcinoma, Esophageal Adenocarcinoma
- What is being tested?
- Tislelizumab and FLOT Chemotherapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 4 sitesGermany
- Study dates
- 12 Dec 2025to Aug 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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].
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- 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.
- Patients not receiving therapeutic anticoagulation must have an INR ≤ 1.5 ULN and aPTT ≤ 1.5 ULN. The use of full dose anticoagulants is allowed (according to the medical standard in the institution) and the patient has been on a stable dose for anticoagulants for at least three weeks at the time of inclusion.
- Serum Creatinine ≤ 1.5 x ULN and a calculated creatinine clearance rate ≥ 50 mL /min.
- Female patients defined as women of childbearing potential (WOCBP) must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for 4 months after last dose of tislelizumab or 6 months after the last dose of chemotherapy, whatever is later. Male patients with WOCBP partners must agree to remain abstinent (refrain from heterosexual intercourse) or use barrier contraceptives during the above period. Furthermore, male patients must refrain from donating sperm during this same period.
- There are no data that indicate special gender distribution. Therefore, patients will be enrolled gender-independently in this trial.
Who cannot join
- 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.
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- 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:
- HBsAg(-) (for > 6 months off anti-viral treatment)
- Anti-HBc(+) (IgG or total Ig)
- HBV DNA undetectable
- Absence of cirrhosis or fibrosis on prior imaging or biopsy
- Absence of HCV co-infection or history of HCV co-infection
- Access to a local hepatologist during and after the study
- Patient has active or history of autoimmune disease including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener's granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
- Patient received treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin-2) within four weeks or five half-lives of the drug, whichever is longer, prior to study enrollment.
- Patient received treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to study enrollment. The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) is allowed.
- Patient received prior allogeneic bone marrow transplantation or prior solid organ transplantation.
- Patient received live, attenuated vaccine within 30 days prior initiation of study drug.
- Patient has any other serious concomitant or medical condition that, in the opinion of the investigator, presents a high risk of complications to the patient or reduces the likelihood of clinical effect.
- Patient participated in another interventional clinical study according to Medicines Act within 28 days prior to study enrollment or participation in a clinical study according to Medicines Act at the same time as this study unless it is an observational / non-interventional study or during the follow-up period of an interventional study.
- Patient has taken an investigational drug within 28 days prior to initiation of study drug.
- Female patients, who are pregnant or breast feeding or planning to become pregnant within 7 months after the last dose of study treatment. Female patients of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study treatment.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Germany4 sites, 4 recruiting
- Recruiting
Krankenhaus Nordwest GmbH Institut für Klinisch-Onkologische Forschung (IKF)
Frankfurt, 60488
Thorsten Götze, Prof. Dr., 00496976014186, Goetze.Thorsten@KHNW.de
- Not yet recruiting
Hämatologisch-Onkologische Praxis Eppendorf (hope)
Hamburg, 20249
Alexander Stein, Prof. Dr., +49 (0) 40 36035220, stein@hope-hamburg.de
- Not yet recruiting
Universitätsklinikum Leipzig
Leipzig, 04103
Florian Lordick, Prof. Dr., +49 341 97 12560, Florian.lordick@medizin.uni-leipzig.de
Florian Lordick, Prof. Dr.
- Recruiting
Klinikum rechts der Isar München der TU München
München, 81675
Sylvie Lorenzen, Prof. Dr., 00498941401142, Sylvie.Lorenzen@mri.tum.de
About this study
Official title: NeoTISLEGA - A Phase Ib Trial Evaluating the Safety and Activity of Neoadjuvant Combination of Tislelizumab Plus FLOT for Resectable Esophagogastric Adenocarcinoma
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
- Esophagogastric Junction Adenocarcinoma, Gastric Adenocarcinoma, Esophageal Adenocarcinoma, Resectable Esophagogastric Adenocarcinoma, Neoadjuvant Therapy
- Being tested
- Tislelizumab, FLOT Chemotherapy
- Keywords
- gastric cancer, FLOT, Tislelizumab, neoadjuvant
- Medical subject headings
- Adenocarcinoma Of Esophagus, Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TislelizumabDrug
humanized immunoglobulin G4 (IgG4)-variant monoclonal antibody (mAb) against human programmed cell death-1 (PD-1)
FLOT ChemotherapyDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Tislelizumab; Drug: FLOT Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: up to 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2025
- Study start12 Dec 2025
- Primary completionAug 2027 (estimated)
- Study completionAug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Esophagogastric Junction AdenocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
- Sponsor type
- University, hospital or other
- Collaborators
- BeiGene, Universitätsklinikum Leipzig
- Responsible party
- Sponsor
- Investigators
- Florian Lordick, Prof. Dr., Principal investigator, Universitätsklinikum LeipzigSalah Eddin Al-Batran, Prof. Dr., Study chair, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07059299
- Sponsor's protocol ID
- UCCL-IKF-NeoTISLEGA
- Other IDs
- 2024-519993-38-00
- Acronym
- NeoTISLEGA
- Status last verified
- Dec 2025
- First submitted
- 3 Jun 2025
- Last updated
- 19 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NeoTISLEGA - A Phase Ib Trial Evaluating the Safety and Activity of Neoadjuvant Combination of Tislelizumab Plus FLOT for Resectable Esophagogastric Adenocarcinoma
- ClinicalTrials.gov ID
- NCT07059299
- Acronym / sponsor ID
- NeoTISLEGA / UCCL-IKF-NeoTISLEGA
- Conditions
- Esophagogastric Junction Adenocarcinoma, Gastric Adenocarcinoma, Esophageal Adenocarcinoma, Resectable Esophagogastric Adenocarcinoma, Neoadjuvant Therapy
- Keywords
- gastric cancer, FLOT, Tislelizumab, neoadjuvant
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus NordwestUniversity, hospital or other
- Collaborators
- BeiGene, Universitätsklinikum Leipzig
- Study start
- 12 Dec 2025 (actual)
- Primary completion
- Aug 2027 (estimated)
- Study completion
- Aug 2027 (estimated)
- First posted
- 10 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dose intensification (Level 1 and 2) | Experimental | Drug: Tislelizumab, Drug: FLOT ChemotherapyIn 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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:
- 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.
Key exclusion criteria (30 listed)
- 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.).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tislelizumabhumanized immunoglobulin G4 (IgG4)-variant monoclonal antibody (mAb) against human programmed cell death-1 (PD-1) | Drug | Dose intensification (Level 1 and 2) |
| FLOT Chemotherapydocetaxel 50 mg/m², oxaliplatin 85 mg/m², leucovorin 200 mg/m² and 5-FU 2600 mg/m², all i.v. on day 1 Q2W | Drug | Dose intensification (Level 1 and 2) |
Primary outcome
Feasibility rate
Time frame: up to 8 months
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).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Florian Lordick, Prof. Dr. principal investigator
Universitätsklinikum Leipzig
Salah Eddin Al-Batran, Prof. Dr. study chair
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tislelizumab and FLOT Chemotherapy in people with Esophagogastric Junction Adenocarcinoma and Gastric Adenocarcinoma, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 4 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Florian Lordick, Prof. Dr. (+49 341 97 12560, Florian.lordick@medizin.uni-leipzig.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility rate (time frame: up to 8 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2025.