Stomach CancerPhase 1/2BAH250NCT06532799
TIL Therapy Combined With Pembrolizumab for Advanced or Metastatic Refractory Stomach and Esophageal Cancer
A Phase 1/2 study testing Tumor Infiltrating Lymphocytes (TIL), Cyclophosphamid and Fludarabine in people with Stomach Cancer and Stomach Cancer Recurrent, run by Essen Biotech at 1 site in China.
Trial summary
This Phase I/II study evaluates the safety and efficacy of autologous tumor-infiltrating lymphocytes (TIL) therapy combined with Pembrolizumab (Keytruda) immunotherapy in patients with advanced or metastatic refractory stomach and esophageal cancer. Read more about this study
- Who is it for?
- Ages 16 to 90 years
- Conditions the study is for
- Stomach Cancer, Stomach Cancer Recurrent, Stomach Cancer, Adenocarcinoma
- What is being tested?
- Tumor Infiltrating Lymphocytes (TIL), Cyclophosphamid and Fludarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 1 siteChina
- Study dates
- 10 Sep 2024to 28 Dec 2026
- Phase
- Phase 1/2
- 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 16 to 90 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age: 16 years to 90 years
- Histologically diagnosed as primary/relapsed/metastasized Cancer
- Expected life span more than 3 months
- Karnofsky≥60% or ECOG score 0-2
- Test subjects have failed standard treatment regimens, or there are no standard treatment regimens available.
- Test subjects must have tumor regions eligible for biopsy or resection, or malignant body fluid where TILs can be isolated
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- At least 1 evaluable tumor lesion
- Hematology and Chemistry（within 7 days prior to enrollment）:
- Absolute count of white blood cells≥2.5×10^9/L
- Absolute count of neutropils≥1.5×10^9/L
- Absolute count of lymphocytes ≥0.7×109/L
- Platelet count≥100×10^9
- hemoglobin≥90 g/L
- Activated partial thromboplastin time (APTT) ≤1.5xULN (Unless received anticoagulant therapy within the previous 3 days)
- International normalized ratio (INR) ≤1.5xULN (Unless received anticoagulant therapy within the previous 3 days)
- Serum creatinine ≤1.5mg/dL(or ≤132.6μmol/L), or clearance rate≥50mL/min
- Serum ALT/AST ≤3×ULN(subjects with liver metastasis ≤3×ULN)
- Totol bilirubin≤1.5×ULN
- No absolute or relative contraindications to operation or biopsy
- Test subjects with child-bearing potential must be willing to practice approved highly effective methods of contraception at the time of informed consent and continue within 1 year after the completion of lymphodepletion
- Any malignant tumor-targeting therapies, including radiotherapy, chemotherapy, and biologics must cease 28 days before obtaining TILs
- Be able to understand and sign the informed consent document;
- Be able to stick to the follow-up visit plan and other requirements in the agreement.
Who cannot join
- Need glucocorticoid treatment, and daily dose of Prednisone greater than 15mg (or equivalent doses of hormones) or outoimmune diseases requiring immunomodulatory treatment
- Forced expiratory volume in one second (FEV1) less than 2L, diffusing capacity of the lung for carbon monoxide (DLCO) (calibrated) less than 40%
- Significant cardiovascular anomalies according to any of the following definitions:
- New York Heart Association (NYHA) Grade III or IV congestive heart failure, clinically significant
- Low blood pressure, uncontrollable symptomatic coronary artery diseases, or ejection fraction less than 35%; Severe cardiac rhythm and conduction anomaly, such as ventricular arrhythmia requiring clinical intervention, second-third degree atrioventricular conductive block, etc.
- Human immunodeficiency virus (HIV) infection or anti-HIV antibody positive, active HBV or HCV infection (HBsAg positive and/or anti-HCV positive), syphilis infection or Treponema pallidum antibody positive.
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- Severe physical or mental diseases;
- Have a systemic active infection requiring treatment, or have positive blood cultures(or imaging evidence of infection).
- Having been treated within a month or being treated now with other medicines, or other biologic therapy, chemo-or radiotherapy.
- History of allergy to chemical compounds consisting of chemical and biological substances resembling cell therapy.
- Having received immunotherapy and developed an irAE level greater than Level 3.
- Previous anti-tumor treatment AE did not return to CTCAE5.0 version grade 1 or below (toxicity considered by the investigator as non-safety concerns like alopecia excluded).
- Females in pregnancy or lactation. History of organ transplantation, allogeneic stem cell transplantation, and renal replacement therapy.
- Researchers consider the test subject as having a history of other severe systemic diseases, or other reasons inappropriate for the clinical study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
District One Hospital
Beijing, Beijing Municipality, 086-373
SAMI XI, dr, +14012275001, SFM@districtonehospital.com
About this study
Official title: Efficacy and Safety of Autologous Tumor-Infiltrating Lymphocytes (TIL) Therapy Combined With Pembrolizumab (Keytruda) Immunotherapy in Patients With Advanced or Metastatic Refractory Stomach and Esophageal Cancer
This Phase I/II study evaluates the safety and efficacy of autologous tumor-infiltrating lymphocytes (TIL) therapy combined with Pembrolizumab (Keytruda) immunotherapy in patients with advanced or metastatic refractory stomach and esophageal cancer. Lifileucel (Amtagvi), the first FDA-approved TIL therapy, has shown significant promise in treating unresectable or metastatic melanoma by leveraging the patient's own immune cells to target and destroy cancer cells. This study aims to apply a similar approach to stomach and esophageal cancers. TILs will be harvested from patients' tumors, expanded in vitro, and infused back into the patients following a non-myeloablative lymphodepletion regimen. Pembrolizumab, a monoclonal antibody that targets the PD-1 receptor on T cells, will be administered to enhance the immune response. The primary endpoint is to determine the objective response rate (ORR) of this combined therapy. Secondary endpoints include disease control rate (DCR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), and quality of life (QoL). This trial aims to provide a novel, personalized treatment option for patients with limited therapeutic alternatives.
Read the detailed description
Tumor-infiltrating lymphocytes (TILs) therapy is an advanced form of adoptive cell therapy that harnesses the patient's immune cells to fight cancer. Lifileucel (Amtagvi), the first FDA-approved TIL therapy, has demonstrated substantial efficacy in treating unresectable or metastatic melanoma. By extracting lymphocytes from the patient's tumor, expanding them ex vivo, and reinfusing them, Lifileucel has shown to significantly enhance the immune system's ability to target and destroy cancer cells. This promising approach serves as the foundation for the current study, aiming to apply a similar methodology to advanced or metastatic refractory stomach and esophageal cancers, which typically have poor prognoses and limited treatment options.
This trial involves a multi-step treatment process. First, tumor samples are collected from patients for TIL extraction. Following this, a lymphodepletion regimen using cyclophosphamide and fludarabine is administered to prepare the body for the infusion of expanded autologous TILs. After the TIL infusion, Aldesleukin (IL-2) is given to stimulate the TILs' activity. Pembrolizumab (Keytruda), an immunotherapy that targets the PD-1 receptor on T cells, is also administered to further enhance the immune response against the tumor.
The primary goal of this trial is to determine the objective response rate (ORR) of this combined therapy. Secondary endpoints include the disease control rate (DCR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), and changes in the quality of life (QoL) of patients.
Patients will be closely monitored for side effects and reactions during their hospital stay and throughout the follow-up period. Safety will be assessed based on the incidence and severity of adverse events, while efficacy will be evaluated using RECIST v1.1 criteria. By leveraging the patient's own immune cells and combining them with advanced immunotherapies, this trial aims to provide a novel, personalized treatment option for patients with advanced or metastatic refractory stomach and esophageal cancer, building on the success observed with Lifileucel (Amtagvi) in melanoma treatment.
- Conditions
- Stomach Cancer, Stomach Cancer Recurrent, Stomach Cancer, Adenocarcinoma, Esophageal Cancer, Esophageal Cancer Metastatic to Bone, Esophageal Cancer Metastatic to Lung
- Being tested
- Tumor Infiltrating Lymphocytes (TIL), Cyclophosphamid, Fludarabine, Interleukin-2, Pembrolizumab
- Keywords
- CAR-T Cell Therapy, CAR-T, Tumor Infiltrating Lymphocytes, Advanced or Metastatic Refractory, Immunotherapy, TIL, Biological Therapy, Pembrolizumab
- Medical subject headings
- Stomach Neoplasms, Adenocarcinoma, Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tumor Infiltrating Lymphocytes (TIL)Biological
Tumor Infiltrating Lymphocytes (TIL) IV
CyclophosphamidDrug
Cyclophosphamide will be administered as an intravenous (IV) infusion for two days.
FludarabineDrug
Fludarabine will be administered as an intravenous (IV) infusion for five days.
Interleukin-2Drug
After TIL infusion, IL-2 will be started as a bolus administration every eight hours, for a maximum of eight doses.
PembrolizumabDrug
Intravenous (IV) infusion
| Study group | Role | What they receive |
|---|---|---|
| Biological Tumor Infiltrating Lymphocytes (TIL) Therapy with Immunotherapy | Experimental | Patients receive pembrolizumab IV on day -14, cyclophosphamide IV QD on days -7 to -6, fludarabine IV over 30 minutes QD on days -5 to -1, and TILs IV infusion on day 0. Patients also receive pembrolizumab IV on day 28 and 70, and undergo surgery on day 80.
MAINTENANCE: Patients receive pembrolizumab IV every 6 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Receives: Biological: Tumor Infiltrating Lymphocytes (TIL); Drug: Cyclophosphamid; Drug: Fludarabine; Drug: Interleukin-2; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events
To characterize the safety profile of (TIL) and natural autologous TIL in patients with advanced solid tumors who were failed to standard treatment as assessed by incidence of adverse events.
Measured: 6 months
Secondary outcomes (4)
Objective Response Rate (ORR)
Proportion of patients with response per Response Evaluation Criteria in Solid Tumors
Measured: Up to 36 months
Disease Control Rate (DCR）
Percentage of patients that meet CR, PR and SD criteria set in this study
Measured: Up to 36 months
Duration of Response (DOR)
The time length between the first confirmed objective response to the treatment and the subsequent disease progression
Measured: Up to 36 months
Progression-Free Survival (PFS)
The time length between TIL infusion and confirmed subsequent disease progression
Measured: Up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2024
- Study start10 Sep 2024
- Primary completion15 Dec 2025 (estimated)
- Study completion28 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stomach CancerStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 75 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Essen Biotech
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06532799
- Sponsor's protocol ID
- ESBI202471
- Acronym
- BAH250
- Status last verified
- Nov 2024
- First submitted
- 29 Jul 2024
- Last updated
- 12 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Autologous Tumor-Infiltrating Lymphocytes (TIL) Therapy Combined With Pembrolizumab (Keytruda) Immunotherapy in Patients With Advanced or Metastatic Refractory Stomach and Esophageal Cancer
- ClinicalTrials.gov ID
- NCT06532799
- Acronym / sponsor ID
- BAH250 / ESBI202471
- Conditions
- Stomach Cancer, Stomach Cancer Recurrent, Stomach Cancer, Adenocarcinoma, Esophageal Cancer, Esophageal Cancer Metastatic to Bone, Esophageal Cancer Metastatic to Lung
- Keywords
- CAR-T Cell Therapy, CAR-T, Tumor Infiltrating Lymphocytes, Advanced or Metastatic Refractory, Immunotherapy, TIL, Biological Therapy, Pembrolizumab
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- Essen BiotechUniversity, hospital or other
- Study start
- 10 Sep 2024 (actual)
- Primary completion
- 15 Dec 2025 (estimated)
- Study completion
- 28 Dec 2026 (estimated)
- First posted
- 1 Aug 2024 (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.
This Phase I/II study evaluates the safety and efficacy of autologous tumor-infiltrating lymphocytes (TIL) therapy combined with Pembrolizumab (Keytruda) immunotherapy in patients with advanced or metastatic refractory stomach and esophageal cancer. Lifileucel (Amtagvi), the first FDA-approved TIL therapy, has shown significant promise in treating unresectable or metastatic melanoma by leveraging the patient's own immune cells to target and destroy cancer cells. This study aims to apply a similar approach to stomach and esophageal cancers. TILs will be harvested from patients' tumors, expanded in vitro, and infused back into the patients following a non-myeloablative lymphodepletion regimen. Pembrolizumab, a monoclonal antibody that targets the PD-1 receptor on T cells, will be administered to enhance the immune response. The primary endpoint is to determine the objective response rate (ORR) of this combined therapy. Secondary endpoints include disease control rate (DCR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), and quality of life (QoL). This trial aims to provide a novel, personalized treatment option for patients with limited therapeutic alternatives.
Detailed description
Tumor-infiltrating lymphocytes (TILs) therapy is an advanced form of adoptive cell therapy that harnesses the patient's immune cells to fight cancer. Lifileucel (Amtagvi), the first FDA-approved TIL therapy, has demonstrated substantial efficacy in treating unresectable or metastatic melanoma. By extracting lymphocytes from the patient's tumor, expanding them ex vivo, and reinfusing them, Lifileucel has shown to significantly enhance the immune system's ability to target and destroy cancer cells. This promising approach serves as the foundation for the current study, aiming to apply a similar methodology to advanced or metastatic refractory stomach and esophageal cancers, which typically have poor prognoses and limited treatment options.
This trial involves a multi-step treatment process. First, tumor samples are collected from patients for TIL extraction. Following this, a lymphodepletion regimen using cyclophosphamide and fludarabine is administered to prepare the body for the infusion of expanded autologous TILs. After the TIL infusion, Aldesleukin (IL-2) is given to stimulate the TILs' activity. Pembrolizumab (Keytruda), an immunotherapy that targets the PD-1 receptor on T cells, is also administered to further enhance the immune response against the tumor.
The primary goal of this trial is to determine the objective response rate (ORR) of this combined therapy. Secondary endpoints include the disease control rate (DCR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), and changes in the quality of life (QoL) of patients.
Patients will be closely monitored for side effects and reactions during their hospital stay and throughout the follow-up period. Safety will be assessed based on the incidence and severity of adverse events, while efficacy will be evaluated using RECIST v1.1 criteria. By leveraging the patient's own immune cells and combining them with advanced immunotherapies, this trial aims to provide a novel, personalized treatment option for patients with advanced or metastatic refractory stomach and esophageal cancer, building on the success observed with Lifileucel (Amtagvi) in melanoma treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Biological Tumor Infiltrating Lymphocytes (TIL) Therapy with Immunotherapy | Experimental | Biological: Tumor Infiltrating Lymphocytes (TIL), Drug: Cyclophosphamid, Drug: Fludarabine, Drug: Interleukin-2, Drug: PembrolizumabPatients receive pembrolizumab IV on day -14, cyclophosphamide IV QD on days -7 to -6, fludarabine IV over 30 minutes QD on days -5 to -1, and TILs IV infusion on day 0. Patients also receive pembrolizumab IV on day 28 and 70, and undergo surgery on day 80. MAINTENANCE: Patients receive pembrolizumab IV every 6 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 16 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (23 listed)
- Age: 16 years to 90 years
- Histologically diagnosed as primary/relapsed/metastasized Cancer
- Expected life span more than 3 months
- Karnofsky≥60% or ECOG score 0-2
- Test subjects have failed standard treatment regimens, or there are no standard treatment regimens available.
Key exclusion criteria (14 listed)
- Need glucocorticoid treatment, and daily dose of Prednisone greater than 15mg (or equivalent doses of hormones) or outoimmune diseases requiring immunomodulatory treatment
- Forced expiratory volume in one second (FEV1) less than 2L, diffusing capacity of the lung for carbon monoxide (DLCO) (calibrated) less than 40%
- Significant cardiovascular anomalies according to any of the following definitions:
- New York Heart Association (NYHA) Grade III or IV congestive heart failure, clinically significant
- Low blood pressure, uncontrollable symptomatic coronary artery diseases, or ejection fraction less than 35%; Severe cardiac rhythm and conduction anomaly, such as ventricular arrhythmia requiring clinical intervention, second-third degree atrioventricular conductive block, 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 |
|---|---|---|
| Tumor Infiltrating Lymphocytes (TIL)Tumor Infiltrating Lymphocytes (TIL) IV | Biological | Biological Tumor Infiltrating Lymphocytes (TIL) Therapy with Immunotherapy |
| CyclophosphamidCyclophosphamide will be administered as an intravenous (IV) infusion for two days. | Drug | Biological Tumor Infiltrating Lymphocytes (TIL) Therapy with Immunotherapy |
| FludarabineFludarabine will be administered as an intravenous (IV) infusion for five days. | Drug | Biological Tumor Infiltrating Lymphocytes (TIL) Therapy with Immunotherapy |
| Interleukin-2After TIL infusion, IL-2 will be started as a bolus administration every eight hours, for a maximum of eight doses. | Drug | Biological Tumor Infiltrating Lymphocytes (TIL) Therapy with Immunotherapy |
| PembrolizumabIntravenous (IV) infusion | Drug | Biological Tumor Infiltrating Lymphocytes (TIL) Therapy with Immunotherapy |
Primary outcome
Adverse Events
Time frame: 6 months
To characterize the safety profile of (TIL) and natural autologous TIL in patients with advanced solid tumors who were failed to standard treatment as assessed by incidence of adverse events.
4 secondary outcomes
Objective Response Rate (ORR)
Time frame: Up to 36 months
Disease Control Rate (DCR）
Time frame: Up to 36 months
Duration of Response (DOR)
Time frame: Up to 36 months
Progression-Free Survival (PFS)
Time frame: Up to 36 months
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 12 Nov 2024.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Tumor Infiltrating Lymphocytes (TIL), Cyclophosphamid and Fludarabine in people with Stomach Cancer and Stomach Cancer Recurrent, run by Essen Biotech at 1 site in China.
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 23 inclusion and 14 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 12 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Rhoda M Smith, Phd (+12077706670, clinical-trials@essen-biotech.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse Events (time frame: 6 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 12 Nov 2024.