Trial Title:
TIL Therapy Combined With Pembrolizumab for Advanced or Metastatic Refractory Stomach and Esophageal Cancer
NCT ID:
NCT06532799
Condition:
Stomach Cancer
Stomach Cancer Recurrent
Stomach Cancer, Adenocarcinoma
Esophageal Cancer
Esophageal Cancer Metastatic to Bone
Esophageal Cancer Metastatic to Lung
Esophageal Cancer Metastatic to Liver
Conditions: Official terms:
Esophageal Neoplasms
Neoplasms
Stomach Neoplasms
Cyclophosphamide
Pembrolizumab
Fludarabine
Interleukin-2
Conditions: Keywords:
CAR-T Cell Therapy
CAR-T
Tumor Infiltrating Lymphocytes
Advanced or Metastatic Refractory
Immunotherapy
TIL
Biological Therapy
Pembrolizumab
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Tumor Infiltrating Lymphocytes (TIL)
Description:
Tumor Infiltrating Lymphocytes (TIL) IV
Arm group label:
Biological Tumor Infiltrating Lymphocytes (TIL) Therapy with Immunotherapy
Intervention type:
Drug
Intervention name:
Cyclophosphamid
Description:
Cyclophosphamide will be administered as an intravenous (IV) infusion for two days.
Arm group label:
Biological Tumor Infiltrating Lymphocytes (TIL) Therapy with Immunotherapy
Intervention type:
Drug
Intervention name:
Fludarabine
Description:
Fludarabine will be administered as an intravenous (IV) infusion for five days.
Arm group label:
Biological Tumor Infiltrating Lymphocytes (TIL) Therapy with Immunotherapy
Intervention type:
Drug
Intervention name:
Interleukin-2
Description:
After TIL infusion, IL-2 will be started as a bolus administration every eight hours, for
a maximum of eight doses.
Arm group label:
Biological Tumor Infiltrating Lymphocytes (TIL) Therapy with Immunotherapy
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
Intravenous (IV) infusion
Arm group label:
Biological Tumor Infiltrating Lymphocytes (TIL) Therapy with Immunotherapy
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. 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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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
- 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.
Exclusion Criteria:
- 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.
- 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.
Gender:
All
Minimum age:
16 Years
Maximum age:
90 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
District One Hospital
Address:
City:
Beijing
Zip:
086-373
Country:
China
Status:
Recruiting
Contact:
Last name:
SAMI XI, dr
Phone:
+14012275001
Email:
SFM@districtonehospital.com
Start date:
September 10, 2024
Completion date:
December 28, 2026
Lead sponsor:
Agency:
Essen Biotech
Agency class:
Other
Source:
Essen Biotech
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06532799
