TIL Therapy Combined With Pembrolizumab for Advanced or Metastatic Refractory Stomach and Esophageal Cancer

NCT06532799 | Recruiting Phase 1 DMC

• 1 other identifier: ESBI202471
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

CAR-T Cell Therapy; CAR-T; Tumor Infiltrating Lymphocytes; Advanced or Metastatic Refractory; Immunotherapy; TIL; Biological Therapy; Pembrolizumab

Outcome Measures

Primary Outcomes (1)

• 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.

  6 months

Secondary Outcomes (4)

• Objective Response Rate (ORR)

  Up to 36 months

• Disease Control Rate (DCR）

  Up to 36 months

• Duration of Response (DOR)

  Up to 36 months

• Progression-Free Survival (PFS)

  Up to 36 months

Study Arms (1)

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.

Biological: Tumor Infiltrating Lymphocytes (TIL); Drug: Cyclophosphamid; Drug: Fludarabine; Drug: Interleukin-2; Drug: Pembrolizumab

Interventions

Tumor Infiltrating Lymphocytes (TIL) BIOLOGICAL

Tumor Infiltrating Lymphocytes (TIL) IV

Biological Tumor Infiltrating Lymphocytes (TIL) Therapy with Immunotherapy

Cyclophosphamid DRUG

Cyclophosphamide will be administered as an intravenous (IV) infusion for two days.

Biological Tumor Infiltrating Lymphocytes (TIL) Therapy with Immunotherapy

Fludarabine DRUG

Fludarabine will be administered as an intravenous (IV) infusion for five days.

Biological Tumor Infiltrating Lymphocytes (TIL) Therapy with Immunotherapy

Interleukin-2 DRUG

After TIL infusion, IL-2 will be started as a bolus administration every eight hours, for a maximum of eight doses.

Biological Tumor Infiltrating Lymphocytes (TIL) Therapy with Immunotherapy

Pembrolizumab DRUG

Intravenous (IV) infusion

Biological Tumor Infiltrating Lymphocytes (TIL) Therapy with Immunotherapy

Eligibility Criteria

• Age: 16 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Essen Biotech: lead

Study Sites (1)

District One Hospital

Beijing, Beijing Municipality, 086-373, China

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms; Adenocarcinoma; Esophageal Neoplasms

Interventions

Cyclophosphamide; fludarabine; Interleukin-2; pembrolizumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Esophageal Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Central Study Contacts

Rhoda M Smith, Phd

CONTACT

+12077706670; clinical-trials@essen-biotech.com

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: July 29, 2024
• First Posted: August 1, 2024
• Study Start: September 10, 2024
• Primary Completion: December 15, 2025
• Study Completion (Estimated): December 28, 2026
• Last Updated: November 12, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)