Anti-NY-ESO-1 TCR-Gene Engineered Lymphocytes Given by Infusion to Patients With NY-ESO-1 -Expressing Metastatic Cancers

September 29, 2025 updated by: Hadassah Medical Organization

A Phase I/II Dose Escalation, Safety and Efficacy Study of Anti-NY-ESO-1 T Cell Receptor (TCR)-Gene Engineered Lymphocytes Given by Infusion to Patients With NY-ESO-1 -Expressing Metastatic Cancers

A Phase I/II Dose Escalation, Safety and Efficacy Study of HBI 0201-ESO TCRT (anti-NY-ESO-1 TCR-Gene Engineered Lymphocytes) Given by Infusion to Patients with NY-ESO-1 -Expressing Metastatic Cancers

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a two-part, non-randomized, open label, single-site Phase I/II study. The first Part A is a dose ranging maximum tolerated dose (MTD) study and Part B is an extension phase to evaluate safety at the selected safe dose. A Data Safety Monitoring Board (DSMB) will determine the safe dose for testing in the expansion phase (Part B).

Part A will be according to a 3+3 dose escalation design. A total of up to 20 patients will participate in this Part.

Part B will be an expansion phase. The objective will be to determine if the treatment regimen is associated with a clinical response rate that can rule out 5% (p0=0.05) in favor of a modest 20% Partial Response (PR) + Complete Response (CR) rate (p1=0.20).

A total of up to 43 patients may be enrolled in Part B (41 +2, allowing for up to 2 non-evaluable patients).

Study Type

Interventional

Enrollment (Estimated)

3

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Israel
      • Jerusalem, Israel, 9112001
        • Recruiting
        • Hadassah Medical Organization
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Have histologically or cytologically confirmed diagnosis of neoplasia
  2. Measurable (per RECIST v1.1 criteria) metastatic cancer or locally advanced refractory/recurrent malignancy not amenable to curative treatment. Lesions previously irradiated may be considered measurable only if growth has been documented since local treatment completion.
  3. The tumor expresses ESO as assessed immunohistochemistry of resected tissue. To this end, archived tumor tissue suitable for analysis must be available or re-biopsy performed on study. Tissue staining must encompass more than 10% of tumor section.
  4. Patients must have previously either (1) received at least first-line or second-line standard therapy for metastatic disease, if known to be effective for that disease, and have been either non-responders (progressive disease), intolerable or have recurred or (2) Recurred within 6 months of adjuvant systemic therapy known to be active also in the metastatic setting.
  5. Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible. Patients with surgically resected brain metastases are eligible.
  6. More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients' toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).
  7. Age ≥ 18 years and ≤ 70 years.
  8. Patient is able to understand and willing to sign a written informed consent.
  9. Clinical performance status of ECOG 0, 1 or 2.
  10. HLA-A*0201or A*0206 positive.
  11. Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for four months after treatment.
  12. Women of child-bearing potential must have a negative pregnancy test.
  13. Serology: Seronegative for HIV antibody, hepatitis B antigen, and hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.

  14. Hematology

    • ANC > 1500/mm3 without the support of filgrastim
    • WBC ≥ 3000/mm3
    • Platelet count ≥ 100,000/mm3
    • Hemoglobin > 8.0 g/dL. Subjects may be transfused to reach this cut-off.

  15. Chemistry

    • Serum ALT/AST ≤ 2.5 x ULN
    • Creatinine clearance ≥40ml/min
    • Total bilirubin ≤ 1.5 mg/dL, except in patients with Gilbert's Syndrome, who must have a total bilirubin < 3.0 mg/dL.
    • INR < 1.5

Exclusion Criteria:

  1. Women of child-bearing potential who are pregnant or breastfeeding.
  2. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
  3. Active systemic infections requiring anti-infective treatment, coagulation disorders, or any other active or uncompensated major medical illnesses
  4. Concurrent systemic steroid therapy, not including replacement therapy or treatment with prednisone up to 10mg daily or its equivalent. Or any other form of immunosuppressive therapy within 7 days before the first dose of study intervention.
  5. History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, or aldesleukin.
  6. Subjects with a history of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within 3 months.
  7. Subjects unable to maintain normal oxygen saturation level in room air.

  8. Subjects who have had a venous thromboembolic event requiring anticoagulation and who meet any of the following criteria:

    • Have been on a stable dose of anticoagulation for < 1 month (except for acute line insertion induced thrombosis).
    • Have had a Grade 2, 3, or 4 hemorrhage in the last 30 days or are experiencing continued symptoms from their venous thromboembolic event (e.g. continued dyspnea or oxygen requirement).
  9. Has a known additional malignancy within the last 3 years. Exceptions include early stage cancers (carcinoma in situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy).
  10. LVEF ≤ 40%

  11. Documented FEV1 ≤ 60% predicted tested in patients with:

    • A prolonged history of cigarette smoking (≥ 20 pack-year smoking history, with cessation within the past two years).
    • Symptoms of respiratory dysfunction.
  12. Patients who are at the time of study initiation receiving any other investigational agents.
  13. Carcinomatosis meningitis or other brain involvement exceeding that allowed above.
  14. Has received live vaccine within 30 days before the first dose of study intervention. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: HBI 0201-ESO TCRT (Anti-NY-ESO-1 TCR-transduced peripheral blood lymphocytes)

This is a two-part, non-randomized, open label, single-site Phase I/II study. The first Part A is a dose ranging maximum tolerated dose (MTD) study and Part B is an extension phase to evaluate safety at the selected safe dose. A Data Safety Monitoring Board (DSMB) will determine the safe dose for testing in the expansion phase (Part B).

Part A will be according to a 3+3 dose escalation design. A total of up to 20 patients will participate in this Part.

Part B will be an expansion phase. The objective will be to determine if the treatment regimen is associated with a clinical response rate that can rule out 5% (p0=0.05) in favor of a modest 20% Partial Response (PR) + Complete Response (CR) rate (p1=0.20).

A total of up to 43 patients may be enrolled in Part B (41 +2, allowing for up to 2 non-evaluable patients).
Drug: CYCLOPHOSPHAMIDE and FLUDARABIN
1. CYCLOPHOSPHAMIDE 250 mg/msq, Day -5,-4,-3 with FLUDARABIN 25 mg/msq, Day -5,-4,-3
Other Names:
  • CYTOXAN
Drug: Cyclophosphamide
CYCLOPHOSPHAMIDE 250 mg/msq, Day -6, -5,-4,-3
Other Names:
  • CYTOXAN
Biological: HBI 0201-ESO TCRT
HBI 0201-ESO TCRT will be infused on Day 0, after lymphodepletion. Three dose levels will be evaluated: 1x10E9, 5x10E9 and 1x10E10.
Drug: Aldesleukin
Continuous infusion of aldesleukin 18x10E6 IU/24h will be given 24 hours post HBI 0201-ESO TCRT infusion, for four days or until a dose limiting toxicity will occur that mimics cytokine release syndrome (CRS) including blood pressure drop, oliguria or confusion- all of them or any one alone.
Other Names:
  • Interleukin-2

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
objective tumor regression
Time Frame: 5 years
change in index lesions' size
5 years
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame: 5 years
Adverse events that occur following engineered T cell transfer
5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
immune monitoring for transferred cells persistence
Time Frame: 5 years
blood test for ESO-TCRT cells' presence
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hadassah Medical Organization

Investigators

  • Principal Investigator: Michal Lotem, MD, Hadassah Medical Organization

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2022

Primary Completion (Estimated)

December 30, 2027

Study Completion (Estimated)

December 30, 2027

Study Registration Dates

First Submitted

February 22, 2022

First Submitted That Met QC Criteria

March 15, 2022

First Posted (Actual)

March 25, 2022

Study Record Updates

Last Update Posted (Estimated)

October 2, 2025

Last Update Submitted That Met QC Criteria

September 29, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0752-20-HMO

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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