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

NCT05296564 | Recruiting Phase 1

• 1 other identifier: 0752-20-HMO
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Sarcoma, Synovial; Sarcoma,Soft Tissue; Melanoma Stage IV; Triple Negative Breast Cancer; Metastatic Cancer; Non Small Cell Lung Cancer; Bladder Urothelial Carcinoma; Neuroblastoma, Metastatic; Ovary Cancer

Keywords

NY-ESO-1; TCR; adoptive transfer; retroviral transduction

Outcome Measures

Primary Outcomes (2)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  Adverse events that occur following engineered T cell transfer

  5 years

• objective tumor regression

  change in index lesions' size

  5 years

Secondary Outcomes (1)

• immune monitoring for transferred cells persistence

  5 years

Study Arms (1)

HBI 0201-ESO TCRT (Anti-NY-ESO-1 TCR-transduced peripheral blood lymphocytes)

EXPERIMENTAL

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; Drug: Cyclophosphamide; Biological: HBI 0201-ESO TCRT; Drug: Aldesleukin

Interventions

CYCLOPHOSPHAMIDE and FLUDARABIN DRUG

1\. CYCLOPHOSPHAMIDE 250 mg/msq, Day -5,-4,-3 with FLUDARABIN 25 mg/msq, Day -5,-4,-3

Also known as: CYTOXAN

HBI 0201-ESO TCRT (Anti-NY-ESO-1 TCR-transduced peripheral blood lymphocytes)

Cyclophosphamide DRUG

CYCLOPHOSPHAMIDE 250 mg/msq, Day -6, -5,-4,-3

Also known as: CYTOXAN

HBI 0201-ESO TCRT (Anti-NY-ESO-1 TCR-transduced peripheral blood lymphocytes)

HBI 0201-ESO TCRT BIOLOGICAL

HBI 0201-ESO TCRT will be infused on Day 0, after lymphodepletion. Three dose levels will be evaluated: 1x10E9, 5x10E9 and 1x10E10.

HBI 0201-ESO TCRT (Anti-NY-ESO-1 TCR-transduced peripheral blood lymphocytes)

Aldesleukin DRUG

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.

Also known as: Interleukin-2

HBI 0201-ESO TCRT (Anti-NY-ESO-1 TCR-transduced peripheral blood lymphocytes)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have histologically or cytologically confirmed diagnosis of neoplasia
• 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.
• 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.
• 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.
• 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.
• 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).
• Age ≥ 18 years and ≤ 70 years.
• Patient is able to understand and willing to sign a written informed consent.
• Clinical performance status of ECOG 0, 1 or 2.
• HLA-A\*0201or A\*0206 positive.
• 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.
• Women of child-bearing potential must have a negative pregnancy test.
• 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.
• Hematology
• ANC \> 1500/mm3 without the support of filgrastim

You may not qualify if:

• Women of child-bearing potential who are pregnant or breastfeeding.
• Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
• Active systemic infections requiring anti-infective treatment, coagulation disorders, or any other active or uncompensated major medical illnesses
• 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.
• History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, or aldesleukin.
• Subjects with a history of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within 3 months.
• Subjects unable to maintain normal oxygen saturation level in room air.
• 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).
• 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).
• LVEF ≤ 40%
• 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.

Sponsors & Collaborators

• Hadassah Medical Organization: lead

Study Sites (1)

Hadassah Medical Organization

Jerusalem, 9112001, Israel

RECRUITING

MeSH Terms

Conditions

Sarcoma, Synovial; Sarcoma; Melanoma; Triple Negative Breast Neoplasms; Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung; Neuroblastoma; Ovarian Neoplasms

Interventions

Cyclophosphamide; aldesleukin; Interleukin-2

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Breast Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neoplasms, Glandular and Epithelial; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

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

Study Officials

• Michal Lotem, MD

  Hadassah Medical Organization

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michal Lotem, Prof.

CONTACT

+972058573528; mlotem@hadassah.org.il

Yafit Halutsi

CONTACT

+972526906339; yafitha@hadassah.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: February 22, 2022
• First Posted: March 25, 2022
• Study Start: April 1, 2022
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: October 2, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)