NY-ESO-1-redirected T Cells in Patients With Advanced Melanoma and Sarcoma

NCT06889766 | Recruiting Phase 1 DMC

• 1 other identifier: CHUV-DO-0026-NYESO1-2023
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief Summary

A single center, Phase I clinical trial to demonstrate safety and efficacy of LauT-1, autologous "New York Esophageal Squamous Cell Carcinoma-1 T-Cell Receptor (NY-ESO-1 TCR)-directed T cells in combination with non-myeloablative (NMA) lymphodepleting chemotherapy and low dose irradiation (LDI) in patients with NY-ESO-1 positive sarcoma and melanoma.

Conditions

Advanced Melanoma; Melanoma Metastatic; Sarcoma

Keywords

NY-ESO-1; LauT-1; TCR redirected T cell; metastatic melanoma; Sarcoma; autolog T-cell

Outcome Measures

Primary Outcomes (2)

• Safety as measured by the incidence of treatment emergent adverse events

  Safety of LauT-1 plus LDI after lymphodepleting chemotherapy will be established by classifying the observed toxicities by the MedDRA system and grading them using the National Cancer Institute (NCI) Common Toxicity Criteria (CTCAE Version 5.0) or American Society for Transplantation and Cellular Therapy (ASTCT) Cytokine Release Syndrom (CRS) consensus grading, as applicable.

  90 days

• Feasibility as measured by the rates of production failure and drop-outs before infusion

  Feasibility of LauT-1 production and administration will be evaluated as the number of cases for whom production of LauT-1 was successful (product was released based on specification criteria), and number of patients who receive LauT-1 at the intended dose according to the assigned dose-level, among all registered patients

  From start of LauT-1 production to treatment at 3 weeks

Secondary Outcomes (5)

• Long term safety as measured by the incidence of TEAE

  24 months

• 2. Objective response rate (ORR)

  90 days for each patient

• Disease control rate (DCR)

  2 years

• Progression-free survival (PFS)

  24 months

• Overall survival (OS)

  24 months

Study Arms (1)

Single arm study

OTHER

Biological: NY-ESO-1 TCR redirected autologous T cell product; Radiation: Low-dose irradiation; Drug: Non-myeloablative lymphodepleting chemotherapy

Interventions

NY-ESO-1 TCR redirected autologous T cell product BIOLOGICAL

Ex vivo expanded autologous CD4+/CD8+ cells expressing the transgenic TCR I53F recognizing NY-ESO-1 peptides presented on tumor cells in the context of HLA-A\*02. The LauT-1-ACT infusion contains a minimum of 3x10\^8 transduced cells (i.e. CD3+vβ13.1+) and a maximum of 1x10\^10 total cells.

Also known as: LauT-1

Single arm study

Low-dose irradiation RADIATION

1Gy will be administered using tomotherapy (Accuray) to all irradiable lesions.

Single arm study

Non-myeloablative lymphodepleting chemotherapy DRUG

Fludarabine (30 mg/m2 x 4 days, from D-6 to D-3) and cyclophosphamide (2400 mg/ m2 x 2 days, on days -6 and -5) are administered as an IV infusion. The cyclophosphamide dose may be reduced to 1800mg/m2 on days -6 and -5, if the patient has previously been exposed to significant cumulative doses of chemotherapy)

Single arm study

Eligibility Criteria

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

You may qualify if:

• \) Immunohistochemically documented NY-ESO-1 expression, defined as ≥ 1+ expression on either archival or fresh tumor tissue by immunohistochemistry, in ≥50% of the sampled tumor tissue.
• Patients with sarcoma, who have received at least one line of standard therapy (if available) and failed to respond, progressed or were intolerant to that therapy, will be eligible. If the participant refuses or is, in the opinion of the investigator, ineligible for these treatments, the reason must be documented in the medical record.
• Patients with metastatic melanoma:
• Without proto-oncogene B-Raf (BRAF) mutation who have received at least one line of standard therapy and failed to respond, progressed or were intolerant to that therapy, will be eligible. If the participant refuses or is, in the opinion of the investigator, ineligible for these treatments, the reason must be documented in the medical record.
• With BRAF mutation who have received at least two lines of standard therapy and failed to respond, progressed or were intolerant to that therapy, will be eligible. If the participant refuses or is, in the opinion of the investigator, ineligible for these treatments, the reason must be documented in the medical record.
• Patient must be HLA-A\*0201 and/or HLA-A\*0205 positive, as identified by high-resolution genomic deoxyribonucleic acid (DNA) typing of the HLA-A locus.
• Age ≥ 18 years
• Able to undergo apheresis
• At least one lesion accessible to biopsy for translational research (TR) at D30, without putting the patient at unusual risk.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Life expectancy of greater than 12 weeks.
• Radiologically measurable disease (as per RECIST v1.1).
• Adequate organ function

You may not qualify if:

• Patients with an active second malignancy
• Patients with symptomatic and/or untreated brain metastases, as well as leptomeningeal carcinomatosis. Patients with definitively treated brain metastases will be considered for enrolment after agreement with the Principal Investigator, as long as lesions are stable, there are no new brain lesions, and the patient does not require chronic corticosteroid treatment.
• History of idiopathic pulmonary fibrosis or evidence of active pneumonitis (any origin). History of radiation pneumonitis in the radiation field (fibrosis) is allowed.
• History of recent myocardial infarction, or unstable angina, within six months prior to enrolment
• Patients with prior allogeneic stem cell transplantation or organ transplantation
• Active severe systemic infections within 2 weeks prior to apheresis
• Patient requiring regular systemic immunosuppressive therapy. All immunosuppressive medications including but not limited to steroids, mycophenolate mofetil, azathioprine, methotrexate, thalidomide, and anti-Tumor Necrosis Factor-alpha (TNF-alpha) agents must have been discontinued at least 2 weeks before apheresis .
• History of severe immediate hypersensitivity reaction to any of the agents/ excipients of the study products.
• Women who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.
• Subjects, for whom there are concerns that they will not reliably comply with the requirements for contraception, should not be enrolled into the study.
• Any serious underlying medical condition that could interfere with study medication and potential adverse events.

Sponsors & Collaborators

• Centre Hospitalier Universitaire Vaudois: lead

Study Sites (2)

Centre Hospitalier Universitaire Vaudois (CHUV)

Lausanne, Canton of Vaud, 1011, Switzerland

NOT YET RECRUITING

Centre Hospitalier Universitaire Vaudois

Lausanne, Canton of Vaud, 1011, Switzerland

RECRUITING

MeSH Terms

Conditions

Sarcoma; Melanoma

Interventions

Radiation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Physical Phenomena

Central Study Contacts

Bernhard Gentner, MD

CONTACT

+4179 556 90 20; Bernhard.Gentner@chuv.ch

Virginie Zimmer, Study Coordinator

CONTACT

+41 21 314 97 09; virginie.zimmer@chuv.ch

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Immuno-Oncology

Model Details: This study is a single center, Phase I, feasibility and safety trial without comparative arms, enrolling up to 9 patients in 2 dose cohorts. The safety run-in cohort will follow a 3+3 algorithm. The first 3 patients will be recruited sequentially and receive a target dose of 2x10\^9 total cells (cohort 1), or a minimum of 3x10\^8 NY-ESO-1 I53F transduced T cells (LauT-1). In the absence of treatment-limiting toxicity in the safety cohort, then up to 6 additional patients will receive the maximum number of LauT-1 product resulting from the manufacturing run, with an upper limit of 1x10\^10 total cells.

Study Record Dates

• First Submitted: March 17, 2025
• First Posted: March 21, 2025
• Study Start: March 24, 2025
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2029
• Last Updated: April 20, 2025

Record last verified: 2025-04

Locations

CH (2)