Phase I study to evaluate the safety and feasibility of an immunotherapy based on genetically modified autologous T lymphocytes to specifically recognize the tumor antigen NY-ESO-1 in patients with advanced melanoma or sarcoma.

Switzerland (ICTRP)

ID di studio ICTRP
NCT06889766 (ICTRP)

Titolo ufficiale (approvato dal comitato etico)
A phase I study evaluating safety and feasibility of redirected autologous T cells expressing a high affinity TCR specific for NY-ESO-1 (LauT-1) in patients with advanced melanoma and sarcoma (BASEC)

Titolo accademico
A Phase I Study Evaluating Safety and Feasibility of Redirected Autologous T Cells Expressing a High Affinity TCR Specific for NY-ESO-1 (LauT-1) in Patients With Advanced Melanoma and Sarcoma (ICTRP)

Titolo pubblico
NY-ESO-1-redirected T Cells in Patients With Advanced Melanoma and Sarcoma (ICTRP)

Malattie studiate
Advanced MelanomaMelanoma MetastaticSarcoma (ICTRP)

Intervento studiato
Biological: NY-ESO-1 TCR redirected autologous T cell productRadiation: Low-dose irradiationDrug: Non-myeloablative lymphodepleting chemotherapy (ICTRP)

Tipo di studio
Interventional (ICTRP)

Disegno dello studio
Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Criteri di inclusione/esclusione
Inclusion criteria at pre-screening step-1 1) Patients with histologically confirmed
advanced or metastatic cutaneous melanoma or any type of sarcoma.

Inclusion criteria at pre-screening step-2

1) 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.

Inclusion criteria at screening

1. 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.

2. Patients with metastatic melanoma:

1. 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.

2. 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.

3. 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.

4. Age = 18 years

5. Able to undergo apheresis

6. At least one lesion accessible to biopsy for translational research (TR) at D30,
without putting the patient at unusual risk.

7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

8. Life expectancy of greater than 12 weeks.

9. Radiologically measurable disease (as per RECIST v1.1).

10. Adequate organ function

Exclusion Criteria:

1. Patients with an active second malignancy

2. 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.

3. History of idiopathic pulmonary fibrosis or evidence of active pneumonitis (any
origin). History of radiation pneumonitis in the radiation field (fibrosis) is
allowed.

4. History of recent myocardial infarction, or unstable angina, within six months prior
to enrolment

5. Patients with prior allogeneic stem cell transplantation or organ transplantation

6. Active severe systemic infections within 2 weeks prior to apheresis

7. 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 .

8. History of severe immediate hypersensitivity reaction to any of the agents/
excipients of the study products.

9. Women who are pregnant or breastfeeding because of the potentially dangerous effects
of the treatment on the fetus or infant.

10. Subjects, for whom there are concerns that they will not reliably comply with the
requirements for contraception, should not be enrolled into the study.

11. Any serious underlying medical condition that could interfere with study medication
and potential adverse events. (ICTRP)

non disponibile

Endpoint primari e secondari
Safety as measured by the incidence of treatment emergent adverse events;Feasibility as measured by the rates of production failure and drop-outs before infusion (ICTRP)

Long term safety as measured by the incidence of TEAE;2. Objective response rate (ORR);Disease control rate (DCR);Progression-free survival (PFS);Overall survival (OS) (ICTRP)

Data di registrazione
non disponibile

Inclusione del primo partecipante
non disponibile

Sponsor secondari
non disponibile

Contatti aggiuntivi
Bernhard Gentner, MDBernhard Gentner, MD, Bernhard.Gentner@chuv.chBernhard.Gentner@chuv.ch, +4179 556 90 20+41 79 556 90 20 (ICTRP)

ID secondari
CHUV-DO-0026-NYESO1-2023 (ICTRP)

Risultati-Dati individuali dei partecipanti
non disponibile

Ulteriori informazioni sullo studio
https://clinicaltrials.gov/ct2/show/NCT06889766 (ICTRP)