NCT02775292

Gene-Modified T Cells, Vaccine Therapy, and Nivolumab in Treating Patients With Stage IV or Locally Advanced Solid Tumors Expressing NY-ESO-1

NY-ESO-1 TCR Engineered Adoptive Cell Transfer Therapy With Nivolumab PD-1 Blockade

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 1 (actual)
• Sponsor: Jonsson Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 16 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and the best dose of nivolumab when given together with gene-modified T cells and vaccine therapy in treating patients with solid tumors that express the cancer-testes antigen NY-ESO-1 gene AND have spread from where it started to nearby tissue or lymph nodes (locally advanced) or distant organs (stage IV). T cells are a special type of white blood cells (immune cell) that have the ability to kill cancer cells. Nivolumab may block PD-1 which is found on T cells and help the immune system kill cancer cells. Placing a modified gene for the NY-ESO-1 T cell receptor (TCR) into the patients' T cells in the laboratory and then giving them back to the patient may help the body build an immune response to kill tumor cells that express NY-ESO-1. Dendritic cells are another type of blood cell that can teach other cells in the body to look for cancer cells and attack them. Giving a dendritic cell vaccine with the NY-ESO-1 protein may help dendritic cells teach the immune system to target cancer cells expressing that protein, and further help the T cells attack cancer. Giving nivolumab together with gene-modified T-cells and dendritic cell vaccine may teach the immune system to recognize and kill cancer cells that express NY-ESO-1.

Detailed description

PRIMARY OBJECTIVES: I. To determine the safety of the addition of the PD-1 blocking monoclonal antibody, nivolumab, to NY-ESO TCR-transduced autologous peripheral blood lymphocyte (PBL) adoptive cell transfer (ACT) in a dose escalation scheme in two study cohorts at 1 mg/kg and 3 mg/kg of nivolumab intravenous (i.v.) every two weeks for up to 2 years. SECONDARY OBJECTIVES: I. To determine the feasibility of delivering the TCR transgenic cell dose and PD-1 blockade to patients. II. To determine the persistence of NY-ESO-1 TCR-engineered peripheral blood mononuclear cell (PBMC) in serial peripheral blood samples and in biopsies of accessible metastatic lesions. EXPLORATORY OBJECTIVES: I. To determine whether blocking PD-1 will maintain the antitumor functionality of adoptively transferred TCR transgenic lymphocytes. II. To explore the use of positron emission tomography (PET)-based imaging using the PET tracer (18F) fluorodeoxy-glucose (\[18F\]FDG) with the goal of determining if the adoptively transferred NY-ESO-1 TCR-engineered PBMC when administered with nivolumab home and expand in secondary lymphoid organs and tumor deposits. III. Clinical antitumor activity recording objective response rate. OUTLINE: This is a dose-escalation study of nivolumab. CONDITIONING REGIMEN: Patients receive cyclophosphamide intravenously (IV) over 1 hour on days -5 to -4 and fludarabine phosphate IV over 15-30 minutes on days -4 to -1. NY-ESO-1 TCR PBMC INFUSION: Patients receive NY-ESO-1 TCR PBMC IV on day 0. NIVOLUMAB: Patients receive nivolumab IV over 60 minutes on day 0 or 1. Treatment repeats every 2 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. NY-ESO-1(157-165) PEPTIDE PULSED DENDRITIC CELL (DC): Patients receive NY-ESO-1(157-165) peptide pulsed DC intradermally (ID) on days 1, 14, and 28. LOW DOSE ALDESLEUKIN ADMINISTRATION: Patients receive aldesleukin subcutaneously (SC) twice daily (BID) for 7 days beginning on day 1 for a maximum of 14 doses. After completion of study treatment, patients are followed up at least every 6 months for 3 years and then at least every 12 months for up to 15 years.

Conditions

• Adult Solid Neoplasm
• Childhood Solid Neoplasm
• Metastatic Neoplasm

Interventions

Type	Name	Description
BIOLOGICAL	Aldesleukin	Given SC
DRUG	Cyclophosphamide	Given IV
DRUG	Fludarabine Phosphate	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
BIOLOGICAL	Nivolumab	Given IV
BIOLOGICAL	NY-ESO-1 Reactive TCR Retroviral Vector Transduced Autologous PBL	Given IV
BIOLOGICAL	NY-ESO-1(157-165) Peptide-pulsed Autologous Dendritic Cell Vaccine	Given ID
PROCEDURE	Positron Emission Tomography	Correlative studies

Timeline

• Start date: 2017-01-03
• Primary completion: 2019-04-08
• Completion: 2019-04-08
• First posted: 2016-05-17
• Last updated: 2025-07-30

Locations

1 site across 1 country: United States