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

Adult Solid Neoplasm Clinical Trial

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

Status Completed

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Adult Solid Neoplasm
• Childhood Solid Neoplasm
• Metastatic Neoplasm
• Neoplasm Metastasis
• Neoplasms

• NCT number: NCT02775292
• Study type: Interventional
• Source: Jonsson Comprehensive Cancer Center
• Status: Completed
• Phase: Phase 1
• Start date: January 3, 2017
• Completion date: April 8, 2019