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

NCT02775292 | Completed Phase 1 DMC

• 4 other identifiers: 15-001433NCI-2016-00201R35CA197633K12HD000850
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Adult Solid Neoplasm; Childhood Solid Neoplasm; Metastatic Neoplasm

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events, defined following the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

  Simple descriptive statistics will be used to summarize toxicities observed after TCR transgenic cell infusion in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity and nadir or maximum values for the laboratory measures, time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course.

  Up to 15 years

• Maximum tolerated dose based on dose-limiting toxicity using the Common Toxicity Criteria

  First 60 days after ACT

Secondary Outcomes (2)

• Feasibility of generating NY-ESO-1 TCR cells and/or NY-ESO 1(157-165) peptide pulsed DC vaccine, determined by the incidence of preparation not meeting the lot release criteria

  1 month

• Transgenic cell persistence

  Up to 15 years

Other Outcomes (2)

• Antitumor activity as determined by RECIST

  Up to 15 years

• NY-ESO-1 TCR transgenic cell tumor trafficking (imaging) using 18F-FDG PET

  Up to 40 days

Study Arms (1)

Treatment (NY-ESO-1 TCR transduced PBMC, vaccine, nivolumab)

EXPERIMENTAL

CONDITIONING REGIMEN: Patients receive cyclophosphamide IV over 1 hour on days -5 to -4 and fludarabine phosphate IV over 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 DC: Patients receive NY-ESO-1(157-165) peptide pulsed DC ID on days 1, 14, and 28. LOW DOSE ALDESLEUKIN ADMINISTRATION: Patients receive aldesleukin SC BID for 7 days beginning on day 1 for a maximum of 14 doses.

Biological: Aldesleukin; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Biological: NY-ESO-1 Reactive TCR Retroviral Vector Transduced Autologous PBL; Biological: NY-ESO-1(157-165) Peptide-pulsed Autologous Dendritic Cell Vaccine; Procedure: Positron Emission Tomography

Interventions

Aldesleukin BIOLOGICAL

Given SC

Also known as: 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2, Recombinant Human Interleukin-2

Treatment (NY-ESO-1 TCR transduced PBMC, vaccine, nivolumab)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (NY-ESO-1 TCR transduced PBMC, vaccine, nivolumab)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, Oforta, SH T 586

Treatment (NY-ESO-1 TCR transduced PBMC, vaccine, nivolumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (NY-ESO-1 TCR transduced PBMC, vaccine, nivolumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Treatment (NY-ESO-1 TCR transduced PBMC, vaccine, nivolumab)

NY-ESO-1 Reactive TCR Retroviral Vector Transduced Autologous PBL BIOLOGICAL

Given IV

Also known as: Anti-NY-ESO-1 TCR Retroviral Vector Transduced Autologous PBL

Treatment (NY-ESO-1 TCR transduced PBMC, vaccine, nivolumab)

NY-ESO-1(157-165) Peptide-pulsed Autologous Dendritic Cell Vaccine BIOLOGICAL

Given ID

Also known as: Autologous NY-ESO-1 (157-165) Peptide-pulsed DC Vaccine

Treatment (NY-ESO-1 TCR transduced PBMC, vaccine, nivolumab)

Positron Emission Tomography PROCEDURE

Correlative studies

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET SCAN, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging

Treatment (NY-ESO-1 TCR transduced PBMC, vaccine, nivolumab)

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Stage IV or locally advanced histologically confirmed solid tumors for which no alternative therapies with proven survival advantage are available
• At least 1 lesion amenable for outpatient biopsies; this should be a cutaneous or palpable metastatic site or a deeper site accessible by image-guided biopsy that is deemed safe to access by the treating physicians and interventional radiologists; patients without accessible lesions for biopsy but with prior tissue available from metastatic disease would be eligible at the investigator's discretion
• NY-ESO-1 positive malignancy by immunohistochemistry (IHC) utilizing commonly available NY-ESO-1 antibodies
• Human leukocyte antigen (HLA)-A\*0201 (HLA-A2.1) positivity by molecular subtyping
• Age greater than or equal to 16 years old
• A minimum of one measurable lesion defined as:
• Meeting the criteria for measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST)
• Skin lesion(s) selected as non-completely biopsied target lesion(s) that can be accurately measured and recorded by color photography with a ruler to document the size of the target lesion(s)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• Absolute neutrophil count \>= 1.5 x 10\^9 cells/L
• Platelets \>= 100 x 10\^9/L
• Hemoglobin \>= 9 g/dL
• Aspartate and alanine aminotransferases (AST, ALT) =\< 2.5 x upper limit of normal (ULN) (=\< 5 x ULN, if documented liver metastases are present)
• Total bilirubin =\< 2 x ULN (except patients with documented Gilbert's syndrome)
• Creatinine \< 2 mg/dl (or a glomerular filtration rate \> 60)

You may not qualify if:

• Previously known hypersensitivity to any of the agents used in this study
• Received systemic treatment for cancer, including immunotherapy, within one month prior to initiation of dosing within this protocol
• History of inflammatory bowel disease, celiac disease, or other chronic gastrointestinal conditions associated with diarrhea or bleeding, or current acute colitis of any origin
• Potential requirement for systemic corticosteroids or concurrent immunosuppressive drugs based on prior history or received systemic steroids within the last 2 weeks prior to enrollment (inhaled or topical steroids at standard doses are allowed)
• Human immunodeficiency virus (HIV) seropositivity or other congenital or acquired immune deficiency state; if there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and/or infectious disease specialist
• Hepatitis B or C seropositivity with evidence of ongoing liver damage; if there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and/or infectious disease specialist
• Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol
• Pregnancy or breast-feeding; female patients must be surgically sterile or be postmenopausal for two years, or must agree to use effective contraception during the period of treatment and 6 months after; all female patients with reproductive potential must have a negative pregnancy test (serum/urine) within 24 hours from starting the conditioning chemotherapy; the definition of effective contraception will be based on the judgment of the study investigators; patients who are breastfeeding are not allowed on study
• Since IL-2 is administered following cell infusion:
• Patients will be excluded if they have a history of clinically significant electrocardiogram (ECG) abnormalities, symptoms of cardiac ischemia or arrhythmias and have a left ventricular ejection fraction (LVEF) \< 45% on a cardiac stress test (stress thallium, stress multi gated acquisition scan \[MUGA\], dobutamine echocardiogram, or other stress test)
• Similarly, patients who are \>= 50 years old with a baseline LVEF \< 45% will be excluded
• Patients with ECG results of any conduction delays (PR interval \> 200 ms, corrected QT interval \[QTC\] \> 480 ms), sinus bradycardia (resting heart rate \< 50 beats per minute), sinus tachycardia (heart rate \> 120 beats per minute) will be evaluated by a cardiologist prior to starting the trial; patients with any arrhythmias, including atrial fibrillation/atrial flutter, excessive ectopy (defined as \> 20 premature ventricular contractions \[PVCs\] per minute), ventricular tachycardia, third (3rd) degree heart block will be excluded from the study unless cleared by a cardiologist
• Patients with pulmonary function test abnormalities as evidenced by a forced expiration volume in one second (FEV1)/forced vital capacity (FVC) \< 70% of predicted for normality will be excluded
• Evidence of diverticulitis at baseline, including evidence limited to computed tomography (CT) scan only
• Received 3 or more prior myelotoxic treatment regimens

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• Stand Up To Cancer: collaborator
• Bristol-Myers Squibb: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

Related Publications (1)

• Frankiw L, Singh A, Peters C, Comin-Anduix B, Berent-Maoz B, Macabali M, Shammaie K, Quiros C, Kaplan-Lefko P, Baselga Carretero I, Ribas A, Nowicki TS. Immunotherapy resistance driven by loss of NY-ESO-1 expression in response to transgenic adoptive cellular therapy with PD-1 blockade. J Immunother Cancer. 2023 May;11(5):e006930. doi: 10.1136/jitc-2023-006930.

  PMID: 37156551 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

aldesleukin; Cyclophosphamide; fludarabine phosphate; Nivolumab; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Antoni Ribas

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

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: May 13, 2016
• First Posted: May 17, 2016
• Study Start: January 3, 2017
• Primary Completion: April 8, 2019
• Study Completion: April 8, 2019
• Last Updated: July 30, 2025

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)