A Pilot Study of Genetically Engineered NY-ESO-1 Specific NY-ESO-1ᶜ²⁵⁹T in HLA-A2+ Patients With Synovial Sarcoma

NCT01343043 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: 208466ADP 045112015-005594-21
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 8

Brief Summary

The purpose of this early (pilot) clinical trial is to test the effects (both good and bad) of chemotherapy and adoptive immunotherapy with T cells engineered to recognize NY-ESO-1 peptide in patients with unresectable, metastatic or recurrent synovial sarcoma.

Conditions

Neoplasms

Keywords

T Cell Receptor; Sarcoma; Cell Therapy; T Cell Therapy; Previously treated; NY-ESO-1; Metastatic; Immuno-oncology

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR was calculated as the percentage of participants with a confirmed complete response (CR) or partial response (PR) relative to the total number of participants in the analysis population per response evaluation criteria in solid tumors (RECIST) version (v)1.1 as determined by the local investigators.

  Up to 4.5 years

Secondary Outcomes (13)

• Duration of Overall Response

  Up to 4.5 years

• Progression Free Survival

  Up to 4.5 years

• Best Overall Response

  Up to 4.5 years

• Overall Survival

  Up to 4.5 years

• Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)

  Up to 5 years

Other Outcomes (3)

• Number of Participants With Dose-limiting Toxicities (DLTs)

  Up to Day 21 (from first dose)

• Number of Participants With Clinically Significant Abnormal Electrocardiogram, Echocardiogram and Multigated Acquisition Scan Findings

  Up to 4.5 years

• Percentage of Participants With Confirmed CR

  Up to 4.5 years

Study Arms (4)

Cohort 1 treated with NY-ESO-1 T Cells

EXPERIMENTAL

High NY-ESO-1 expression and the use of cyclophosphamide plus fludarabine as the lymphodepleting chemotherapy.

Drug: NY-ESO-1(c259)T Cells; Drug: Fludarabine; Drug: Cyclophosphamide

Cohort 2 treated with NY-ESO-1 T Cells

EXPERIMENTAL

Low NY-ESO-1 expression and the use of cyclophosphamide plus fludarabine as the lymphodepleting chemotherapy.

Drug: NY-ESO-1(c259)T Cells; Drug: Fludarabine; Drug: Cyclophosphamide

Cohort 3 treated with NY-ESO-1 T Cells

EXPERIMENTAL

High NYESO-1 expression and the use of cyclophosphamide only for lymphodepletion rather than fludarabine as the lymphodepleting chemotherapy.

Drug: NY-ESO-1(c259)T Cells; Drug: Cyclophosphamide

Cohort 4 treated with NY-ESO-1 T Cells

EXPERIMENTAL

High NY-ESO-1 expression and the use of reduced dose cyclophosphamide plus fludarabine regimen as the lymphodepleting chemotherapy.

Drug: NY-ESO-1(c259)T Cells; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

NY-ESO-1(c259)T Cells DRUG

Lymphodepleting chemotherapy followed by infusion with NY-ESO-1(c259) transduced autologous T cells. Subjects will receive one infusion of NY-ESO-1 genetically engineered T cells on Day 0.

Cohort 1 treated with NY-ESO-1 T Cells; Cohort 2 treated with NY-ESO-1 T Cells; Cohort 3 treated with NY-ESO-1 T Cells; Cohort 4 treated with NY-ESO-1 T Cells

Fludarabine DRUG

Fludarabine will be used as lymphodepleting chemotherapy.

Cohort 1 treated with NY-ESO-1 T Cells; Cohort 2 treated with NY-ESO-1 T Cells; Cohort 4 treated with NY-ESO-1 T Cells

Cyclophosphamide DRUG

Cyclophosphamide will be used as lymphodepleting chemotherapy.

Cohort 1 treated with NY-ESO-1 T Cells; Cohort 2 treated with NY-ESO-1 T Cells; Cohort 3 treated with NY-ESO-1 T Cells; Cohort 4 treated with NY-ESO-1 T Cells

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Synovial sarcoma that has been treated with standard chemotherapy containing ifosfamide and/or doxorubicin and remains: unresectable or metastatic or progressive/persistent or recurrent disease
• Measurable disease
• Patients must have proven positive tumor sample for NY-ESO-1 as follows:
• Cohort 1 -Positive expression is defined as 2+ and/or 3+ by immunohistochemistry in ≥ 50% of cells.
• Cohort 2 -Positive expression is defined as ≥1+ by immunohistochemistry in ≥1% cells, but not to exceed 2+ and/or 3+ in ≥ 50% of cells.
• Cohort 3 -Positive expression is defined as 2+ and/or 3+ by immunohistochemistry in ≥ 50% of cells.
• Cohort 4 -Positive expression is defined as 2+ and/or 3+ by immunohistochemistry in ≥ 50% of cells.
• HLA-A\*02:01, HLA-A\*02:05, and/or HLA-A\*02:06 by high resolution testing at a local or central laboratory
• Weigh more than 18 kg
• All previous cytotoxic chemotherapy, monoclonal antibody therapy, or immune therapy must be washed out 3 weeks before apheresis and must be completed at least 3 weeks prior to pre-infusion lymphodepletive chemotherapy.
• Systemic corticosteroid or other immunosuppressive therapy should be washed out 2 weeks before apheresis and must be completed at least 2 weeks prior to pre-infusion lymphodepletive chemotherapy.
• Biologic or other approved molecular targeted small molecule inhibitors should be washed out 1 week or 5 half-lives (whichever is longer) before apheresis and must be completed at least 1 week or 5 half-lives (whichever is longer) prior to pre-infusion lymphodepletive chemotherapy.
• Any grade 3 or 4 hematologic toxicity of any previous therapy must have resolved to grade 2 or less prior to apheresis and any grade 3 or 4 toxicity must have resolved to grade 2 or less prior to pre-infusion lymphodepletive chemotherapy.
• ECOG 0-1, or for children ≤10 years of age, Lansky \> 60
• Life expectancy \> 3 months

You may not qualify if:

• Active HIV, HBV, HCV or HTLV 1/2 infection (due to increased risk of complications during lymphodepleting regimen and confounding effects on the immune system). Active hepatitis B or C infection is defined by seropositive for hepatitis B surface antigen (HbSAg) or hepatitis C antibody.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (8)

GSK Investigational Site

Duarte, California, 91010, United States

Location

GSK Investigational Site

Miami, Florida, 33136, United States

Location

GSK Investigational Site

Tampa, Florida, 33612, United States

Location

GSK Investigational Site

Bethesda, Maryland, 20892, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02114, United States

Location

GSK Investigational Site

St Louis, Missouri, 63110, United States

Location

GSK Investigational Site

New York, New York, 10065, United States

Location

GSK Investigational Site

Houston, Texas, 77030, United States

Location

Related Publications (3)

• Gyurdieva A, Zajic S, Chang YF, Houseman EA, Zhong S, Kim J, Nathenson M, Faitg T, Woessner M, Turner DC, Hasan AN, Glod J, Kaplan RN, D'Angelo SP, Araujo DM, Chow WA, Druta M, Demetri GD, Van Tine BA, Grupp SA, Fine GD, Eleftheriadou I. Biomarker correlates with response to NY-ESO-1 TCR T cells in patients with synovial sarcoma. Nat Commun. 2022 Sep 8;13(1):5296. doi: 10.1038/s41467-022-32491-x.

  PMID: 36075914 DERIVED

• Ramachandran I, Lowther DE, Dryer-Minnerly R, Wang R, Fayngerts S, Nunez D, Betts G, Bath N, Tipping AJ, Melchiori L, Navenot JM, Glod J, Mackall CL, D'Angelo SP, Araujo DM, Chow WA, Demetri GD, Druta M, Van Tine BA, Grupp SA, Abdul Razak AR, Wilky B, Iyengar M, Trivedi T, Winkle EV, Chagin K, Amado R, Binder GK, Basu S. Systemic and local immunity following adoptive transfer of NY-ESO-1 SPEAR T cells in synovial sarcoma. J Immunother Cancer. 2019 Oct 24;7(1):276. doi: 10.1186/s40425-019-0762-2.

  PMID: 31651363 DERIVED

• D'Angelo SP, Melchiori L, Merchant MS, Bernstein D, Glod J, Kaplan R, Grupp S, Tap WD, Chagin K, Binder GK, Basu S, Lowther DE, Wang R, Bath N, Tipping A, Betts G, Ramachandran I, Navenot JM, Zhang H, Wells DK, Van Winkle E, Kari G, Trivedi T, Holdich T, Pandite L, Amado R, Mackall CL. Antitumor Activity Associated with Prolonged Persistence of Adoptively Transferred NY-ESO-1 c259T Cells in Synovial Sarcoma. Cancer Discov. 2018 Aug;8(8):944-957. doi: 10.1158/2159-8290.CD-17-1417. Epub 2018 Jun 11.

  PMID: 29891538 DERIVED

MeSH Terms

Conditions

Neoplasms; Sarcoma; Neoplasm Metastasis

Interventions

fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplastic Processes; 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

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2011
• First Posted: April 27, 2011
• Study Start: September 27, 2012
• Primary Completion: June 18, 2019
• Study Completion: June 18, 2019
• Last Updated: June 30, 2021
• Results First Posted: July 9, 2020

Record last verified: 2021-06

Locations

US (8)