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Master Protocol to Assess the Safety and Dose of First Time in Human Next Generation Engineered T Cells in NY-ESO-1 and/or LAGE-1a Positive Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT04526509
Recruitment Status : Recruiting
First Posted : August 25, 2020
Last Update Posted : May 7, 2021
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
This trial will evaluate the safety and efficacy of first time in human engineered T-cell therapies, in participants with advanced tumors.

Condition or disease Intervention/treatment Phase
Neoplasms Drug: GSK3901961 Drug: GSK3845097 Drug: Fludarabine Drug: Cyclophosphamide Phase 1

Detailed Description:
New York esophageal antigen-1 (NY-ESO-1) and LAGE-1a antigens are tumor-associated proteins that have been found in several tumor types. Clinical trials using adoptively transferred T-cells directed against NY-ESO-1 have shown objective responses. GSK3901961 and GSK3845097 are next generation engineered TCR T-cells, co-expressing the CD8α cell surface receptor, targeting NY-ESO-1, and co-expressing the dnTGF-βRII cell surface receptor, targeting NY-ESO-1, respectively to potentially improve function. This is a master protocol evaluating first time in human T-cell therapies. It will initially consist of two independent substudies, investigating GSK3901961 and GSK3845097 in HLA*A02+ participants with NYESO1+ previously treated advanced (metastatic or unresectable) synovial sarcoma (SS) and/or previously treated metastatic non-small cell lung cancer (NSCLC).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 38 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description: This will be an open-label study. Hence, there will be no masking
Primary Purpose: Treatment
Official Title: Master Protocol to Assess the Safety and Recommended Phase 2 Dose of Next Generations of Autologous Enhanced NY-ESO-1/ LAGE-1a TCR Engineered T-cells, Alone or in Combination With Other Agents, in Participants With Advanced Tumors
Actual Study Start Date : December 21, 2020
Estimated Primary Completion Date : February 12, 2024
Estimated Study Completion Date : February 12, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Substudy 1: GSK3901961 in previously treated advanced SS
Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK3901961, as a single intravenous (IV) infusion after completing lymphodepleting chemotherapy.
Drug: GSK3901961
GSK3901961 as an IV infusion.

Drug: Fludarabine
Fludarabine will be used as lymphodepleting chemotherapy and will be administered via IV route.

Drug: Cyclophosphamide
Cyclophosphamide will be used as lymphodepleting chemotherapy and will be administered via IV route.

Experimental: Substudy 1: GSK3901961 in previously treated metastatic NSCLC
Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK3901961, as a single IV infusion after completing lymphodepleting chemotherapy.
Drug: GSK3901961
GSK3901961 as an IV infusion.

Drug: Fludarabine
Fludarabine will be used as lymphodepleting chemotherapy and will be administered via IV route.

Drug: Cyclophosphamide
Cyclophosphamide will be used as lymphodepleting chemotherapy and will be administered via IV route.

Experimental: Substudy 2: GSK3845097 in previously treated advanced SS
Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK3845097, as a single IV infusion after completing lymphodepleting chemotherapy.
Drug: GSK3845097
GSK3845097 as an IV infusion.

Drug: Fludarabine
Fludarabine will be used as lymphodepleting chemotherapy and will be administered via IV route.

Drug: Cyclophosphamide
Cyclophosphamide will be used as lymphodepleting chemotherapy and will be administered via IV route.




Primary Outcome Measures :
  1. Substudy 1 and 2: Frequency of dose limiting toxicities (DLTs) according to severity. [ Time Frame: Until disease progression (up to 4 years) ]
    Toxicities will be considered DLTs if they are considered at least possibly related to transduced T-cells; and they occur within the DLT-assessment period. Severity will be summarized using National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 5.0

  2. Substudy 1 and 2:Frequency of adverse events (AEs), serious adverse events (SAEs) and AEs of special interest (AESI) according to severity [ Time Frame: Until disease progression (up to 4 years) ]
    AEs, SAEs and AESIs will be collected. Severity of AEs and SAEs will be summarized using NCI-CTCAE, version 5.0.


Secondary Outcome Measures :
  1. Substudy 1 and 2: Overall response rate (ORR) [ Time Frame: Until disease progression (up to 4 years) ]
    Overall response rate is defined as the percentage of participants with a confirmed complete response (CR) or a confirmed partial response (PR) relative to the total number of participants within the analysis population at any time per Response evaluation criteria in solid tumors (RECIST) version 1.1 as determined by the local investigators.

  2. Substudy 1 and 2: Duration of response (DOR) [ Time Frame: Until disease progression (up to 4 years) ]
    Duration of response is defined as, in the subset of participants who show a confirmed CR or PR as assessed by local investigators, the time from first documented evidence of CR or PR until the first documented sign of disease progression or death.

  3. Substudy 2: Progression free survival (PFS) [ Time Frame: Until disease progression (up to 4 years) ]
    Progression free survival is defined as the time from the date of T-cell infusion until first documented sign of disease progression, RECIST 1.1 or death.

  4. Substudy 2: Disease control rate (DCR) [ Time Frame: Until disease progression (up to 4 years) ]
    Disease control rate is defined as the percentage of participants with a confirmed CR, PR, or stable disease (SD) with minimal 12 weeks duration relative to the total number of participants within the analysis population at any time per RECIST version 1.1 as determined by the local investigators.

  5. Substudy 2: Time to response [ Time Frame: Until disease progression (up to 4 years) ]
    Time to response is defined as time from date of T-cell infusion to first documented evidence of confirmed CR and PR (RECIST version 1.1).

  6. Substudy 1 and 2: Maximum expansion/persistence (Cmax) [ Time Frame: Until disease progression (up to 4 years) ]
    Whole blood samples will be collected at indicated time points for evaluation of Cmax.

  7. Substudy 1 and 2: Time to Cmax (Tmax) [ Time Frame: Until disease progression (up to 4 years) ]
    Whole blood samples will be collected at indicated time points for evaluation of Tmax.

  8. Substudy 1 and 2: Area under the concentration/persistence time curve from zero to time t (AUC[0-t]) [ Time Frame: Until disease progression (up to 4 years) ]
    Whole blood samples will be collected at indicated time points for evaluation of AUC (0 to t).

  9. Substudy 1 and 2: Phenotype of transduced T cells [ Time Frame: Until disease progression (up to 4 years) ]
    Tumor samples will be collected to assess phenotype of transduced T cells.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Eligibility Criteria: Inclusion criteria:

  • Participant must be >=18 years of age on the day of signing informed consent.
  • Participant must be positive for Human leukocyte antigen (HLA)-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 alleles
  • Participant's tumor is positive for NY-ESO-1 expression by a designated central laboratory.
  • Performance status: Eastern Cooperative Oncology Group of 0-1.
  • Participant must have adequate organ function and blood cell counts 7 days prior to leukapheresis.
  • Participant must have measurable disease according to RECIST v1.1 Additional criteria for participants with synovial sarcoma
  • Participant has advanced (metastatic or unresectable) synovial sarcoma confirmed by histology.
  • Participant has received/completed treatment with anthracycline or anthracycline with ifosfamide for advanced (metastatic or inoperable) disease and progressed.

Additional criteria for participants with non-small cell lung cancer (NSCLC):

  • Participant has Stage IV NSCLC as confirmed by histology or cytology.
  • Participant has been previously treated with or is intolerant to programmed death receptor-1 (PD)-1/Programmed cell death ligand 1 (PD-L1) checkpoint blockade therapy and doublet taxane & platinum chemotherapy.

Exclusion criteria:

  • Central nervous system metastases, except in rare cases of NSCLC as specified in the protocol.
  • Any other prior malignancy that is not in complete remission.
  • Clinically significant systemic illness.
  • Prior or active demyelinating disease.
  • History of chronic or recurrent (within the last year prior to leukapheresis) severe autoimmune or immune mediated disease requiring steroids or other immunosuppressive treatments.
  • Previous treatment with genetically engineered NY-ESO-1-specific T cells.
  • Previous NY-ESO-1 vaccine or NY-ESO-1 targeting antibody.
  • Prior gene therapy using an integrating vector.
  • Previous allogeneic hematopoietic stem cell transplant.
  • Washout periods for prior radiotherapy and systemic chemotherapy must be followed.
  • Major surgery <=28 days of first dose of study intervention.
  • For participants with NSCLC that harbors an actionable genetic aberration, e.g. BRAF, anaplastic lymphoma kinase (ALK)/ c-ros oncogene 1 (ROS1) or others, has received and failed >=3 lines of systemic therapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04526509


Contacts
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Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com

Locations
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United States, Georgia
GSK Investigational Site Recruiting
Atlanta, Georgia, United States, 30322
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Taofeek Kunle Owonikoko         
United States, Kansas
GSK Investigational Site Recruiting
Westwood, Kansas, United States, 66205
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Benjamin Powers         
United States, Kentucky
GSK Investigational Site Recruiting
Lexington, Kentucky, United States, 40536
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Reema Anil Patel         
United States, Missouri
GSK Investigational Site Recruiting
Saint Louis, Missouri, United States, 63110
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Brian Van Tine         
United States, New York
GSK Investigational Site Recruiting
New York, New York, United States, 10065
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Adam Schoenfeld         
United States, Texas
GSK Investigational Site Recruiting
Houston, Texas, United States, 77030
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Dejka Araujo         
Canada, Quebec
GSK Investigational Site Recruiting
Montreal, Quebec, Canada, H1T 2M4
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Jonathan Noujaim         
Sweden
GSK Investigational Site Recruiting
Stockholm, Sweden, SE-171 64
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Jeffrey Yachnin         
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT04526509    
Other Study ID Numbers: 209012
First Posted: August 25, 2020    Key Record Dates
Last Update Posted: May 7, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
Adoptive T-cell therapy
Advanced synovial sarcoma
Advanced non-small cell lung cancer
Advanced tumors
GSK3845097
GSK3901961
T cell receptors
Leukapheresis
Additional relevant MeSH terms:
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Cyclophosphamide
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists