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Trial record 1 of 1 for:    NCT04526509
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Master Protocol to Assess 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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04526509
Recruitment Status : Active, not recruiting
First Posted : August 25, 2020
Last Update Posted : December 29, 2022
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Description
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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: GSK4427296 Drug: Cyclophosphamide Drug: Fludarabine 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, GSK3845097 and GSK4427296 are next generation engineered T-cell receptor (TCR) T-cells, co-expressing the cluster of differentiation 8 (CD8) alpha cell surface receptor, targeting NY-ESO-1, co-expressing the dominant-negative TGF-beta receptor type II (dnTGF-beta RII) cell surface receptor, targeting NY-ESO-1, and engineered using the Epigenetically Reprogrammed (Epi-R) manufacturing process, respectively to potentially improve function. This is a master protocol evaluating first time in human T-cell therapies. It currently consists of three independent substudies, investigating GSK3901961, GSK3845097 and GSK4427296 in human leukocyte antigen (HLA)-A*02 positive participants with NYESO1+ previously treated advanced (metastatic or unresectable) synovial sarcoma (SS)/myxoid/round cell liposarcoma (MRCLS) and/or previously treated metastatic non-small cell lung cancer (NSCLC).
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 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 : December 4, 2025
Estimated Study Completion Date : December 4, 2025

Resource links provided by the National Library of Medicine


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

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

Drug: Fludarabine
Fludarabine will be used as lymphodepleting chemotherapy and will be administered via IV route.
Experimental: Substudy 1: Cohort 2 - GSK3901961 in previously treated advanced SS or MRCLS
Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK3901961, as IV infusion after completing lymphodepleting chemotherapy.
 Drug: GSK3901961
GSK3901961 as an IV infusion.

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

Drug: Fludarabine
Fludarabine will be used as lymphodepleting chemotherapy and will be administered via IV route.
Experimental: Substudy 2: GSK3845097 in previously treated advanced SS or MRCLS
Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK3845097, as IV infusion after completing lymphodepleting chemotherapy.
 Drug: GSK3845097
GSK3845097 as an IV infusion.

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

Drug: Fludarabine
Fludarabine will be used as lymphodepleting chemotherapy and will be administered via IV route.
Experimental: Substudy 3: GSK4427296 in previously treated advanced SS or MRCLS
Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK4427296, as IV infusion after completing lymphodepleting chemotherapy.
 Drug: GSK4427296
GSK4427296 as an IV infusion.

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

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


Outcome Measures
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Primary Outcome Measures :
  1. Substudy 1, 2 and 3: Frequency of dose limiting toxicities (DLTs) [ 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.

  2. Substudy 1, 2 and 3: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, 2 and 3: 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 relevant cohort and 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, 2 and 3: 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 1, 2 and 3: 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.

  4. Substudy 1, 2 and 3 : 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.

  5. Substudy 1, 2 and 3: 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).


Eligibility Criteria
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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 and weighs ≥40 kg on the day of signing informed consent
  • Participant must be positive for HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 alleles
  • Participant's tumor must have tested positive for NY-ESO-1 and/or LAGE-1a expression by a GSK designated 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 SS/ MRCLS:

  • Participant has advanced (metastatic or unresectable) SS or MRCLS confirmed by local histopathology with evidence of disease-specific translocation
  • Participant has completed at least one standard of care (SOC) treatment including anthracycline containing regimen unless intolerant to or ineligible to receive the therapy. Participants who are not candidates to receive anthracycline should have received ifosfamide unless also intolerant to or ineligible to receive ifosfamide. Participants who received neoadjuvant/adjuvant anthracycline or ifosfamide based therapy and progressed will be eligible

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

  • Participant has Stage IV NSCLC as confirmed by histology or cytology
  • Prior therapies for participants lacking actionable genetic aberrations (i.e., wild type), per National Comprehensive Cancer Network (NCCN) guidelines: participant has been previously treated with or is intolerant to programmed death receptor-1 (PD)-1/Programmed death ligand 1 (PD-L1) checkpoint blockade therapy and has been previously treated with or is intolerant to a platinum-based chemotherapy. Adjuvant therapy will count as a regimen if completed within 6 months before relapse. Or for participants that harbors an actionable genetic aberration (e.g. BRAF, anaplastic lymphoma kinase [ALK]/ c-ros oncogene 1 [ROS1] etc.), per NCCN guidelines: participants has been previously treated with or is intolerant to SOC therapy, including targeted therapy, as recommended by NCCN or equivalent country-level guidelines (European Society for Medical Oncology [ESMO], National Institute for Health & Care Excellence [NICE]) . Or Investigator has decided that additional lines of SOC therapy after the first line are not in the participant's best interest.

Exclusion criteria:

  • Central nervous system (CNS) metastases, with certain exceptions for CNS metastases in 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, NY-ESO-1 vaccine or NY-ESO-1 targeting antibody
  • Prior gene therapy using an integrating vector
  • Previous allogeneic hematopoietic stem cell transplant within the last 5 years or solid organ transplant
  • Washout periods for prior radiotherapy and systemic chemotherapy must be followed
  • Major surgery within 4 weeks prior to lymphodepletion
  • Pregnant or breastfeeding females
Contacts and Locations
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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


Locations
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United States, Connecticut
GSK Investigational Site
New Haven, Connecticut, United States, 06504
United States, Florida
GSK Investigational Site
Jacksonville, Florida, United States, 32224
GSK Investigational Site
Tampa, Florida, United States, 33612
United States, Georgia
GSK Investigational Site
Atlanta, Georgia, United States, 30322
United States, Kansas
GSK Investigational Site
Westwood, Kansas, United States, 66205
United States, Kentucky
GSK Investigational Site
Lexington, Kentucky, United States, 40536
United States, Maryland
GSK Investigational Site
Baltimore, Maryland, United States, 21287
United States, Missouri
GSK Investigational Site
Saint Louis, Missouri, United States, 63110
United States, New York
GSK Investigational Site
New York, New York, United States, 10032
GSK Investigational Site
New York, New York, United States, 10065
United States, Pennsylvania
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19111
United States, Texas
GSK Investigational Site
Houston, Texas, United States, 77030
Australia, Victoria
GSK Investigational Site
Melbourne, Victoria, Australia, 3000
Canada, Ontario
GSK Investigational Site
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
GSK Investigational Site
Montreal, Quebec, Canada, H1T 2M4
Germany
GSK Investigational Site
Muenchen, Bayern, Germany, 81377
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30625
GSK Investigational Site
Koeln, Nordrhein-Westfalen, Germany, 50937
GSK Investigational Site
Dresden, Sachsen, Germany, 01307
Netherlands
GSK Investigational Site
Amsterdam, Netherlands, 1066 CX
Sweden
GSK Investigational Site
Stockholm, Sweden, SE-171 64
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
More Information
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT04526509    
Other Study ID Numbers: 209012
2019-004446-14 ( EudraCT Number )
First Posted: August 25, 2020    Key Record Dates
Last Update Posted: December 29, 2022
Last Verified: December 2022
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
GSK4427296
T cell receptors
Leukapheresis
Advanced myxoid/round cell liposarcoma
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