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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

NCT04526509

Description:

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

Related Conditions:
  • Non-Small Cell Lung Carcinoma
  • Synovial Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 209012
  • NCT ID: NCT04526509

Conditions

  • Neoplasms

Interventions

DrugSynonymsArms
GSK3901961Substudy 1: GSK3901961 in previously treated advanced SS
GSK3845097Substudy 2: GSK3845097 in previously treated advanced SS
FludarabineSubstudy 1: GSK3901961 in previously treated advanced SS
CyclophosphamideSubstudy 1: GSK3901961 in previously treated advanced SS

Purpose

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

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).
    

Trial Arms

NameTypeDescriptionInterventions
Substudy 1: GSK3901961 in previously treated advanced SSExperimentalEligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK3901961, as a single intravenous (IV) infusion after completing lymphodepleting chemotherapy.
  • GSK3901961
  • Fludarabine
  • Cyclophosphamide
Substudy 1: GSK3901961 in previously treated metastatic NSCLCExperimentalEligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK3901961, as a single IV infusion after completing lymphodepleting chemotherapy.
  • GSK3901961
  • Fludarabine
  • Cyclophosphamide
Substudy 2: GSK3845097 in previously treated advanced SSExperimentalEligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK3845097, as a single IV infusion after completing lymphodepleting chemotherapy.
  • GSK3845097
  • Fludarabine
  • Cyclophosphamide

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Substudy 1 and 2: Frequency of dose limiting toxicities (DLTs) according to severity.
Time Frame:Until disease progression (up to 4 years)
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Substudy 1 and 2: Overall response rate (ORR)
Time Frame:Until disease progression (up to 4 years)
Safety Issue:
Description: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.
Measure:Substudy 1 and 2: Duration of response (DOR)
Time Frame:Until disease progression (up to 4 years)
Safety Issue:
Description: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.
Measure:Substudy 2: Progression free survival (PFS)
Time Frame:Until disease progression (up to 4 years)
Safety Issue:
Description: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.
Measure:Substudy 2: Disease control rate (DCR)
Time Frame:Until disease progression (up to 4 years)
Safety Issue:
Description: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.
Measure:Substudy 2: Time to response
Time Frame:Until disease progression (up to 4 years)
Safety Issue:
Description: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).
Measure:Substudy 1 and 2: Maximum expansion/persistence (Cmax)
Time Frame:Until disease progression (up to 4 years)
Safety Issue:
Description:Whole blood samples will be collected at indicated time points for evaluation of Cmax.
Measure:Substudy 1 and 2: Time to Cmax (Tmax)
Time Frame:Until disease progression (up to 4 years)
Safety Issue:
Description:Whole blood samples will be collected at indicated time points for evaluation of Tmax.
Measure: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)
Safety Issue:
Description:Whole blood samples will be collected at indicated time points for evaluation of AUC (0 to t).
Measure:Substudy 1 and 2: Phenotype of transduced T cells
Time Frame:Until disease progression (up to 4 years)
Safety Issue:
Description:Tumor samples will be collected to assess phenotype of transduced T cells.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:GlaxoSmithKline

Trial Keywords

  • Adoptive T-cell therapy
  • Advanced synovial sarcoma
  • Advanced non-small cell lung cancer
  • Advanced tumors
  • GSK3845097
  • GSK3901961
  • T cell receptors
  • Leukapheresis

Last Updated

April 5, 2021