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

November 8, 2024 updated by: Adaptimmune

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

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This study is a master protocol. It has two sub studies registered as 209012 Sub Study 1 (NCT06048705) and 209012 Sub Study 2 (NCT05943990).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
12

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Victoria
      • Melbourne, Victoria, Australia, 3000
        • GSK Investigational Site
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • GSK Investigational Site
    • Quebec
      • Montreal, Quebec, Canada, H1T 2M4
        • GSK Investigational Site
  • Germany
    • Bayern
      • Muenchen, Bayern, Germany, 81377
        • GSK Investigational Site
    • Nordrhein-Westfalen
      • Koeln, Nordrhein-Westfalen, Germany, 50937
        • GSK Investigational Site
    • Sachsen
      • Dresden, Sachsen, Germany, 01307
        • GSK Investigational Site
  • Netherlands
      • Amsterdam, Netherlands, 1066 CX
        • GSK Investigational Site
  • Sweden
      • Stockholm, Sweden, SE-171 64
        • GSK Investigational Site
  • United States
    • Florida
      • Jacksonville, Florida, United States, 32224
        • GSK Investigational Site
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • GSK Investigational Site
    • Kansas
      • Westwood, Kansas, United States, 66205
        • GSK Investigational Site
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • GSK Investigational Site
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • GSK Investigational Site
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • GSK Investigational Site
    • New York
      • New York, New York, United States, 10032
        • GSK Investigational Site
      • New York, New York, United States, 10065
        • GSK Investigational Site
    • Texas
      • Houston, Texas, United States, 77030
        • GSK Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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: 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.
Drug: GSK3845097
GSK3845097 as an IV infusion.
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: 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.
Drug: GSK4427296
GSK4427296 as an IV infusion.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants Enrolled Across Sub Studies
Time Frame: Day -7
Number of Participants Randomized across sub studies are presented.
Day -7

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Until disease progression (up to 4 years)
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.
Until disease progression (up to 4 years)
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.
Until disease progression (up to 4 years)
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.
Until disease progression (up to 4 years)
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).
Until disease progression (up to 4 years)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Adaptimmune

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Adaptimmune Patient Enquiries, Adaptimmune

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 21, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 8, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 8, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 21, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 21, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 25, 2020

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 26, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 8, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 209012
  • 2019-004446-14 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

IPD for this study will be made available via the Clinical Study Data Request site.

IPD Sharing 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

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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