NCT04526509

Brief Summary

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

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
12

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Dec 2020

Typical duration for phase_1

Geographic Reach
6 countries

17 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 21, 2020

Completed
4 days until next milestone

First Posted

Study publicly available on registry

August 25, 2020

Completed
4 months until next milestone

Study Start

First participant enrolled

December 21, 2020

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 8, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 8, 2023

Completed
11 months until next milestone

Results Posted

Study results publicly available

May 10, 2024

Completed
Last Updated

November 26, 2024

Status Verified

November 1, 2024

Enrollment Period

2.5 years

First QC Date

August 21, 2020

Results QC Date

December 1, 2023

Last Update Submit

November 8, 2024

Conditions

Keywords

Adoptive T-cell therapyAdvanced synovial sarcomaAdvanced non-small cell lung cancerAdvanced tumorsGSK3845097GSK3901961GSK4427296T cell receptorsLeukapheresisAdvanced myxoid/round cell liposarcoma

Outcome Measures

Primary Outcomes (1)

  • Number of Participants Enrolled Across Sub Studies

    Number of Participants Randomized across sub studies are presented.

    Day -7

Study Arms (4)

Substudy 1: Cohort 1 - GSK3901961 in previously treated metastatic NSCLC

EXPERIMENTAL

Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK3901961, as intravenous (IV) infusion after completing lymphodepleting chemotherapy.

Drug: GSK3901961Drug: CyclophosphamideDrug: Fludarabine

Substudy 1: Cohort 2 - GSK3901961 in previously treated advanced SS or MRCLS

EXPERIMENTAL

Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK3901961, as IV infusion after completing lymphodepleting chemotherapy.

Drug: GSK3901961Drug: CyclophosphamideDrug: Fludarabine

Substudy 2: GSK3845097 in previously treated advanced SS or MRCLS

EXPERIMENTAL

Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK3845097, as IV infusion after completing lymphodepleting chemotherapy.

Drug: GSK3845097Drug: CyclophosphamideDrug: Fludarabine

Substudy 3: GSK4427296 in previously treated advanced SS or MRCLS

EXPERIMENTAL

Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK4427296, as IV infusion after completing lymphodepleting chemotherapy.

Drug: GSK4427296Drug: CyclophosphamideDrug: Fludarabine

Interventions

GSK3901961 as an IV infusion.

Substudy 1: Cohort 1 - GSK3901961 in previously treated metastatic NSCLCSubstudy 1: Cohort 2 - GSK3901961 in previously treated advanced SS or MRCLS

GSK3845097 as an IV infusion.

Substudy 2: GSK3845097 in previously treated advanced SS or MRCLS

GSK4427296 as an IV infusion.

Substudy 3: GSK4427296 in previously treated advanced SS or MRCLS

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

Substudy 1: Cohort 1 - GSK3901961 in previously treated metastatic NSCLCSubstudy 1: Cohort 2 - GSK3901961 in previously treated advanced SS or MRCLSSubstudy 2: GSK3845097 in previously treated advanced SS or MRCLSSubstudy 3: GSK4427296 in previously treated advanced SS or MRCLS

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

Substudy 1: Cohort 1 - GSK3901961 in previously treated metastatic NSCLCSubstudy 1: Cohort 2 - GSK3901961 in previously treated advanced SS or MRCLSSubstudy 2: GSK3845097 in previously treated advanced SS or MRCLSSubstudy 3: GSK4427296 in previously treated advanced SS or MRCLS

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (17)

GSK Investigational Site

Jacksonville, Florida, 32224, United States

Location

GSK Investigational Site

Atlanta, Georgia, 30322, United States

Location

GSK Investigational Site

Westwood, Kansas, 66205, United States

Location

GSK Investigational Site

Lexington, Kentucky, 40536, United States

Location

GSK Investigational Site

Baltimore, Maryland, 21287, United States

Location

GSK Investigational Site

St Louis, Missouri, 63110, United States

Location

GSK Investigational Site

New York, New York, 10032, United States

Location

GSK Investigational Site

New York, New York, 10065, United States

Location

GSK Investigational Site

Houston, Texas, 77030, United States

Location

GSK Investigational Site

Melbourne, Victoria, 3000, Australia

Location

GSK Investigational Site

Toronto, Ontario, M5G 2M9, Canada

Location

GSK Investigational Site

Montreal, Quebec, H1T 2M4, Canada

Location

GSK Investigational Site

Munich, Bavaria, 81377, Germany

Location

GSK Investigational Site

Cologne, North Rhine-Westphalia, 50937, Germany

Location

GSK Investigational Site

Dresden, Saxony, 01307, Germany

Location

GSK Investigational Site

Amsterdam, 1066 CX, Netherlands

Location

GSK Investigational Site

Stockholm, SE-171 64, Sweden

Location

MeSH Terms

Conditions

NeoplasmsLiposarcoma, Myxoid

Interventions

Cyclophosphamidefludarabine

Condition Hierarchy (Ancestors)

LiposarcomaNeoplasms, Adipose TissueNeoplasms, Connective and Soft TissueNeoplasms by Histologic TypeSarcoma

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus Compounds

Results Point of Contact

Title
GSK Response Center
Organization
GlaxoSmithKline

Study Officials

  • Adaptimmune Patient Enquiries

    Adaptimmune

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Masking Details
This will be an open-label study. Hence, there will be no masking
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 21, 2020

First Posted

August 25, 2020

Study Start

December 21, 2020

Primary Completion

June 8, 2023

Study Completion

June 8, 2023

Last Updated

November 26, 2024

Results First Posted

May 10, 2024

Record last verified: 2024-11

Data Sharing

IPD Sharing
Will share

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

Shared Documents
STUDY PROTOCOL, SAP, ICF, 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.
More information

Locations