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Study of GSK3845097 in Previously Treated Participants With Advanced Synovial Sarcoma and Myxoid/Round Cell Liposarcoma

Primary Purpose

Neoplasms

Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
GSK3845097
Cyclophosphamide
Fludarabine
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neoplasms focused on measuring Adoptive T-cell therapy, Advanced synovial sarcoma, Advanced Myxoid/Round Cell Liposarcoma, Advanced tumors, GSK3845097, T cell receptor, Leukapheresis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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. 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 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

Sites / Locations

  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

GSK3845097

Arm Description

Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive high dose of GSK3845097 after completing lymphodepleting chemotherapy. The first study participant receiving GSK3845097 will receive the total assigned dose as 2 separate infusions 7 days apart, in aliquots of 30% (first infusion) and 70% (second infusion) of the total target dose , respectively. Based on the dose limiting toxicities reported in the first participant, then all subsequent participants treated with GSK3845097 will receive the full dose as a single, i.e., one-time, infusion.

Outcomes

Primary Outcome Measures

Number of Participants with Dose Limiting Toxicities (DLTs)
Number of Participants with Adverse Events (AEs), Serious AEs and Adverse Events of Special Interest (AESI) based on Severity

Secondary Outcome Measures

Overall Response Rate (ORR) assessed by investigator according to RECIST v1.1
Overall response rate was 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.
Duration of Response (DoR)
Duration of response was 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.
Maximum transgene expansion (Cmax)
Time to Cmax (Tmax)
Area under the concentration time curve from zero to time t AUC(0-t)

Full Information

First Posted
July 5, 2023
Last Updated
July 5, 2023
Sponsor
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT05943990
Brief Title
Study of GSK3845097 in Previously Treated Participants With Advanced Synovial Sarcoma and Myxoid/Round Cell Liposarcoma
Official Title
Assessment of Safety and Recommended Phase 2 Dose of Autologous T Cells Engineered With an Affinity-enhanced TCR Targeting NY ESO 1 and LAGE 1a, and Co-expressing the dnTGF-βRII (GSK3845097) in Participants With NY ESO 1 and/or LAGE 1a Positive Previously Treated Advanced (Metastatic or Unresectable) Synovial Sarcoma and Myxoid/Round Cell Liposarcoma
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Terminated
Why Stopped
The study was terminated due to a change in GSK's R&D priorities.
Study Start Date
December 21, 2020 (Actual)
Primary Completion Date
October 24, 2022 (Actual)
Study Completion Date
October 24, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
To assess the safety, tolerability and determine recommended phase 2 dose (RP2D) of GSK3845097 in HLA-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 positive participants with New York esophageal squamous cell carcinoma (NY-ESO)-1 and/or Cancer testis antigen 2 (LAGE-1a) positive, previously treated, advanced (metastatic or unresectable) Synovial Sarcoma (SS) and Myxoid/Round Cell Liposarcoma (MRCLS).
Detailed Description
This study is a substudy of the Master record - (209012) NCT04526509.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neoplasms
Keywords
Adoptive T-cell therapy, Advanced synovial sarcoma, Advanced Myxoid/Round Cell Liposarcoma, Advanced tumors, GSK3845097, T cell receptor, Leukapheresis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GSK3845097
Arm Type
Experimental
Arm Description
Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive high dose of GSK3845097 after completing lymphodepleting chemotherapy. The first study participant receiving GSK3845097 will receive the total assigned dose as 2 separate infusions 7 days apart, in aliquots of 30% (first infusion) and 70% (second infusion) of the total target dose , respectively. Based on the dose limiting toxicities reported in the first participant, then all subsequent participants treated with GSK3845097 will receive the full dose as a single, i.e., one-time, infusion.
Intervention Type
Drug
Intervention Name(s)
GSK3845097
Intervention Description
GSK3845097 was administered.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Cyclophosphamide was administered as lymphodepleting chemotherapy.
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Fludarabine was administered as lymphodepleting chemotherapy.
Primary Outcome Measure Information:
Title
Number of Participants with Dose Limiting Toxicities (DLTs)
Time Frame
Up to approximately 21 months
Title
Number of Participants with Adverse Events (AEs), Serious AEs and Adverse Events of Special Interest (AESI) based on Severity
Time Frame
Up to approximately 21 months
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR) assessed by investigator according to RECIST v1.1
Description
Overall response rate was 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.
Time Frame
Up to approximately 21 months
Title
Duration of Response (DoR)
Description
Duration of response was 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.
Time Frame
Up to approximately 21 months
Title
Maximum transgene expansion (Cmax)
Time Frame
Up to approximately 21 months
Title
Time to Cmax (Tmax)
Time Frame
Up to approximately 21 months
Title
Area under the concentration time curve from zero to time t AUC(0-t)
Time Frame
Up to approximately 21 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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. 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06504
Country
United States
Facility Name
GSK Investigational Site
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
GSK Investigational Site
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
GSK Investigational Site
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
GSK Investigational Site
City
Westwood
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
GSK Investigational Site
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
GSK Investigational Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
GSK Investigational Site
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
GSK Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
GSK Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
GSK Investigational Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
GSK Investigational Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
GSK Investigational Site
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3000
Country
Australia
Facility Name
GSK Investigational Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
GSK Investigational Site
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada
Facility Name
GSK Investigational Site
City
Muenchen
State/Province
Bayern
ZIP/Postal Code
81377
Country
Germany
Facility Name
GSK Investigational Site
City
Hannover
State/Province
Niedersachsen
ZIP/Postal Code
30625
Country
Germany
Facility Name
GSK Investigational Site
City
Koeln
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
50937
Country
Germany
Facility Name
GSK Investigational Site
City
Dresden
State/Province
Sachsen
ZIP/Postal Code
01307
Country
Germany
Facility Name
GSK Investigational Site
City
Amsterdam
ZIP/Postal Code
1066 CX
Country
Netherlands
Facility Name
GSK Investigational Site
City
Stockholm
ZIP/Postal Code
SE-171 64
Country
Sweden

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
IPD Sharing Time Frame
Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
IPD Sharing Access Criteria
Anonymized IPD is shared with researchers whose proposals are approved by an 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 may be granted, when justified, for up to 6 months.
IPD Sharing URL
http://www.gsk.com/en-gb/innovation/trials/data-transparency/

Learn more about this trial

Study of GSK3845097 in Previously Treated Participants With Advanced Synovial Sarcoma and Myxoid/Round Cell Liposarcoma

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