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

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Primary Purpose

Status

Terminated

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

GSK3845097

Cyclophosphamide

Fludarabine

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

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

NCT ID

NCT05943990

First Posted

July 5, 2023

Last Updated

July 5, 2023

Sponsor

GlaxoSmithKline

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/

Neoplasms

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial