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

Study Overview
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Brief Summary
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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
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This study is a substudy of the Master record - (209012) NCT04526509.

Official Title
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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

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: GSK3845097
* Drug: Cyclophosphamide
* Drug: Fludarabine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK3845097<br>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. | Drug: GSK3845097<br>* GSK3845097 was administered.<br>Drug: Cyclophosphamide<br>* Cyclophosphamide was administered as lymphodepleting chemotherapy.<br>Drug: Fludarabine<br>* Fludarabine was administered as lymphodepleting chemotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Dose Limiting Toxicities (DLTs) |  | Up to approximately 21 months | 
| Number of Participants with Adverse Events (AEs), Serious AEs and Adverse Events of Special Interest (AESI) based on Severity |  | Up to approximately 21 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to approximately 21 months | 
| 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. | Up to approximately 21 months | 
| Maximum transgene expansion (Cmax) |  | Up to approximately 21 months | 
| Time to Cmax (Tmax) |  | Up to approximately 21 months | 
| Area under the concentration time curve from zero to time t AUC(0-t) |  | Up to approximately 21 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adoptive T-cell therapy, Advanced synovial sarcoma, Advanced Myxoid/Round Cell Liposarcoma, Advanced tumors, GSK3845097, T cell receptor, Leukapheresis