Clinical trial NCT05943990: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Neoplasms
Keywords: Adoptive T-cell therapy
Advanced synovial sarcoma
Advanced Myxoid/Round Cell Liposarcoma
Advanced tumors
GSK3845097
T cell receptor
Leukapheresis
Lead sponsor: Adaptimmune
Sponsor class: INDUSTRY
First posted: 2023-07-13
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Up to 28 days
measure: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs Based on Maximum Severity
timeFrame: Up to approximately 21 months
measure: Number of Participants With Treatment Emergent Adverse Events of Special Interest (AESI)
timeFrame: Up to approximately 21 months
Secondary outcomes:
measure: Overall Response Rate (ORR) Assessed by Investigator According to RECIST v1.1
timeFrame: Up to approximately 21 months
measure: Duration of Response (DoR)
timeFrame: Up to approximately 21 months
measure: Maximum Transgene Expansion (Cmax) of GSK3845097
timeFrame: Up to 21 days
measure: Time to Cmax (Tmax) of GSK3845097
timeFrame: Up to 21 days
measure: Area Under the Time Curve From Zero to Time 28 Days (AUC[0-28])
timeFrame: Up to 28 days
Other outcomes:
Locations:
city: New Haven
country: United States
facility: GSK Investigational Site
state: Connecticut
city: Jacksonville
country: United States
facility: GSK Investigational Site
state: Florida
city: Tampa
country: United States
facility: GSK Investigational Site
state: Florida
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Westwood
country: United States
facility: GSK Investigational Site
state: Kansas
city: Lexington
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
city: Saint Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Melbourne
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montréal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Koeln
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Dresden
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Amsterdam
country: Netherlands
facility: GSK Investigational Site
city: Stockholm
country: Sweden
facility: GSK Investigational Site
Study officials:
affiliation: Adaptimmune
name: Adaptimmune Patient Enquiries
role: PRINCIPAL_INVESTIGATOR
References: