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

Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05943990
• Other study ID #: 209012 Substudy 2
• Secondary ID: 2019-004446-14
• Status: Terminated
• Phase: Phase 1
• Start date: December 21, 2020
• Est. completion date: October 24, 2022

Study information

• Verified date: September 2023
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

This study is a substudy of the Master record - (209012) NCT04526509.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: October 24, 2022
• Est. primary completion date: October 24, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Liposarcoma
• Liposarcoma, Myxoid
• Neoplasms
• Sarcoma
• Sarcoma, Synovial

Intervention

Drug:
• GSK3845097
GSK3845097 was administered.
• Cyclophosphamide
Cyclophosphamide was administered as lymphodepleting chemotherapy.
• Fludarabine
Fludarabine was administered as lymphodepleting chemotherapy.

Locations

Country	Name	City	State
Australia	GSK Investigational Site	Melbourne	Victoria
Canada	GSK Investigational Site	Montréal	Quebec
Canada	GSK Investigational Site	Toronto	Ontario
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Hannover	Niedersachsen
Germany	GSK Investigational Site	Koeln	Nordrhein-Westfalen
Germany	GSK Investigational Site	Muenchen	Bayern
Netherlands	GSK Investigational Site	Amsterdam
Sweden	GSK Investigational Site	Stockholm
United States	GSK Investigational Site	Atlanta	Georgia
United States	GSK Investigational Site	Baltimore	Maryland
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Jacksonville	Florida
United States	GSK Investigational Site	Lexington	Kentucky
United States	GSK Investigational Site	New Haven	Connecticut
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Saint Louis	Missouri
United States	GSK Investigational Site	Tampa	Florida
United States	GSK Investigational Site	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Germany,  Netherlands,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Dose Limiting Toxicities (DLTs)	DLT events were graded according to NCI-CTCAE v5.0. DLTs were defined as Grade (Gr) 4 (life-threatening and death) related to GSK3845097 2) Gr 3 (Severe or medically significant) at least possibly related to GSK3845097 and do not resolve to Gr <=1 (or Baseline) within 7 days from the onset of the event 3) Gr >=3 non-infectious pneumonitis not responding to oxygen supplementation and systemic steroid treatment 4) Any Gr 3 cytokine release syndrome (CRS) at least possibly related to GSK3845097 that does not improve to Gr <2 (moderate) toxicity within 7 days with or without dexamethasone 5) Any Gr 4 CRS at least possibly related to study product that does not improve to Gr <=2 (or Baseline) within 7 days 6) Any Gr 3 or greater neurotoxicity that does not resolve to Gr <=2 within 72 hours 7) Any Gr >=3 organ toxicity (exclusive of CRS toxicity) involving major organ systems that persists for >72 hours and occurs within 28 days of infusion.	Up to 28 days
Primary	Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs Based on Maximum Severity	An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any untoward medical occurrence that, at any dose can result in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth or is medically significant or requires intervention to prevent one or the outcomes listed above. AEs and SAEs were graded according to NCI-CTCAE v5.0. Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe or medically significant but not immediately life-threatening; Grade 4- Life-threatening consequences; Grade 5- Death related to AE. AEs which start or worsen on or after T-cell infusion are classified as treatment emergent. SAEs are subset of AEs. Results for maximum severity grades has been presented.	Up to approximately 21 months
Primary	Number of Participants With Treatment Emergent Adverse Events of Special Interest (AESI)	An AESI may be of scientific and medical concern related to the treatment, monitored, and rapidly communicated by investigator to sponsor. AESIs included events of Cytokine Release Syndrome (CRS), Haematopoietic cytopenias (including pancytopenia and aplastic anaemia), Graft versus Host Disease (GvHD), Immune Effector-Cell Associated Neurotoxicity Syndrome (ICANS), Guillain-Barre Syndrome (GBS), Pneumonitis and treatment-related inflammatory response at tumor site(s) and Neutropenia Grade 4 lasting more than or equal to 28 days. AEs which start or worsen on or after T-cell infusion are classified as treatment emergent.	Up to approximately 21 months
Secondary	Overall Response Rate (ORR) Assessed by Investigator According to RECIST v1.1	Overall response rate (ORR) defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) via investigator assessment per Response Evaluation Criteria in Solid Tumors Criteria (RECIST) version 1.1 relative to the total number of participants in the analysis population. Partial response (PR) was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response (CR) was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters (mm). Confidence intervals (CI) were calculated using the exact (Clopper-Pearson) method.	Up to approximately 21 months
Secondary	Duration of Response (DoR)	DoR is defined as the interval of time (in months) from first documented evidence of the confirmed response (PR or CR) as assessed by local investigators to the date of disease progression per RECIST v1.1 or death due to any cause, among participants with a confirmed response of PR or CR. PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.	Up to approximately 21 months
Secondary	Maximum Transgene Expansion (Cmax) of GSK3845097	Cmax was defined as peak cell expansion during the interventional phase. Blood samples were collected to measure Cmax.	Up to 21 days
Secondary	Time to Cmax (Tmax) of GSK3845097	Tmax was defined as time to peak cell expansion during the interventional phase. Blood samples were collected to measure Tmax.	Up to 21 days
Secondary	Area Under the Time Curve From Zero to Time 28 Days (AUC[0-28])	Area under the cell expansion-time curve from first T-cell infusion to Day 28. Blood samples were collected to measure AUC (0-28 days).	Up to 28 days