Study of GSK3901961 In Previously Treated Advanced (Metastatic OR Unresectable) Synovial Sarcoma/ Myxoid/Round Cell Liposarcoma, and Previously Treated Metastatic Non-Small Cell Lung Cancer

Neoplasms Clinical Trial

Official title:

Assessment of Safety and Recommended Phase 2 Dose of Autologous T Cells Engineered With an Affinity-enhanced TCR Targeting NYESO1 and LAGE1a, and Co-expressing CD8α (GSK3901961) in Participants With NYESO1 and/or LAGE1a Positive Previously Treated Advanced (Metastatic or Unresectable) Synovial Sarcoma / Myxoid/Round Cell Liposarcoma; or NYESO1 and/or LAGE1a Positive Previously Treated Metastatic Non-Small Cell Lung Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT06048705
• Other study ID #: 209012 Substudy 1
• Status: Terminated
• Phase: Phase 1
• Start date: March 9, 2021
• Est. completion date: May 26, 2023

Study information

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

Clinical Trial Summary

The primary purpose of this sub study is to assess the safety, tolerability and determine recommended Phase 2 dose (RP2D) of GSK3901961 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 metastatic Non-Small Cell Lung Cancer (NSCLC) and previously treated, advanced (metastatic or unresectable) Synovial Sarcoma/ Myxoid/Round Cell Liposarcoma SS/MRCLS.

Description:

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: May 26, 2023
• Est. primary completion date: May 26, 2023
• 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
• Participant has histologically or cytologically confirmed Stage IV NSCLC
• Participant has been previously treated with SOC for Stage IV NSCLC

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

• Carcinoma, Non-Small-Cell Lung
• Liposarcoma
• Liposarcoma, Myxoid
• Lung Neoplasms
• Neoplasms
• Sarcoma
• Sarcoma, Synovial

Intervention

Drug:
• GSK3901961
GSK3901961 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)		Up to approximately 21 months
Primary	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	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
Secondary	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
Secondary	Maximum transgene expansion (Cmax)		Up to approximately 21 months
Secondary	Time to Cmax (Tmax)		Up to approximately 21 months
Secondary	Area Under the Time Curve From Zero to Time 28 Days AUC(0-28)		Up to 28 days