Master Protocol to Assess Safety and Dose of First Time in Human Next Generation Engineered T Cells in NY-ESO-1 and/or LAGE-1a Positive Advanced Solid Tumors

Neoplasms Clinical Trial

Official title:

Master Protocol to Assess the Safety and Recommended Phase 2 Dose of Next Generations of Autologous Enhanced NY-ESO-1/ LAGE-1a TCR Engineered T-cells, Alone or in Combination With Other Agents, in Participants With Advanced Tumors

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04526509
• Other study ID #: 209012
• Secondary ID: 2019-004446-14
• Status: Terminated
• Phase: Phase 1
• Start date: December 21, 2020
• Est. completion date: June 8, 2023

Study information

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

Clinical Trial Summary

This trial will evaluate the safety and efficacy of first time in human engineered T-cell therapies, in participants with advanced tumors.

Description:

This study is a master protocol. It has two sub studies registered as 209012 Sub Study 1 (NCT06048705) and 209012 Sub Study 2 (NCT05943990).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: June 8, 2023
• Est. primary completion date: June 8, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Additional criteria for participants with SS/ MRCLS:

• 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

Additional criteria for participants with non-small cell lung cancer (NSCLC):

• Participant has Stage IV NSCLC as confirmed by histology or cytology
• Prior therapies for participants lacking actionable genetic aberrations (i.e., wild type), per National Comprehensive Cancer Network (NCCN) guidelines: participant has been previously treated with or is intolerant to programmed death receptor-1 (PD)-1/Programmed death ligand 1 (PD-L1) checkpoint blockade therapy and has been previously treated with or is intolerant to a platinum-based chemotherapy. Adjuvant therapy will count as a regimen if completed within 6 months before relapse. Or for participants that harbors an actionable genetic aberration (e.g. BRAF, anaplastic lymphoma kinase [ALK]/ c-ros oncogene 1 [ROS1] etc.), per NCCN guidelines: participants has been previously treated with or is intolerant to SOC therapy, including targeted therapy, as recommended by NCCN or equivalent country-level guidelines (European Society for Medical Oncology [ESMO], National Institute for Health & Care Excellence [NICE]) . Or Investigator has decided that additional lines of SOC therapy after the first line are not in the participant's best interest.

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

• Neoplasms

Intervention

Drug:
• GSK3901961
GSK3901961 as an IV infusion.
• GSK3845097
GSK3845097 as an IV infusion.
• GSK4427296
GSK4427296 as an IV infusion.
• Cyclophosphamide
Cyclophosphamide will be used as lymphodepleting chemotherapy and will be administered via IV route.
• Fludarabine
Fludarabine will be used as lymphodepleting chemotherapy and will be administered via IV route.

Locations

Country	Name	City	State
Australia	GSK Investigational Site	Melbourne	Victoria
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Toronto	Ontario
Germany	GSK Investigational Site	Dresden	Sachsen
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 York	New York
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Saint Louis	Missouri
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 Enrolled Across Sub Studies	Number of Participants Randomized across sub studies are presented.	Day -7