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

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

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

Study Overview

• Status: Terminated
• Conditions: Neoplasms
• Intervention / Treatment: Drug: GSK3901961; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: GSK3845097; Drug: GSK4427296

Detailed 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).

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • GSK Investigational Site
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • GSK Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • GSK Investigational Site
• Germany
  • Bayern
    • Muenchen, Bayern, Germany, 81377
      • GSK Investigational Site
  • Nordrhein-Westfalen
    • Koeln, Nordrhein-Westfalen, Germany, 50937
      • GSK Investigational Site
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • GSK Investigational Site
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • GSK Investigational Site
• Sweden
  • Stockholm, Sweden, SE-171 64
    • GSK Investigational Site
• United States
  • Florida
    • Jacksonville, Florida, United States, 32224
      • GSK Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • GSK Investigational Site
  • Kansas
    • Westwood, Kansas, United States, 66205
      • GSK Investigational Site
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • GSK Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • GSK Investigational Site
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • GSK Investigational Site
  • New York
    • New York, New York, United States, 10032
      • GSK Investigational Site
    • New York, New York, United States, 10065
      • GSK Investigational Site
  • Texas
    • Houston, Texas, United States, 77030
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Substudy 1: Cohort 1 - GSK3901961 in previously treated metastatic NSCLC; Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK3901961, as intravenous (IV) infusion after completing lymphodepleting chemotherapy.	Drug: GSK3901961; GSK3901961 as an IV infusion.; Drug: Cyclophosphamide; Cyclophosphamide will be used as lymphodepleting chemotherapy and will be administered via IV route.; Drug: Fludarabine; Fludarabine will be used as lymphodepleting chemotherapy and will be administered via IV route.
Experimental: Substudy 1: Cohort 2 - GSK3901961 in previously treated advanced SS or MRCLS; Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK3901961, as IV infusion after completing lymphodepleting chemotherapy.	Drug: GSK3901961; GSK3901961 as an IV infusion.; Drug: Cyclophosphamide; Cyclophosphamide will be used as lymphodepleting chemotherapy and will be administered via IV route.; Drug: Fludarabine; Fludarabine will be used as lymphodepleting chemotherapy and will be administered via IV route.
Experimental: Substudy 2: GSK3845097 in previously treated advanced SS or MRCLS; Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK3845097, as IV infusion after completing lymphodepleting chemotherapy.	Drug: Cyclophosphamide; Cyclophosphamide will be used as lymphodepleting chemotherapy and will be administered via IV route.; Drug: Fludarabine; Fludarabine will be used as lymphodepleting chemotherapy and will be administered via IV route.; Drug: GSK3845097; GSK3845097 as an IV infusion.
Experimental: Substudy 3: GSK4427296 in previously treated advanced SS or MRCLS; Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK4427296, as IV infusion after completing lymphodepleting chemotherapy.	Drug: Cyclophosphamide; Cyclophosphamide will be used as lymphodepleting chemotherapy and will be administered via IV route.; Drug: Fludarabine; Fludarabine will be used as lymphodepleting chemotherapy and will be administered via IV route.; Drug: GSK4427296; GSK4427296 as an IV infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Enrolled Across Sub Studies	Number of Participants Randomized across sub studies are presented.	Day -7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Substudy 1, 2 and 3: Overall response rate (ORR)	Overall response rate is 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.	Until disease progression (up to 4 years)
Substudy 1, 2 and 3: Duration of response (DOR)	Duration of response is 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.	Until disease progression (up to 4 years)
Substudy 1, 2 and 3: Maximum expansion/persistence (Cmax)	Whole blood samples will be collected at indicated time points for evaluation of Cmax.	Until disease progression (up to 4 years)
Substudy 1, 2 and 3 : Time to Cmax (Tmax)	Whole blood samples will be collected at indicated time points for evaluation of Tmax.	Until disease progression (up to 4 years)
Substudy 1, 2 and 3: Area under the concentration/persistence time curve from zero to time t (AUC[0-t])	Whole blood samples will be collected at indicated time points for evaluation of AUC (0 to t).	Until disease progression (up to 4 years)

Collaborators and Investigators

• Sponsor: Adaptimmune
• Investigators: Principal Investigator: Adaptimmune Patient Enquiries, Adaptimmune

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2020
• Primary Completion (Actual): June 8, 2023
• Study Completion (Actual): June 8, 2023

Study Registration Dates

• First Submitted: August 21, 2020
• First Submitted That Met QC Criteria: August 21, 2020
• First Posted (Actual): August 25, 2020

Study Record Updates

• Last Update Posted (Estimated): November 26, 2024
• Last Update Submitted That Met QC Criteria: November 8, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Leukapheresis; Advanced tumors; Adoptive T-cell therapy; Advanced synovial sarcoma; Advanced non-small cell lung cancer; GSK3845097; GSK3901961; GSK4427296; T cell receptors; Advanced myxoid/round cell liposarcoma
• Additional Relevant MeSH Terms: Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine
• Other Study ID Numbers: 209012; 2019-004446-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No