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

NCT ID: NCT04526509

Last Updated: 2024-11-26

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-12-21

Study Completion Date

2023-06-08

Brief Summary

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

Detailed Description

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

Conditions

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Neoplasms

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

This will be an open-label study. Hence, there will be no masking

Study Groups

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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.

Group Type EXPERIMENTAL

GSK3901961

Intervention Type DRUG

GSK3901961 as an IV infusion.

Cyclophosphamide

Intervention Type DRUG

Cyclophosphamide will be used as lymphodepleting chemotherapy and will be administered via IV route.

Fludarabine

Intervention Type DRUG

Fludarabine will be used as lymphodepleting chemotherapy and will be administered via IV route.

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.

Group Type EXPERIMENTAL

GSK3901961

Intervention Type DRUG

GSK3901961 as an IV infusion.

Cyclophosphamide

Intervention Type DRUG

Cyclophosphamide will be used as lymphodepleting chemotherapy and will be administered via IV route.

Fludarabine

Intervention Type DRUG

Fludarabine will be used as lymphodepleting chemotherapy and will be administered via IV route.

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.

Group Type EXPERIMENTAL

GSK3845097

Intervention Type DRUG

GSK3845097 as an IV infusion.

Cyclophosphamide

Intervention Type DRUG

Cyclophosphamide will be used as lymphodepleting chemotherapy and will be administered via IV route.

Fludarabine

Intervention Type DRUG

Fludarabine will be used as lymphodepleting chemotherapy and will be administered via IV route.

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.

Group Type EXPERIMENTAL

GSK4427296

Intervention Type DRUG

GSK4427296 as an IV infusion.

Cyclophosphamide

Intervention Type DRUG

Cyclophosphamide will be used as lymphodepleting chemotherapy and will be administered via IV route.

Fludarabine

Intervention Type DRUG

Fludarabine will be used as lymphodepleting chemotherapy and will be administered via IV route.

Interventions

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GSK3901961

GSK3901961 as an IV infusion.

Intervention Type DRUG

GSK3845097

GSK3845097 as an IV infusion.

Intervention Type DRUG

GSK4427296

GSK4427296 as an IV infusion.

Intervention Type DRUG

Cyclophosphamide

Cyclophosphamide will be used as lymphodepleting chemotherapy and will be administered via IV route.

Intervention Type DRUG

Fludarabine

Fludarabine will be used as lymphodepleting chemotherapy and will be administered via IV route.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Adaptimmune

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Adaptimmune Patient Enquiries

Role: PRINCIPAL_INVESTIGATOR

Adaptimmune

Locations

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GSK Investigational Site

Jacksonville, Florida, United States

Site Status

GSK Investigational Site

Atlanta, Georgia, United States

Site Status

GSK Investigational Site

Westwood, Kansas, United States

Site Status

GSK Investigational Site

Lexington, Kentucky, United States

Site Status

GSK Investigational Site

Baltimore, Maryland, United States

Site Status

GSK Investigational Site

St Louis, Missouri, United States

Site Status

GSK Investigational Site

New York, New York, United States

Site Status

GSK Investigational Site

New York, New York, United States

Site Status

GSK Investigational Site

Houston, Texas, United States

Site Status

GSK Investigational Site

Melbourne, Victoria, Australia

Site Status

GSK Investigational Site

Toronto, Ontario, Canada

Site Status

GSK Investigational Site

Montreal, Quebec, Canada

Site Status

GSK Investigational Site

Munich, Bavaria, Germany

Site Status

GSK Investigational Site

Cologne, North Rhine-Westphalia, Germany

Site Status

GSK Investigational Site

Dresden, Saxony, Germany

Site Status

GSK Investigational Site

Amsterdam, , Netherlands

Site Status

GSK Investigational Site

Stockholm, , Sweden

Site Status

Countries

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United States Australia Canada Germany Netherlands Sweden

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2019-004446-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

209012

Identifier Type: -

Identifier Source: org_study_id

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