Description:
This trial will evaluate the safety and efficacy of first time in human engineered T-cell
therapies, in participants with advanced tumors.
Title
- Brief Title: Master Protocol to Assess the 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
- 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 IDs
- ORG STUDY ID:
209012
- NCT ID:
NCT04526509
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| GSK3901961 | | Substudy 1: GSK3901961 in previously treated advanced SS |
| GSK3845097 | | Substudy 2: GSK3845097 in previously treated advanced SS |
| Fludarabine | | Substudy 1: GSK3901961 in previously treated advanced SS |
| Cyclophosphamide | | Substudy 1: GSK3901961 in previously treated advanced SS |
Purpose
This trial will evaluate the safety and efficacy of first time in human engineered T-cell
therapies, in participants with advanced tumors.
Detailed Description
New York esophageal antigen-1 (NY-ESO-1) and LAGE-1a antigens are tumor-associated proteins
that have been found in several tumor types. Clinical trials using adoptively transferred
T-cells directed against NY-ESO-1 have shown objective responses. GSK3901961 and GSK3845097
are next generation engineered TCR T-cells, co-expressing the CD8α cell surface receptor,
targeting NY-ESO-1, and co-expressing the dnTGF-βRII cell surface receptor, targeting
NY-ESO-1, respectively to potentially improve function. This is a master protocol evaluating
first time in human T-cell therapies. It will initially consist of two independent
substudies, investigating GSK3901961 and GSK3845097 in HLA*A02+ participants with NYESO1+
previously treated advanced (metastatic or unresectable) synovial sarcoma (SS) and/or
previously treated metastatic non-small cell lung cancer (NSCLC).
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Substudy 1: GSK3901961 in previously treated advanced SS | Experimental | Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK3901961, as a single intravenous (IV) infusion after completing lymphodepleting chemotherapy. | - GSK3901961
- Fludarabine
- Cyclophosphamide
|
| Substudy 1: GSK3901961 in previously treated metastatic NSCLC | Experimental | Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK3901961, as a single IV infusion after completing lymphodepleting chemotherapy. | - GSK3901961
- Fludarabine
- Cyclophosphamide
|
| Substudy 2: GSK3845097 in previously treated advanced SS | Experimental | Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK3845097, as a single IV infusion after completing lymphodepleting chemotherapy. | - GSK3845097
- Fludarabine
- Cyclophosphamide
|
Eligibility Criteria
Eligibility Criteria: Inclusion criteria:
- Participant must be >=18 years of age on the day of signing informed consent.
- Participant must be positive for Human leukocyte antigen (HLA)-A*02:01, HLA-A*02:05,
and/or HLA-A*02:06 alleles
- Participant's tumor is positive for NY-ESO-1 expression by a designated central
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 synovial sarcoma
- Participant has advanced (metastatic or unresectable) synovial sarcoma confirmed by
histology.
- Participant has received/completed treatment with anthracycline or anthracycline with
ifosfamide for advanced (metastatic or inoperable) disease and progressed.
Additional criteria for participants with non-small cell lung cancer (NSCLC):
- Participant has Stage IV NSCLC as confirmed by histology or cytology.
- Participant has been previously treated with or is intolerant to programmed death
receptor-1 (PD)-1/Programmed cell death ligand 1 (PD-L1) checkpoint blockade therapy
and doublet taxane & platinum chemotherapy.
Exclusion criteria:
- Central nervous system metastases, except in rare cases of 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.
- Previous NY-ESO-1 vaccine or NY-ESO-1 targeting antibody.
- Prior gene therapy using an integrating vector.
- Previous allogeneic hematopoietic stem cell transplant.
- Washout periods for prior radiotherapy and systemic chemotherapy must be followed.
- Major surgery <=28 days of first dose of study intervention.
- For participants with NSCLC that harbors an actionable genetic aberration, e.g. BRAF,
anaplastic lymphoma kinase (ALK)/ c-ros oncogene 1 (ROS1) or others, has received and
failed >=3 lines of systemic therapy.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Substudy 1 and 2: Frequency of dose limiting toxicities (DLTs) according to severity. |
| Time Frame: | Until disease progression (up to 4 years) |
| Safety Issue: | |
| Description: | Toxicities will be considered DLTs if they are considered at least possibly related to transduced T-cells; and they occur within the DLT-assessment period. Severity will be summarized using National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 5.0 |
Secondary Outcome Measures
| Measure: | Substudy 1 and 2: Overall response rate (ORR) |
| Time Frame: | Until disease progression (up to 4 years) |
| Safety Issue: | |
| Description: | 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 analysis population at any time per Response evaluation criteria in solid tumors (RECIST) version 1.1 as determined by the local investigators. |
| Measure: | Substudy 1 and 2: Duration of response (DOR) |
| Time Frame: | Until disease progression (up to 4 years) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Substudy 2: Progression free survival (PFS) |
| Time Frame: | Until disease progression (up to 4 years) |
| Safety Issue: | |
| Description: | Progression free survival is defined as the time from the date of T-cell infusion until first documented sign of disease progression, RECIST 1.1 or death. |
| Measure: | Substudy 2: Disease control rate (DCR) |
| Time Frame: | Until disease progression (up to 4 years) |
| Safety Issue: | |
| Description: | Disease control rate is defined as the percentage of participants with a confirmed CR, PR, or stable disease (SD) with minimal 12 weeks duration relative to the total number of participants within the analysis population at any time per RECIST version 1.1 as determined by the local investigators. |
| Measure: | Substudy 2: Time to response |
| Time Frame: | Until disease progression (up to 4 years) |
| Safety Issue: | |
| Description: | Time to response is defined as time from date of T-cell infusion to first documented evidence of confirmed CR and PR (RECIST version 1.1). |
| Measure: | Substudy 1 and 2: Maximum expansion/persistence (Cmax) |
| Time Frame: | Until disease progression (up to 4 years) |
| Safety Issue: | |
| Description: | Whole blood samples will be collected at indicated time points for evaluation of Cmax. |
| Measure: | Substudy 1 and 2: Time to Cmax (Tmax) |
| Time Frame: | Until disease progression (up to 4 years) |
| Safety Issue: | |
| Description: | Whole blood samples will be collected at indicated time points for evaluation of Tmax. |
| Measure: | Substudy 1 and 2: Area under the concentration/persistence time curve from zero to time t (AUC[0-t]) |
| Time Frame: | Until disease progression (up to 4 years) |
| Safety Issue: | |
| Description: | Whole blood samples will be collected at indicated time points for evaluation of AUC (0 to t). |
| Measure: | Substudy 1 and 2: Phenotype of transduced T cells |
| Time Frame: | Until disease progression (up to 4 years) |
| Safety Issue: | |
| Description: | Tumor samples will be collected to assess phenotype of transduced T cells. |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | GlaxoSmithKline |
Trial Keywords
- Adoptive T-cell therapy
- Advanced synovial sarcoma
- Advanced non-small cell lung cancer
- Advanced tumors
- GSK3845097
- GSK3901961
- T cell receptors
- Leukapheresis
Last Updated
May 7, 2021
