Master Protocol to Assess the Safety and Antitumor Activity of Genetically Engineered T Cells in NY-ESO-1 and/or LAGE-1a Positive Solid Tumors (IGNYTE-ESO)
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| ClinicalTrials.gov Identifier: NCT03967223 |
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Recruitment Status :
Active, not recruiting
First Posted : May 30, 2019
Last Update Posted : April 25, 2024
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Sponsor:
Adaptimmune
Information provided by (Responsible Party):
Adaptimmune
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Brief Summary:
This trial will evaluate safety and efficacy of human engineered T-cell therapies, in participants with advanced tumors.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Neoplasms | Drug: Letetresgene autoleucel (lete-cel, GSK3377794) Drug: Fludarabine Drug: Cyclophosphamide | Phase 2 |
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/LAGE-1a have shown objective responses. Letetresgene autoleucel (lete-cel, GSK3377794) is the first generation of NY-ESO-1 specific T-cell receptor engineered T cells. This is a master protocol investigating T-cell therapies. It will initially consist of a core protocol with two independent substudies investigating Letetresgene autoleucel in previously untreated (1L) Human Leukocyte Antigen (HLA)-A*02+ participants with NY-ESO-1+ advanced (metastatic or unresectable) synovial sarcoma (SS) or myxoid/round cell liposarcoma (MRCLS) (Substudy 1) and Letetresgene autoleucel as second line or higher (2L+) treatment in HLA-A*02+ participants with NY-ESO-1+ advanced (metastatic or unresectable) SS or MRCLS who have progressed following treatment with anthracycline based chemotherapy (Substudy 2).
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 103 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Masking Description: | This will be an open-label study. Hence, there will be no masking. |
| Primary Purpose: | Treatment |
| Official Title: | Master Protocol to Assess the Safety and Antitumor Activity of Genetically Engineered NY-ESO-1-Specific (c259) T Cells, Alone or in Combination With Other Agents, in HLA-A2+ Participants With NY-ESO-1 and/or LAGE-1a Positive Solid Tumors (IGNYTE-ESO) |
| Actual Study Start Date : | December 31, 2019 |
| Estimated Primary Completion Date : | August 28, 2024 |
| Estimated Study Completion Date : | July 31, 2026 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Substudy 1: lete-cel in previously untreated advanced (metastatic or unresectable) SS or MRCLS
Eligible participants will be leukapheresed to manufacture engineered T cells. Participants will then receive letetresgene autoleucel.
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Drug: Letetresgene autoleucel (lete-cel, GSK3377794)
letetresgene autoleucel will be administered. Drug: Fludarabine Fludarabine will be used as the lymphodepleting chemotherapy Drug: Cyclophosphamide Cyclophosphamide will be used as the lymphodepleting chemotherapy. |
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Experimental: Substudy 2: lete-cel in advanced (metastatic or unresectable) SS or MRCLS post anthracycline chemo
Eligible participants will be leukapheresed to manufacture engineered T cells. Participants will then receive letetresgene autoleucel.
|
Drug: Letetresgene autoleucel (lete-cel, GSK3377794)
letetresgene autoleucel will be administered. Drug: Fludarabine Fludarabine will be used as the lymphodepleting chemotherapy Drug: Cyclophosphamide Cyclophosphamide will be used as the lymphodepleting chemotherapy. |
Primary Outcome Measures :
- Substudy 1: Overall response rate (ORR) [ Time Frame: Until disease progression (up to 5 years) ]Overall response rate is defined as the percentage of participants with a confirmed complete response (CR) or 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 (v) 1.1. as determined by the local investigators.
- Substudy 2: Overall response rate (ORR) as assessed by central independent review [ Time Frame: Up to 5 years ]Overall response rate is defined as the percentage of participants with a confirmed CR or PR relative to the total number of participants within the analysis population at any time per RECIST v1.1. as assessed by central independent review.
Secondary Outcome Measures :
- Substudy 1 and 2: Time to response (TTR) [ Time Frame: Until disease progression (up to 5 years) ]Time to response is defined as time from date of T-cell administration to first documented evidence of confirmed (CR or PR) as assessed by local investigators per RECIST v1.1.
- Substudy 1 and 2: Duration of response (DOR) [ Time Frame: Until disease progression (up to 5 years) ]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.
- Substudy 1 and 2: Disease control rate (DCR) [ Time Frame: Until disease progression (up to 5 years) ]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 the time of primary analysis as determined by Investigators per RECIST v1.1.
- Substudy 1 and 2: Progression free survival (PFS) [ Time Frame: Until disease progression (up to 5 years) ]Progression free survival is defined as the time from the date of T-cell administration until first documented sign of disease progression per RECIST v1.1, or death.
- Substudy 1 and 2: Frequency of adverse events (AEs), serious adverse events (SAEs) and AEs of special interest (AESI) according to severity [ Time Frame: Until disease progression (up to 5 years) ]AEs, SAEs and AESIs will be collected. Severity of AEs and SAEs will be summarized using National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.
- Substudy 1 and 2: Number of participants with replication competent lentivirus (RCL) [ Time Frame: Until disease progression (up to 5 years) ]RCL exposure will be assessed by polymerase chain reaction (PCR) based assay.
- Substudy 1 and 2: Number of participants with insertional oncogenesis (IO) [ Time Frame: Until disease progression (up to 5 years) ]Peripheral blood mononuclear cells (PBMC) samples will be collected for monitoring insertional oncogenesis by PCR for gene modified cells in the blood.
- Substudy 2: Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis parameters [ Time Frame: Until disease progression (up to 5 years) ]Blood and urine samples will be collected for assessment of hematology, clinical chemistry and urinalysis parameters.
- Substudy 1 and 2: Maximum transgene expansion (Cmax) of letetresgene autoleucel [ Time Frame: Until disease progression (up to 5 years) ]Whole blood samples will be collected at indicated time points for evaluation of Cmax.
- Substudy 1 and 2: Time to Cmax (Tmax) of letetresgene autoleucel [ Time Frame: Until disease progression (up to 5 years) ]Whole blood samples will be collected at indicated time points for evaluation of Tmax.
- Substudy 1 and 2: Area under the concentration/persistence time curve from zero to time t (AUC[0-t]) of letetresgene autoleucel [ Time Frame: Until disease progression (up to 5 years) ]Whole blood samples will be collected at indicated time points for evaluation of AUC(0-t).
- Substudy 2: Overall response rate (ORR) as determined by the local investigators [ Time Frame: Up to 5 years ]Overall response rate is defined as the percentage of participants with a confirmed CR or PR relative to the total number of participants within the analysis population at any time per RECIST v1.1. as determined by the local investigators.
- Substudy 2: Overall Survival (OS) [ Time Frame: Up to 5 years ]Overall Survival is defined as the interval of time between the date of T-cell infusion and the date of death.
- Substudy 2: Number of participants with positive anti-drug antibodies (ADA) and titers of ADA against letetresgene autoleucel [ Time Frame: Up to 36 months ]Serum samples will be collected to analyze for the presence of ADAs using validated immunoassays.
Information from the National Library of Medicine
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| Ages Eligible for Study: | 10 Years and older (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Participant must be greater than or equal to 10 years of age on the day of signing informed consent.
- Participant scheduled to receive clinical drug product supply must also weigh ≥40 kg
- Participant must be positive for HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 alleles by a designated central laboratory
- Participant's tumor is positive for NY-ESO-1 expression by a designated central laboratory.
- Participant has a diagnosis of synovial sarcoma (SS) or myxoid/round cell liposarcoma (MRCLS)
- Performance status: dependent on age - Lansky > 60, Karnofsky > 60, Eastern Cooperative Oncology Group 0-1.
- Participant must have adequate organ function and blood cell counts, within 7 days prior to leukapheresis.
- At time of treatment, participant has measurable disease according to RECIST v1.1.
- Male or female. Contraception requirements will apply at the time of leukapheresis and treatment.
- Consultation for prior history per protocol specifications.
Exclusion Criteria:
- Central nervous system metastases.
- Any other prior malignancy that is not in complete remission.
- Clinically significant systemic illness (Serious active infections or significant cardiac, pulmonary, hepatic or other organ dysfunction, that in the judgment of the Investigator would compromise the participant's ability to tolerate protocol therapy or significantly increase the risk of complications).
- Prior or active demyelinating disease.
- History of chronic or recurrent (within the last year prior to leukapheresis) severe autoimmune or immune mediated disease (e.g. Crohn's disease, systemic lupus) 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.
- Participant had major surgery in less than or equal to 28 days of first dose of study intervention.
- Prior radiation exceeds protocol specified limits.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03967223
Locations
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Sponsors and Collaborators
Adaptimmune
Investigators
| Study Director: | Adaptimmune | Adaptimmune |
| Responsible Party: | Adaptimmune |
| ClinicalTrials.gov Identifier: | NCT03967223 |
| Other Study ID Numbers: |
208467 |
| First Posted: | May 30, 2019 Key Record Dates |
| Last Update Posted: | April 25, 2024 |
| Last Verified: | April 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | IPD for this study will be made available via the Clinical Study Data Request site. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) Clinical Study Report (CSR) |
| 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. |
| 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. |
| URL: | http://clinicalstudydatarequest.com |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Adaptimmune:
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Adoptive T-cell therapy Advanced metastatic disease Advanced unresectable disease Synovial sarcoma Myxoid/round cell liposarcoma GSK3377794 |
Positive solid tumors T-cell receptors Leukapheresis Letetresgene autoleucel Lete-cel |
Additional relevant MeSH terms:
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Cyclophosphamide Fludarabine Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents |
Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists |