Overview
Sponsor-declared trial summary
Phase
Human pharmacology (Phase I) - Other
Status
Authorised, recruiting
Participants planned
71
Countries
3
Sites
3
Non-small cell lung cancer (NSCLC)
To monitor participants for delayed AEs associated with administration of autologous cells that have been genetically modified.
Key facts
- Sponsor
- Uswm Ct Llc
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years, 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 14 Sep 2020 → ongoing
- Decision date (initial)
- 2024-08-05
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
- Funding sources
- USWM CT, LLC
External identifiers
- EU CT number
- 2024-513033-21-00
- EudraCT number
- 2018-004888-31
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety
To monitor participants for delayed AEs associated with administration of autologous cells that have been genetically modified.
Secondary objectives 4
- To monitor Replication Competent Lentivirus (RCL)
- To measure persistence of genetically modified cells in the body
- Assess the pattern of vector integration sites if at least 1%of cells in the surrogate sample are positive for vector sequences by polymerase chain reaction (PCR)
- To monitor survival status
Conditions and MedDRA coding
Non-small cell lung cancer (NSCLC)
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | PT | 10042863 | Synovial sarcoma | 100000004864 |
| 20.0 | PT | 10073137 | Myxoid liposarcoma | 100000004864 |
| 21.0 | LLT | 10028228 | Multiple myeloma | 10029104 |
| 21.1 | PT | 10061873 | Non-small cell lung cancer | 100000004864 |
Regulatory references
- Plan to share IPD
- No
| EU CT number | Title | Sponsor |
|---|---|---|
| 2018-003949-42 | A Phase 1b/2a Pilot Randomized Study to Evaluate the Safety and Tolerability of Autologous T-Cells Expressing Enhanced TCRs (T-Cell Receptors) Specific for NY-ESO-1/LAGE-1a (GSK3377794) Alone, or in Combination with Pembrolizumab in HLA-A2+ Participants with NY-ESO-1- or LAGE-1a-Positive Advanced or Recurrent Non-Small Cell Lung Cancer, Estudio piloto y aleatorizado en fase 1b/2a para evaluar la seguridad y la tolerabilidad de linfocitos T autólogos que expresan RLT (receptores de linfocitos T) potenciados específicos de NY-ESO-1/LAGE1a (GSK3377794) solos o en combinación con pembrolizumab en pacientes HLA-A2+ con cáncer de pulmón no microcítico avanzado o recurrente con positividad de NY-ESO-1 o LAGE1a. | |
| 2024-513032-14-00 | 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) | Adaptimmune LLC |
| 2019-000415-87 | 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), Protocolo maestro para evaluar la seguridad y actividad antitumoral de linfocitos T específicos de NY-ESO-1 (c259) modificados genéticamente, en monoterapia o en combinación con otros fármacos, en participantes con HLA-A2+ que presentan tumores sólidos positivos para NY-ESO-1 y/o LAGE-1a (IGNITE-ESO), Protocollo master per valutare la sicurezza e l’attività antitumorale di cellule T NY-ESO-1-specifiche (c259) geneticamente modificate, in monoterapia o in associazione con altri agenti, in pazienti HLA-A2+ affetti da tumori solidi NY-ESO-1 e/o LAGE-1a positivi (IGNYTE-ESO), Protocollo master per valutare la sicurezza e l’attività antitumorale di cellule T NY-ESO-1-specifiche (c259) geneticamente modificate, in monoterapia o in associazione con altri agenti, in pazienti HLA-A2+ affetti da tumori solidi NY-ESO-1 e/o LAGE-1a positivi (IGNYTE-ESO) | |
| 2019-004446-14 | 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, Protocolo maestro para evaluar la seguridad y la dosis recomendada para la fase 2 de las siguientes generaciones de células T autólogas modificadas con TCR NY-ESO-1/LAGE-1a mejorados, en monoterapia o en combinación con otros agentes, en participantes con tumores avanzados. |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- 1. Participants who have received at least one dose of ADP adoptive cell therapy agent.
- 2. Participants who have completed ADP sponsored or supported interventional study or have withdrawn from it.
- 3. Participants who have completed treatment as part of managed access to an adoptive cell therapy.
- 4. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- 5. The investigator is responsible for review of medical history.
- 6. Capable of giving signed informed consent.
Exclusion criteria 1
- None
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 6
- AEs/SAEs to be reported: New malignancies
- AEs/SAEs to be reported: New incidence or exacerbation of a pre-existing neurologic disorder
- AEs/SAEs to be reported: New incidence or exacerbation of a prior rheumatologic or other autoimmune disorder
- AEs/SAEs to be reported: New incidence of hematologic disorder
- AEs/SAEs to be reported: New incidence of infection (potentially related to gene modified cell therapy)
- AEs/SAEs to be reported: Unanticipated illness and/or hospitalization deemed related to gene modified cell therapy
Secondary endpoints 4
- Vesicular Stomatitis Virus G protein (VSV-G) deoxyribonucleic acid (DNA) copies in peripheral blood samples.
- Woodchuck hepatitis virus posttranscriptional regulatory element (WPRE) or Psi DNA copies in peripheral blood samples
- Integrated vector sequences and vector integration patterns (e.g., polyclonal, oligoclonal, or monoclonal) identified in peripheral blood
- Incidence of death and time to death
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PRD10972984 · Product
- Active substance
- Letetresgene Autoleucel
- Pharmaceutical form
- INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 15.00 billion organisms billion organisms
- Max total dose
- 15.00 billion organisms billion organisms
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Not Authorised
- MA holder
- ADAPTIMMUNE LLC
- Paediatric formulation
- No
- Orphan designation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Uswm Ct Llc
- Sponsor organisation
- USWM Ct LLC
- Address
- 4441 Springdale Road
- City
- Louisville
- Postcode
- 40241-1086
- Country
- United States
Scientific contact point
- Organisation
- USWM Ct LLC
- Contact name
- Regulatory Affairs
Public contact point
- Organisation
- USWM Ct LLC
- Contact name
- Regulatory Affairs
Third parties 6
| Organisation | City, country | Duties |
|---|---|---|
| Bioclinica Inc. ORG-100033079
|
Princeton, United States | Other |
| Q Squared Solutions Limited ORG-100042527
|
Reading, United Kingdom | Other |
| Icon Clinical Research Limited ORG-100008322
|
Dublin 18, Ireland | On site monitoring, Code 11, Other, Code 5, Data management, E-data capture |
| Bioclinica Inc. ORG-100033079
|
Princeton, United States | Other |
| Bioagilytix Labs LLC ORG-100013030
|
Boston, United States | Other |
| Primevigilance Limited ORG-100027742
|
Guildford, United Kingdom | Other, Code 8 |
Locations
3 EU/EEA countries · 3 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Authorised, recruiting | 2 | 1 |
| Netherlands | Authorised, recruitment pending | 1 | 1 |
| Spain | Authorised, recruiting | 2 | 1 |
| Rest of world
Canada, United States, United Kingdom, Australia
|
— | 66 | — |
Investigational sites
Fondazione IRCCS Istituto Nazionale Dei Tumori
Department of Medical Oncology, Via Giacomo Venezian 1, 20133, Milan
Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
Division of Medical Oncology, Division of Molecular Oncology & Immunology, Plesmanlaan 121, 1066 CX, Amsterdam
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Italy | 2022-12-15 | ||||
| Spain | 2020-09-14 | ||||
| Netherlands |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 18 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_2024-513033-21-00_Redacted | 6.0 |
| Recruitment arrangements (for publication) | K1_ES_Recruitment Procedure | 1.0 |
| Recruitment arrangements (for publication) | K1_IT_Recruitment Procedure | 1.0 |
| Recruitment arrangements (for publication) | K1_NL_Recruitment Procedure | 1.0 |
| Subject information and informed consent form (for publication) | L1_ES_SIS-ICF_Main_Spanish_redacted | 11.0 |
| Subject information and informed consent form (for publication) | L1_ES_SIS-ICF_Pregnant Partner_Spanish_redacted | 8.0 |
| Subject information and informed consent form (for publication) | L1_ES_SIS-ICF_Third party_Spanish | 5.0 |
| Subject information and informed consent form (for publication) | L1_ES_SIS-ICF_Use of Photo Materials_Spanish | 6.0 |
| Subject information and informed consent form (for publication) | L1_IT_SIS-ICF_Main_Italian_redacted | 11.0 |
| Subject information and informed consent form (for publication) | L1_IT_SIS-ICF_Partner pregnancy_Italian_redacted | 6.0 |
| Subject information and informed consent form (for publication) | L1_IT_SIS-ICF_Photo Video_Italian | 9.0 |
| Subject information and informed consent form (for publication) | L1_NL_SIS-ICF_Main_Dutch_redacted | 9.0 |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_2024-513033-21-00 | 2.0 |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_2024-513033-21-00_Dutch | 2.0 |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_2024-513033-21-00_Italian | 2.0 |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_2024-513033-21-00_Spanish | 2.0 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_2024-513033-21-00_Italian | 5.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_2024-513033-21-00_Spanish | 6.0 |
Application history
6 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-06-12 | Spain | Acceptable with conditions 2024-07-11
|
2024-07-11 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-09-27 | Spain | Acceptable with conditions 2024-07-11
|
2024-09-27 |
| 3 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-07-08 | Spain | Acceptable 2025-09-09
|
2025-09-11 |
| 4 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2025-10-29 | Spain | Acceptable 2025-09-09
|
2025-10-29 |
| 5 | SUBSTANTIAL MODIFICATION | SM-3 | 2025-12-18 | Spain | Acceptable 2025-12-19
|
2025-12-19 |
| 6 | SUBSTANTIAL MODIFICATION | SM-4 | 2026-02-25 | Spain | Acceptable 2026-04-24
|
2026-04-24 |