Neoplasms
Conditions
Keywords
Adoptive T-cell therapy, Advanced synovial sarcoma, Advanced non-small cell lung cancer, Advanced tumors, GSK3845097, GSK3901961, GSK4427296, T cell receptors, Leukapheresis, Advanced myxoid/round cell liposarcoma
Brief summary
This trial will evaluate the safety and efficacy of first time in human engineered T-cell therapies, in participants with advanced tumors.
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).
Interventions
DRUGGSK3901961
GSK3901961 as an IV infusion.
DRUGGSK3845097
GSK3845097 as an IV infusion.
DRUGGSK4427296
GSK4427296 as an IV infusion.
DRUGCyclophosphamide
Cyclophosphamide will be used as lymphodepleting chemotherapy and will be administered via IV route.
DRUGFludarabine
Fludarabine will be used as lymphodepleting chemotherapy and will be administered via IV route.
Sponsors
Adaptimmune
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
This will be an open-label study. Hence, there will be no masking
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Enrolled Across Sub Studies | Day -7 | Number of Participants Randomized across sub studies are presented. |
Countries
Australia, Canada, Germany, Netherlands, Sweden, United States
Participant flow
Recruitment details
This master protocol study includes results data of screened participants for all the sub studies (NCT06048705 and NCT05943990). Results data is presented separately for 209012 Sub Study 1 (NCT06048705) and 209012 Sub Study 2 (NCT05943990). No participants were recruited for Sub Study 3. This is a master record and only contains data during screening phase (Day -35 to Day -8)
Pre-assignment details
This study and the sub studies associated were terminated due to a change in GSK's R&D priorities.
Participants by arm
| Arm | Count |
|---|---|
| Sub Study 1 (NCT06048705)-GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells Eligible participants were leukapheresed to manufacture engineered T cells. Participants then received 1 × 10\^9 - 8 × 10\^9 cells of GSK3901961 as an intravenous (IV) infusion in two aliquots (approximately 30% on Day 1 and approximately 70% on Day 8) for sentinel participant after completing lymphodepleting chemotherapy regimen that generally consisted of 30 milligram (mg)/meter (m)\^2/day fludarabine for 4 days (Day -7 to -4) and 900mg/ m\^2/day cyclophosphamide for 3 days (Day -6 to -4). | 1 |
| Sub Study 1 (NCT06048705) GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells Eligible participants were leukapheresed to manufacture engineered T cells. Participants then received 0.1 × 10\^9 - 0.8 × 10\^9 cells of GSK3901961 as an intravenous (IV) infusion on Day 1 after completing lymphodepleting chemotherapy regimen that generally consisted of 30 milligram (mg)/meter (m)\^2/day fludarabine for 4 days (Day -7 to -4) and 900mg/ m\^2/day cyclophosphamide for 3 days (Day -6 to -4). | 4 |
| Sub Study 1 (NCT06048705)-No Treatment No Treatment arm consisted of participants who underwent leukapheresis but did not go on to receive lymphodepletion chemotherapy and T cell infusion. | 2 |
| Sub Study 2 (NCT05943990)-GSK3845097 1 × 10^9 - 8 × 10^9 Transduced Cells Eligible participants were leukapheresed to manufacture engineered T cells. Participants then received 1 × 10\^9 - 8 × 10\^9 cells of GSK3845097 as an intravenous (IV) infusion in two aliquots (approximately 30% on Day 1 and approximately 70% on Day 8) for sentinel participants or all at once on Day 1 for all other participants after completing lymphodepleting chemotherapy regimen that generally consisted of 30 milligram (mg)/meter (m)\^2/day fludarabine for 4 days (Day -7 to -4) and 900mg/ m\^2/day cyclophosphamide for 3 days (Day -6 to -4). | 2 |
| Sub Study 2 (NCT05943990)-GSK3845097 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells Eligible participants were leukapheresed to manufacture engineered T cells. Participants then received 0.1 × 10\^9 - 0.8 × 10\^9 cells of GSK3845097 as an intravenous (IV) infusion on Day 1 after completing lymphodepleting chemotherapy regimen that generally consisted of 30 milligram (mg)/meter (m)\^2/day fludarabine for 4 days (Day -7 to -4) and 900mg/ m\^2/day cyclophosphamide for 3 days (Day -6 to -4). | 2 |
| Sub Study 2 (NCT05943990)-No Treatment No Treatment arm consists of participants who underwent leukapheresis but did not go on to receive lymphodepletion chemotherapy and T cell infusion. | 1 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Enrolled | Death prior to lymphodepletion | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Enrolled | Did not meet Inclusion/Exclusion Criteria | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Enrolled | Physician Decision | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Enrolled | Study Terminated by Sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Screening (Day -35 to Day -8) | HLA and NY-ESO-1 expression positive and did not enrol as met eligibility criteria but not needed | 3 | 0 | 0 | 0 | 0 | 0 | 0 |
| Screening (Day -35 to Day -8) | HLA and NY-ESO-1 expression positive and did not enrol due to physician decision | 4 | 0 | 0 | 0 | 0 | 0 | 0 |
| Screening (Day -35 to Day -8) | HLA and NY-ESO-1 expression positive and did not enrol due to withdrawal by participant | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Screening (Day -35 to Day -8) | HLA and NY-ESO-1 expression positive and did not meet inclusion/exclusion criteria | 6 | 0 | 0 | 0 | 0 | 0 | 0 |
| Screening (Day -35 to Day -8) | HLA and NY-ESO-1 expression positive but not enrol in the study due to study terminated by sponsor | 23 | 0 | 0 | 0 | 0 | 0 | 0 |
| Screening (Day -35 to Day -8) | Not tested for both HLA-type and NY-ESO-1 tumor expression | 40 | 0 | 0 | 0 | 0 | 0 | 0 |
| Screening (Day -35 to Day -8) | Tested for HLA-type and were HLA negative | 131 | 0 | 0 | 0 | 0 | 0 | 0 |
| Screening (Day -35 to Day -8) | Tested for NY-ESO-1 but not HLA-type and were NY-ESO-1 positive but not met other inclusion criteria | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Screening (Day -35 to Day -8) | Tested for NY-ESO-1 tumor expression but not HLA-type and were NY-ESO-1 negative | 9 | 0 | 0 | 0 | 0 | 0 | 0 |
| Screening (Day -35 to Day -8) | Tested HLA positive and were NY-ESO-1 Negative or Not Evaluable | 97 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Sub Study 1 (NCT06048705)-GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells | Sub Study 1 (NCT06048705) GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells | Sub Study 1 (NCT06048705)-No Treatment | Sub Study 2 (NCT05943990)-GSK3845097 1 × 10^9 - 8 × 10^9 Transduced Cells | Sub Study 2 (NCT05943990)-GSK3845097 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells | Sub Study 2 (NCT05943990)-No Treatment | Total |
|---|---|---|---|---|---|---|---|
| Age, Customized <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized 19-64 years | 1 Participants | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 10 Participants |
| Age, Customized >=65 years | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 4 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 1 Participants | 4 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 11 Participants |
| Region of Enrollment Australia | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Germany | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 5 Participants |
| Region of Enrollment Sweden | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Region of Enrollment United States | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 4 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Male | 0 Participants | 3 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Number of Participants Enrolled Across Sub Studies
Number of Participants Randomized across sub studies are presented.
Time frame: Day -7
Population: Screened Population includes all participants who signed an ICF to participate in the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Screened Participants | Number of Participants Enrolled Across Sub Studies | Sub Study 1 | 7 Participants |
| All Screened Participants | Number of Participants Enrolled Across Sub Studies | Sub Study 2 | 5 Participants |