Neoplasms
Conditions
Keywords
GSK3377794, Pembrolizumab, T Cell Receptors, Adoptive T-cell therapy, Non-Small Cell Lung Cancer, Immuno-oncology, NY-ESO-1, LAGE-1a, Leukapheresis, Letetresgene autoleucel
Brief summary
This trial will evaluate safety and tolerability of letetresgene autoleucel (GSK3377794) with or without pembrolizumab in participants with non-small cell lung cancer.
Detailed description
New York esophageal squamous cell carcinoma-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 (GSK3377794) is the first generation of NY-ESO-1 specific T-cell receptor (TCR) engineered T-cells. This is a multi-arm, open-label study of letetresgene autoleucel (lete-cel, GSK3377794) in Human Leukocyte Antigen (HLA)-A\*02:01, HLA-A\*02:05 and/or HLA-A\*02:06 positive adults whose tumors express NY-ESO-1 and/or LAGE-1a. This study will enroll participants who have unresectable Stage IIIb or Stage IV NSCLC.
Interventions
DRUGLete-cel
lete-cel will be administered to eligible participants.
DRUGPembrolizumab
Pembrolizumab will be administered to eligible participants.
Sponsors
Merck Sharp & Dohme LLC
GlaxoSmithKline
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.
Intervention model description
Participants will receive GSK3377794, either as monotherapy or in combination with pembrolizumab.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>=18 years on the day of signing informed consent. * Histologically or cytologically diagnosed unresectable Stage IIIb or Stage IV NSCLC. * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. * Participant is positive for any of the following alleles: human leukocyte antigen (HLA)-A\*02:01, HLA-A\*02:05, and a) or HLA-A\*02:06 by a validated test. * Participant's tumor meets the pre-defined threshold for expression of NY-ESO-1 and/or LAGE-1a. * Adequate organ function and blood cell counts, as defined in the protocol. * Predicted life expectancy that is \>=24 weeks from leukapheresis. * Left ventricular ejection fraction \>=45%. * Prior therapies prior to lymphodepletion: a) All participants with NSCLC lacking actionable genetic aberrations, per National Comprehensive Cancer Network (NCCN) guidelines (Arms A and B), need to have received at least one line of programmed death protein 1/programmed death protein 1 ligand (PD-1/PD-L1) checkpoint blockade therapy. For participants in the metastatic setting, PD-1/PD-L1 checkpoint blockade therapy must have been received either alone, in combination or sequentially with platinum-containing chemotherapy. OR b) All participants with NSCLC with actionable genetic aberrations, per NCCN guidelines (Arm C only), should have received appropriate targeted therapy following NCCN or equivalent country-level guidelines. * Disease progression at time of treatment, as defined in the protocol. * Measurable disease at time of treatment per response evaluation criteria in solid tumors (RECIST) version 1.1 as assessed by local site investigator/radiology.
Exclusion criteria
* Prior treatment: 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. * Prior allogeneic/autologous bone marrow or solid organ transplantation. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide, fludarabine, dimethylsulfoxide (DMSO) or other agents used in the study. * Severe hypersensitivity (\>= Grade 3) to pembrolizumab and/or any of its excipients. * Active autoimmune disease that has required systemic treatment in past 2 years. * History of chronic or recurrent (within the last year prior to enrollment) severe autoimmune or active immune-mediated disease requiring steroids or other immunosuppressive treatments. * Uncontrolled intercurrent illness. * Participant has active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), Epstein Barr virus (EBV), cytomegalovirus (CMV), syphilis, or human T lymphotropic virus (HTLV), as defined in protocol. * Known psychiatric or substance abuse disorders. * Symptomatic or untreated central nervous system (CNS) metastases. * Radiotherapy that involves the lung (Percentage of normal lung receiving at least 20 Gray \[Gy\] during radiotherapy \[V20\] exceeding 30% lung volume or mean heart dose \>20 Gy) within 3 months or radiotherapy (including but not limited to palliative radiotherapy) to lung/mediastinum with V20 less than 30% lung volume and with mean heart dose \<=20 Gy within 4 weeks (+/- 3 days). * Radiotherapy of \>=50 Gy to a significant volume of the pelvis, long bones or spine, or a cumulative dose of radiation that, in the investigator's opinion would predispose participants to prolonged cytopenia after lymphodepletion. * All of the participant's measurable lesions have been irradiated within 3 months before lymphodepletion. * Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to approximately 10 months | An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations which involve medical or scientific judgment or is associated with liver injury and impaired liver function. AEs which start or worsen on or after T-cell infusion are defined as treatment-emergent. |
| Number of Participants With Treatment-emergent Adverse Events of Special Interest (AESI) | Up to approximately 10 months | AESI included cytokine release syndrome (CRS), pneumonitis/pneumonia, graft vs host disease (GvHD), guillain barre syndrome (GBS) or acute inflammatory demyelinating polyneuropathy (AIDP), pancytopenia/aplastic anemia (including analysis of all hematopoietic cytopenias), immune effector cell-associated neurotoxicity syndrome (ICANS) and treatment-related inflammatory response at tumor site. AEs which start or worsen on or after T-cell infusion are defined as treatment-emergent. |
| Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events Based on Maximum Severity Grades | Up to approximately 10 months | An AE is any untoward medical occurrence in a clinical investigation, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations which involve medical or scientific judgment or is associated with liver injury and impaired liver function. AEs which start or worsen on or after T-cell infusion are defined as TE. Severity was reported during study and was assigned a grade according to the National Institutes of Health National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). SAEs are subset of AEs. AEs and SAEs severity graded on a 5-point scale as: 1 = mild, 2 = moderate discomfort, 3 = severe, 4 = life-threatening and 5 = death due to AE. |
| Number of Participants With AEs Leading to Dose Delays | Up to approximately 10 months | An AE is any untoward medical occurrence in a clinical investigation, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with AEs leading to dose delays were summarized. |
| Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | Up to approximately 10 months | Overall response rate (ORR) defined as the percentage of participants with a complete response (CR) or partial response (PR) via investigator assessment per RECIST (Response Evaluation Criteria in Solid Tumors Criteria) v1.1 relative to the total number of participants in the analysis population. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeters (mm). Confidence intervals (CI) were calculated using the exact (Clopper-Pearson) method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Cmax (Tmax) of Lete-cel | Day 1 to Day 15 | Tmax was defined as time to reach peak cell expansion during the study. Blood samples were collected for analysis of Tmax of lete-cel. |
| Progression-free Survival (PFS) Per RECIST Version 1.1 by Investigator Assessment | Up to approximately 10 months | Progression free survival was defined as the interval between the date of T cell infusion and the earliest date of disease progression or death due to any cause. Progressive disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. PFS based on responses assessed by investigator per RECIST v1.1 is presented. Kaplan-Meier Median and 95% confidence intervals are presented. Confidence intervals were calculated using the Brookmeyer-Crowley method. |
| Area Under the Plasma Concentration-time Curve to Day 28 (AUC0-28d) of Lete-cel | Up to 28 days | Area under the cell expansion-time curve from first T-cell infusion to Day 28. Blood samples were collected to measure AUC (0-28 days). |
| Disease Control Rate (DCR) Per RECIST Version 1.1 by Investigator Assessment | Up to approximately 10 months | DCR was defined as the percentage of participants with a confirmed complete response (CR), partial response (PR), or stable disease (SD) for at least 6 months as per RECIST v1.1. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeters (mm). SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Confidence intervals (CI) were calculated using the exact (Clopper-Pearson) method. |
| Duration of Response (DOR) Per RECIST Version 1.1 by Investigator Assessment | Up to approximately 10 months | Duration of response was defined as the interval between the initial date of confirmed response (PR/CR) and the date of progressive disease or death among participants with a confirmed response per RECIST 1.1. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeters. |
| Time to Response (TTR) Per RECIST Version 1.1 by Investigator Assessment | Up to approximately 10 months | Time to response was defined as the interval of time between the date of T-cell infusion and the first documented evidence of the confirmed response (PR or CR), in the subset of participants with a confirmed PR or CR as their best confirmed overall response. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 mm. |
| Maximum Transgene Expansion (Cmax) of Lete-cel | Day 1 to Day 15 | Cmax was defined as peak cell expansion during the study. Blood samples were collected for analysis of Cmax of lete-cel. |
Countries
Canada, Netherlands, Spain, United Kingdom, United States
Participant flow
Recruitment details
This was an open-label study that evaluated the safety and tolerability of autologous T-cells expressing enhanced T-cell receptors (TCRs) that were specific for New York esophageal squamous cell carcinoma (NY-ESO)-1 and/or Cancer testis antigen 2 (LAGE-1a) (GSK3377794, Lete-cel) in participants with Advanced or Recurrent Non-Small Cell Lung Cancer who had Human Leukocyte Antigen (HLA)-A02:01, HLA-A02:05, and/or HLA-A\*02:06.
Pre-assignment details
A total of 34 participants were enrolled in this study, out of which 13 received Lete-cel infusion. The study was terminated due to reasons pertaining to feasibility As a result of the early termination, no participants were assigned to Arm B, and thus no analysis of Arm B was performed.
Participants by arm
| Arm | Count |
|---|---|
| Arm A: Lete-cel Monotherapy Eligible participants underwent leukapheresis to manufacture autologous T cells bearing T- cell receptors (TCR) specific for NY-ESO-1/LAGE-1a. Lymphodepleting chemotherapy was administered, consisting of cyclophosphamide at a dose of 900 mg/m\^2/day on day -7 through day -5 and fludarabine at a dose of 30 mg/m\^2/day on day -8 through day -5. On day 1, participants received a single infusion of Lete-cel. Participants who had disease progression within 25 weeks of Lete-cel infusion were offered therapy with Pembrolizumab following benefit-risk evaluation. Pembrolizumab 200 mg was administered every three weeks (Q3W) for up to 35 cycles (up to Week 106) or until subsequent disease progression or intolerable toxicity. Pembrolizumab therapy was not allowed if disease progression occurred post 25 weeks of Lete-cel infusion. | 20 |
| Arm C: Lete-cel + Pembrolizumab Eligible participants underwent leukapheresis to manufacture autologous T cells bearing T-cell receptors (TCR) specific for NY-ESO-1 /LAGE-1a. Lymphodepleting chemotherapy was administered, consisting of cyclophosphamide at a dose of 900 mg/m\^2/day on day -7 through day -5 and fludarabine at a dose of 30 mg/m\^2/day on day -8 through day -5. On day 1, participants received a single infusion of Lete-cel followed by pembrolizumab 200 mg starting on Day 22 (Week 4 Day 1). Pembrolizumab was administered every three weeks (Q3W) for up to 35 cycles (up to Week 106) or until disease progression, whichever occurred first. | 14 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Death Prior to Lete-cel Infusion | 1 | 1 |
| Overall Study | Physician Decision | 14 | 8 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Arm A: Lete-cel Monotherapy | Arm C: Lete-cel + Pembrolizumab | Total |
|---|---|---|---|
| Age, Continuous | 62.1 YEARS STANDARD_DEVIATION 8.9 | 59.4 YEARS STANDARD_DEVIATION 10.25 | 61.0 YEARS STANDARD_DEVIATION 9.42 |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 19 Participants | 12 Participants | 31 Participants |
| Sex: Female, Male Female | 8 Participants | 9 Participants | 17 Participants |
| Sex: Female, Male Male | 12 Participants | 5 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 7 | 1 / 6 | 5 / 21 |
| other Total, other adverse events | 7 / 7 | 6 / 6 | 3 / 21 |
| serious Total, serious adverse events | 5 / 7 | 4 / 6 | 2 / 21 |
Outcome results
Primary
Number of Participants With AEs Leading to Dose Delays
An AE is any untoward medical occurrence in a clinical investigation, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with AEs leading to dose delays were summarized.
Time frame: Up to approximately 10 months
Population: Modified intent-to-treat (mITT) population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: Lete-cel Monotherapy | Number of Participants With AEs Leading to Dose Delays | 1 Participants |
| Arm C: Lete-cel + Pembrolizumab | Number of Participants With AEs Leading to Dose Delays | 1 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations which involve medical or scientific judgment or is associated with liver injury and impaired liver function. AEs which start or worsen on or after T-cell infusion are defined as treatment-emergent.
Time frame: Up to approximately 10 months
Population: Modified Intent-to-Treat (mITT) population included all participants who received Lete-cel infusion.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: Lete-cel Monotherapy | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 7 Participants |
| Arm A: Lete-cel Monotherapy | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 5 Participants |
| Arm C: Lete-cel + Pembrolizumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 6 Participants |
| Arm C: Lete-cel + Pembrolizumab | Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 3 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events Based on Maximum Severity Grades
An AE is any untoward medical occurrence in a clinical investigation, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations which involve medical or scientific judgment or is associated with liver injury and impaired liver function. AEs which start or worsen on or after T-cell infusion are defined as TE. Severity was reported during study and was assigned a grade according to the National Institutes of Health National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). SAEs are subset of AEs. AEs and SAEs severity graded on a 5-point scale as: 1 = mild, 2 = moderate discomfort, 3 = severe, 4 = life-threatening and 5 = death due to AE.
Time frame: Up to approximately 10 months
Population: Modified intent-to-treat (mITT) population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: Lete-cel Monotherapy | Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events Based on Maximum Severity Grades | AEs, Grade 4 | 5 Participants |
| Arm A: Lete-cel Monotherapy | Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events Based on Maximum Severity Grades | SAEs, Grade 3 | 4 Participants |
| Arm A: Lete-cel Monotherapy | Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events Based on Maximum Severity Grades | AEs, Grade 3 | 1 Participants |
| Arm A: Lete-cel Monotherapy | Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events Based on Maximum Severity Grades | SAEs, Grade 4 | 1 Participants |
| Arm A: Lete-cel Monotherapy | Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events Based on Maximum Severity Grades | AEs, Grade 5 | 0 Participants |
| Arm A: Lete-cel Monotherapy | Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events Based on Maximum Severity Grades | SAEs, Grade 5 | 0 Participants |
| Arm A: Lete-cel Monotherapy | Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events Based on Maximum Severity Grades | AEs, Grade 2 | 1 Participants |
| Arm C: Lete-cel + Pembrolizumab | Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events Based on Maximum Severity Grades | SAEs, Grade 5 | 1 Participants |
| Arm C: Lete-cel + Pembrolizumab | Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events Based on Maximum Severity Grades | AEs, Grade 2 | 0 Participants |
| Arm C: Lete-cel + Pembrolizumab | Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events Based on Maximum Severity Grades | AEs, Grade 3 | 3 Participants |
| Arm C: Lete-cel + Pembrolizumab | Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events Based on Maximum Severity Grades | AEs, Grade 4 | 2 Participants |
| Arm C: Lete-cel + Pembrolizumab | Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events Based on Maximum Severity Grades | AEs, Grade 5 | 1 Participants |
| Arm C: Lete-cel + Pembrolizumab | Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events Based on Maximum Severity Grades | SAEs, Grade 3 | 2 Participants |
| Arm C: Lete-cel + Pembrolizumab | Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events Based on Maximum Severity Grades | SAEs, Grade 4 | 0 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events of Special Interest (AESI)
AESI included cytokine release syndrome (CRS), pneumonitis/pneumonia, graft vs host disease (GvHD), guillain barre syndrome (GBS) or acute inflammatory demyelinating polyneuropathy (AIDP), pancytopenia/aplastic anemia (including analysis of all hematopoietic cytopenias), immune effector cell-associated neurotoxicity syndrome (ICANS) and treatment-related inflammatory response at tumor site. AEs which start or worsen on or after T-cell infusion are defined as treatment-emergent.
Time frame: Up to approximately 10 months
Population: Modified Intent to Treat (mITT) population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: Lete-cel Monotherapy | Number of Participants With Treatment-emergent Adverse Events of Special Interest (AESI) | 6 Participants |
| Arm C: Lete-cel + Pembrolizumab | Number of Participants With Treatment-emergent Adverse Events of Special Interest (AESI) | 6 Participants |
Primary
Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment
Overall response rate (ORR) defined as the percentage of participants with a complete response (CR) or partial response (PR) via investigator assessment per RECIST (Response Evaluation Criteria in Solid Tumors Criteria) v1.1 relative to the total number of participants in the analysis population. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeters (mm). Confidence intervals (CI) were calculated using the exact (Clopper-Pearson) method.
Time frame: Up to approximately 10 months
Population: Modified intent-to-treat (mITT) population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: Lete-cel Monotherapy | Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | 0 Percentage of Participants |
| Arm C: Lete-cel + Pembrolizumab | Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | 0 Percentage of Participants |
Secondary
Area Under the Plasma Concentration-time Curve to Day 28 (AUC0-28d) of Lete-cel
Area under the cell expansion-time curve from first T-cell infusion to Day 28. Blood samples were collected to measure AUC (0-28 days).
Time frame: Up to 28 days
Population: Pharmacokinetic (PK) population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A: Lete-cel Monotherapy | Area Under the Plasma Concentration-time Curve to Day 28 (AUC0-28d) of Lete-cel | 1646416.5835 Days*copies per microgram genomic DNA | Geometric Coefficient of Variation 109.45757 |
| Arm C: Lete-cel + Pembrolizumab | Area Under the Plasma Concentration-time Curve to Day 28 (AUC0-28d) of Lete-cel | 1565617.646 Days*copies per microgram genomic DNA | Geometric Coefficient of Variation 46.16918 |
Secondary
Disease Control Rate (DCR) Per RECIST Version 1.1 by Investigator Assessment
DCR was defined as the percentage of participants with a confirmed complete response (CR), partial response (PR), or stable disease (SD) for at least 6 months as per RECIST v1.1. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeters (mm). SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Confidence intervals (CI) were calculated using the exact (Clopper-Pearson) method.
Time frame: Up to approximately 10 months
Population: Modified intent-to-treat (mITT) population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: Lete-cel Monotherapy | Disease Control Rate (DCR) Per RECIST Version 1.1 by Investigator Assessment | 0 Percentage of Participants |
| Arm C: Lete-cel + Pembrolizumab | Disease Control Rate (DCR) Per RECIST Version 1.1 by Investigator Assessment | 0 Percentage of Participants |
Secondary
Duration of Response (DOR) Per RECIST Version 1.1 by Investigator Assessment
Duration of response was defined as the interval between the initial date of confirmed response (PR/CR) and the date of progressive disease or death among participants with a confirmed response per RECIST 1.1. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeters.
Time frame: Up to approximately 10 months
Population: Modified intent-to-treat (mITT) population. Only participants with CR or PR were included in the analysis. No participant achieved CR or PR, hence the number of participants analyzed is 0.
Secondary
Maximum Transgene Expansion (Cmax) of Lete-cel
Cmax was defined as peak cell expansion during the study. Blood samples were collected for analysis of Cmax of lete-cel.
Time frame: Day 1 to Day 15
Population: Pharmacokinetic (PK) population included all participants in the mITT population from whom at least one PK sample was obtained, analyzed, and was measurable.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A: Lete-cel Monotherapy | Maximum Transgene Expansion (Cmax) of Lete-cel | 155712.1398 Copies per microgram genomic DNA | Geometric Coefficient of Variation 55.21519 |
| Arm C: Lete-cel + Pembrolizumab | Maximum Transgene Expansion (Cmax) of Lete-cel | 127343.0679 Copies per microgram genomic DNA | Geometric Coefficient of Variation 34.95574 |
Secondary
Progression-free Survival (PFS) Per RECIST Version 1.1 by Investigator Assessment
Progression free survival was defined as the interval between the date of T cell infusion and the earliest date of disease progression or death due to any cause. Progressive disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. PFS based on responses assessed by investigator per RECIST v1.1 is presented. Kaplan-Meier Median and 95% confidence intervals are presented. Confidence intervals were calculated using the Brookmeyer-Crowley method.
Time frame: Up to approximately 10 months
Population: Modified intent-to-treat (mITT) population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Lete-cel Monotherapy | Progression-free Survival (PFS) Per RECIST Version 1.1 by Investigator Assessment | 5.32 Months |
| Arm C: Lete-cel + Pembrolizumab | Progression-free Survival (PFS) Per RECIST Version 1.1 by Investigator Assessment | 1.48 Months |
Secondary
Time to Cmax (Tmax) of Lete-cel
Tmax was defined as time to reach peak cell expansion during the study. Blood samples were collected for analysis of Tmax of lete-cel.
Time frame: Day 1 to Day 15
Population: Pharmacokinetic (PK) population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Lete-cel Monotherapy | Time to Cmax (Tmax) of Lete-cel | 3 Days |
| Arm C: Lete-cel + Pembrolizumab | Time to Cmax (Tmax) of Lete-cel | 7.9 Days |
Secondary
Time to Response (TTR) Per RECIST Version 1.1 by Investigator Assessment
Time to response was defined as the interval of time between the date of T-cell infusion and the first documented evidence of the confirmed response (PR or CR), in the subset of participants with a confirmed PR or CR as their best confirmed overall response. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 mm.
Time frame: Up to approximately 10 months
Population: Modified intent-to-treat (mITT) population. Only participants with CR or PR were included in the analysis. No participant achieved CR or PR, hence the number of participants analyzed is 0.