This trial will evaluate safety, tolerability, and efficacy of letetresgene autoleucel (GSK3377794) with or without pembrolizumab in participants with relapsed and refractory multiple myeloma.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
6
Letetresgene autoleucel (GSK3377794) as an IV infusion
Letetresgene autoleucel (GSK3377794) as an IV infusion, followed by pembrolizumab every 3 weeks
Fludarabine will be used as lymphodepleting chemotherapy and will be administered via IV route.
GSK Investigational Site
Duarte, California, United States
GSK Investigational Site
Miami, Florida, United States
GSK Investigational Site
Tampa, Florida, United States
GSK Investigational Site
Atlanta, Georgia, United States
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a participant or clinical investigation participant who received a study treatment and the event need not necessarily have a causal relationship with study treatment. An SAE is any AE that results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in a persistent or significant disability; is a congenital anomaly/birth defect; is clinically significant or requires intervention to prevent one of the outcomes listed before.
Time frame: Up to 108 weeks
Number of Participants With Treatment Limiting Toxicities-GSK3377794+Pembrolizumab Arm Only
The following toxicities were considered to be treatment limiting toxicities: any \>=Grade 4 AE; Grade 3 non-infectious pneumonitis and any other Grade 3 AE (excluding pneumonitis), that did not improve to Grade 2 within 7 days after onset despite medical management and supportive care. Exceptions included the following: Grade 3 or 4 leukopenia, lymphopenia, neutropenia, or febrile neutropenia; Grade 3 or 4 thrombocytopenia not associated with significant bleeding; Grade 3 anemia; Grade 4 cytokine release syndrome (CRS) or toxicities related to CRS that resolved to Grade \<=2 within 7 days; other Grade 3 laboratory abnormality determined to be not clinically significant by the Investigator; Grade 3 or 4 fever and chills; Grade 3 or 4 hypoalbuminemia or abnormal electrolytes that responded to supplementation/correction; AE related to the cancer or its progression.
Time frame: Up to 3 weeks
Number of Participants With Worst-case Chemistry Results by Any Grade Increase Post-Baseline Relative to Baseline
Blood samples were collected for the assessment of following clinical chemistry parameters: glucose, albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, creatinine, potassium, magnesium, phosphate, sodium and calcium. Laboratory parameters were graded according to National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 4.03 where, Grade1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. An increase in grade is defined as an increase in CTCAE grade relative to Baseline grade. Data for any grade increase at worst case post Baseline is presented.
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Cyclophosphamide will be used as lymphodepleting chemotherapy and will be administered via IV route.
Pembrolizumab is available as an IV infusion
GSK Investigational Site
Baltimore, Maryland, United States
Time frame: Up to 108 weeks
Number of Participants With Worst-case Hematology Results by Any Grade Increase Post-Baseline Relative to Baseline
Blood samples were collected for the assessment of following hematology parameters: hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. Laboratory parameters were graded according to NCI-CTCAE version 4.03 where, Grade1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. An increase in grade is defined as an increase in CTCAE grade relative to Baseline grade. Data for any grade increase at worst case post Baseline is presented.
Time frame: Up to 108 weeks
Number of Participants With Worst-case Results for Coagulation Parameters Relative to Normal Range Post-Baseline Relative to Baseline
Blood samples were collected for the assessment of following coagulation parameters: prothrombin time and partial thromboplastin time (PTT). A laboratory value that is outside the normal range is considered either high abnormal (value above the upper limit of the normal range) or low abnormal (value below the lower limit of the normal range). Participants were counted twice if the participant had values in 'Decreased to low' and 'Increased to high' during the post-Baseline period. Data for worst case post Baseline is presented.
Time frame: Up to 108 weeks
Number of Participants With Worst-case Post Baseline Abnormal Electrocardiogram (ECG) Findings
ECG was recorded using an ECG machine that automatically calculated the heart rate and measured PR, RR, QRS and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Data for number of participants with abnormal clinically significant ECG findings for worst case post-Baseline has been presented. Clinically significant abnormal laboratory findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Time frame: Up to 108 weeks
Overall Response Rate
Overall response rate is defined as the percentage of participants with a best overall response (BOR) of confirmed stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) per International Myeloma Working Group (IMWG) Response Criteria (2016); where, PR: \>=50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>=90% or to \<200 milligrams (mg) per 24 hours; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \<100 mg per 24 hours; CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<= 5% plasma cells in bone marrow; or sCR: CR as defined by normal free light chain (FLC) ratio and absence of clonal cells by immunohistochemistry. Confidence intervals were calculated using the exact (Clopper-Pearson) method.
Time frame: Up to 108 weeks
Time to Response
Time to response is defined as the time interval (in months) from T-cell infusion to initial date of documented confirmed response (PR or better) in the subset of participants who showed a confirmed BOR of PR or better by Investigator assessment per IMWG (2016).
Time frame: Up to 108 weeks
Duration of Response
Duration of response is defined as the interval between the initial date of the confirmed response (sCR, CR, VGPR, or PR) and the initial assesment date of confirmed progressive disease or death among participants with a confirmed response per IMWG (2016).
Time frame: Up to 108 weeks
Progression-free Survival
Progression Free Survival is defined as the interval between the date of T-cell infusion and the initial assessment date of confirmed progressive disease as assessed by the investigator per IMWG (2016) or date of death. Progressive disease is defined as an increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>=0.5 grams per deciliter (g/dL); Serum M-protein increase \>=1 g/dL if the lowest M-component was \>=5 g/dL; Urinary M-protein (absolute increase must be \>=200 mg per 24 hours).
Time frame: Up to 108 weeks
Maximum Persistence (Cmax) of GSK3377794
Blood samples were collected to measure persistence of infused GSK3377794 using polymerase chain reaction of a vector specific sequence in deoxyribonucleic acid (DNA) extracted from peripheral blood mononuclear cell (PBMC).
Time frame: Up to 108 weeks
Time to Maximum Persistence
Blood samples were collected to measure persistence of infused GSK3377794 using polymerase chain reaction of a vector specific sequence in DNA extracted from PBMC.
Time frame: Up to 108 weeks
Area Under the Plasma Concentration-time Curve From Zero to Day 28 (AUC[0-28])
Blood samples were collected to measure persistence of infused GSK3377794 using polymerase chain reaction of a vector specific sequence in DNA extracted from PBMC.
Time frame: Up to Day 28